MXPA06005364A

MXPA06005364A - Quinazoline derivatives

Info

Publication number: MXPA06005364A
Application number: MXPA/A/2006/005364A
Authority: MX
Inventors: Hugh Bradbury Robert; Grant Kettle Jason; Francois Andre Hennequin Laurent
Original assignee: Astrazeneca Ab
Priority date: 2003-11-13
Filing date: 2006-05-12
Publication date: 2006-10-17

Abstract

wherein the substituents are as defined in the text for use in the production of an anti proliferative effect which effect is produced alone or in part by inhibiting erbB2 receptor tyrosine kinase in a warm-blooded animal such as man.

Description

QU1NAZOLINE DERIVATIVES The invention relates to certain novel quinazoline derivatives, or pharmaceutically acceptable salts thereof, which possess anti-tumor activity and according to the above are useful in methods of processing the animal or human body. The invention also relates to processes for the manufacture of said quinazoline derivatives, to pharmaceutical compositions containing them and to their use in therapeutic methods, for example in the manufacture of medicaments for use in the prevention or framagement of solid tumor disease in a warm-blooded animal, such as a human. Many of the current trafficking regimes for diseases resulting from the abnormal regulation of cell proliferation such as psoriasis and cancer, use compounds that inhibit DNA synthesis and cell proliferation. To date, the compounds used in such treatments are generally toxic to cells, however their improved effects in rapidly dividing cells such as tumor cells can be beneficial. Alternate approaches to these cytotoxic anti-tumor agents are currently being developed, for example, selective inhibitors of cell signaling pathways. These types of inhibitors probably have the potential to display enhanced selectivity of action against tumor cells and probably reduce the likelihood of therapy having desirable side effects. Eukaryotic cells continuously respond to many diverse extracellular signals that allow communication between cells in an organism. These signals regulate a wide variety of physical responses in the cell including proliferation, differentiation, apoptosis and motility. Extracellular signals take the form of a diverse variety of soluble factors including growth factors as well as paracrine and endocrine facies. By binding to specific transmembrane receptfores, these ligands integrate the extracellular signal into the intracellular signaling pathways, thus translating the signal through the plasma membrane and allowing the individual cell to respond to its extracellular signals. Many of these signal transduction processes utilize the reversible process of phosphorylation of proteins that are included in the promotion of these diverse cellular responses. The phosphorylation status of target proteins is regulated by specific kinases and phosphatases that are responsible for the regulation of approximately one-third of all proteins encoded by the mammalian genome. Since phosphorylation is an important regulatory mechanism in the signal transduction process, it is therefore not surprising that the aberrations in these in-cell pathways resulfan in abnormal cell growth and differentiation and thus promote cellular transformation (reviewed in Cohen et al, Curr. Opin Chem Biol, 1 999, 3, 459-465).

It has been amply shown that a number of these tyrosine kinases are mutated in substantially acidic forms and / or when they are overexpressed in the transformation of a variety of human cells. These are mutated and over-expressed forms of the kinase splan present in a large proportion of human tumors (reviewed in Kolibaba ef al, Biochimica et Biophysica Acta, 1997, 133, F217-F248). As tyrosine kinases play key roles in the proliferation and differentiation of a variety of tissues, much focus has focused on these enzymes in the development of new anti-cancer therapies. This family of enzymes is divided into two groups - receptor and non-receptor tyrosine kinases, for example, EGF Receptors and the SRC family, respectively. From the results of a large number of studies including the Human Genome Projection, approximately 90 tyrosine kinases have been identified in the human genome, of these 58 are of the receptor type and 32 are of the non-receptor type. These can be seen on 20 receptor tyrosine kinases and 1 0 non-receptor tyrosine kinase sub-families (Robinson et al., Oncogene, 2000, 19, 5548-5557). Tyrosine receptor kinases are of particular importance in the transmis of mitogenic signals that initiate cellular replication. Large glycoprotein spheres, which expand the plasma membrane of the cell possess an exfracellular binding domain for their specific ligands (such as Epidermal Growth Factor (EGF) for the EGF Receptor). The binding of the ligand resulted in the activation of the enzymatic activity of kinase - of the receptor that is encoded by the intracellular portion of the receptor.

This activity phosphorylates the key tyrosine amino acids in target proteins, resulting in the transduction of proliferative signals through the plasma membrane of the cell. It is known that the erbB family of receptor tyrosine kinases, including EGFR, erbB2, erbB3 and erbB4, are frequently included in triggering the proliferation and survival of tumor cells (reviewed in Olayioye et al. EMBO J., 2000, 19 ., 3159). A mechanism in which this can be done is by overexpression of the receptor at the prolein level, usually as a result of genetic amplification. This has been observed in many common human cancers (reviewed in Klapper et al., Adv. Cancer Res., 2000,77., 25) such as breast cancer (Sainsbury et al. Brit. J. Cancer, 1988, 58, 458; Guerin et al .. Oncoqene Res., 1 988.3.21; Slamon et al., Science, 1989, 244, 707; Klijn et al. Breast Cancer Res. Treaí., 1994,29., 73 and reviewed in Solomon et al., Crit. Rev. Oncol. Hematol., 1 995,19., 1 83), non-small cell lung cancers (NSCLCs) including adenocarcinomas (Cerny et al. Brit. J. Cancer, 1 986.54.265; Reubi et al., Int.J. Cancer, 1 990.45, 269; Rusch et al., Cancer Research, 1 993.53, 2379; Brabender et al., Clin. Cancer Res. ., 2001, 7, 1 850) as well as other lung cancers (Hendler et al .. Cancer Cells, 1989,7, 347; Ohsaki et al .. Oncol. Rep. 2000,7, 603), cancer bladder (Neal et al., Lancet, 1 985, 366; Chow et al., Clin Cancer Res., 2001, 7, 1 957, Zhau et al. Mol Carcinog., 3, 254), oesophageal cancer (Muka ida et al., Cancer, 1991, 68, 142), gastrointestinal cancer such as colon, rectal or esomeomacal cancer (Bolen et al., Oncoqene Res., 1987,1, 149; Kapitanovic et al., Gastroeníerology, 2000,112, 1103; Ross et al., Cancer Invest., 2001, 9, 554), cancer of the prostate (Visakorpi et al., Histochem J., 1992, 241, 481; Kumar et al., 2000, 32, 73; Scher et al. al .. J. Nati, Cancer lnst., 2000,92, 1866), leukemia (Konaka et al. Cell, 1984,37, 1035, Martin-Subero et al .. Cancer Geneí Cyíogeneí., 2001, 127,174), ovarian cancer (Hellsfrom et al .. Cancer Res., 2001, (31, 2420), head and neck (Shiga et al., Head Neck, 2000,22, 599) or pancreatic (Ovotny et al .. Neoplasm, 2001,48, 188) As more human tumor tissues are tested for expression of the erbB family of receptor tyrosine kinases it is expected that their widespread prevalence and importance will be further increased in the future as a consequence of poor regulation of one or more of these receptors (in particular erbB2), it is widely believed that many tumors become clinically more aggressive and thus correlate with a poorer prognosis for the patient (Brabender et al., Clin. Cancer Res., 2001 , 7, 1850; Ross et al., Cancer Investiqation, 2001,19., 554, Yu et al., Bioessavs, 2000,22,7,673). In addition to these clinical discoveries, a wealth of pre-clinical information suggests that the erbB family of receptor tyrosine kinases are included in cell transformation. This includes observations that many cell lines overexpress one or more of the erbB receptors and that EGFR and erbB2 when transfected into non-fuming cells have the ability to transform these cells. This polymorphism has also verified that transgenic raffones that overexpress erbB2 spontaneously develop tumors in the mammary gland. In addition to this, a number of pre-clinical studies have shown that anti-proliferative effects can be induced by knocking out one or more erbB acivivities by small molecule inhibitors, inhibitory anbodies or dominant negatives (reviewed in Mendelsohn et al .. Oncoqene, 2000, 19, 6550). Thus it has been recognized that inhibitors of these receptor tyrosine kinases should be of value as a selective inhibitor of the proliferation of mammalian cancer cells (Yaish et al., Science, 1988,242,933, Kolibaba et al, Biochimica et Biophysica Acia, 1 997, 133, F21 7-F248; Al-Obeidi ef al, 2000, Qncoqene, 1 9.5690-5701; Mendelsohn et al, 2000, Oncoqene, 1, 9.6550-6565). In addition to pre-clinical daphne sequences, discoveries using inhibitory antibodies against EGFR and erbB2 (c-225 and trastuzumab respectively) have proven to be beneficial in the clinic for the screening of selected solid tumors (reviewed in Mendelsohn et al, 2000, Oncoqene , 1, 9.6550-6565). Amplification and / or activity of members of tyrosine receptor kinases of ErbB type have been detected and thus have been implicated to play a role in a number of non-malignant proliferative disorders such as psoriasis (Ben-Bassat, Curr. Pharm. Des., 2000 , 6, 933; Eider et al., Science, 1 989,243.81 1), benign prostatic hyperplasia (BPH) (Kumar et al., Int. Urol. Nephrol., 2000,32,73), atherosclerosis and restenosis (Bokemeyer et al., Kidnev Int., 2000, 58., 549). Therefore, it is expected that inhibitors of erbB receptor tyrosine kinases will be useful in the trafficking of cells and other non-malignant disorders of excessive cell proliferation. International Patent Applications WO 96/09294, WO 96/1 51 18, WO 96/1 6960, WO 96/30347, WO 96/33977, WO 96/33978, WO 96/33979, WO 96/33980, WO 96 / 33981, WO 97/03069, WO 97/13771, WO 97/30034, WO 97/30035, WO 97/38983, WO 98/02437, WO 98/02434, WO 98/02438, WO 98/13354, WO 99 / 35132, WO 99/35146, WO 01/21 596, WO 01/55141 and WO 02/1 8372 disclose that quinazoline derivatives which compare an anilino substituent in the 4-position possess receptor tyrosine kinase inhibitory activity. The International Patent Applications WO 97/22596 and WO 98/13354 disclose that certain 4-anilinoquinazoline derivatives which are substituted in the 7-position are VEGF inhibitors or mixed receptor tyrosine kinase inhibitors VEGF / EGF. The anilino group in these applications is substituted with small groups such as halogen or alkyl (1 -3C). International Patent Application WO 01/94341 discloses that certain quinazoline derivatives which are substituted in the 5-position are inhibitors of the Src family of non-receptor tyrosine kinases, such as c-Src, c-Yes and c-Fyn. There are no descriptions in WO 01/94341 of 4-anilinoquinazolines wherein the aniline group is subsumed in the para position by a substituent containing an aryl or a heteroaryl group. International Patent Applications WO 03/0401 08 and WO 03/0401 09 disclose that certain substiuuted 5-quinazoline derivatives are inhibitors of the erbB family of tyrosine kinase inhibitors, particularly receptor tyrosine kinases, particularly EGFR and erb-B2. All compounds in these applications carry a ring containing substituent at the 5-position on the quinazoline ring. None of the above techniques describe 4-anilinoquinazolines which are substituted in the 5-position by an acylaminoethoxy group and which carries an aryl or heteroaryl containing substituent in the para-position in the aniline ring. We have now found that, surprisingly, the quinazoline derivatives substi tuted at position 5 with a subsitute containing an acylaminoethoxy group possesses pyrimetic acid activity. Without wishing to imply that the compounds described in the present invention possess pharmacological acfivity solely by virtue of an effect on a single biological process, it is believed that the compounds provide an anti-tumor effect by way of inhibition of one or more of the erbB family of receptor tyrosine kinases that are included in the signal transduction steps that lead to the proliferation of tumor cells. In particular, it is believed that the compounds of the present invention provide an effecfo anífumor in the manner of inhibition of EGFR and / or erbB2 receptor firosin kinases. Generally, the compounds of the present invention possess potent inhibitory activity confers the erbB receptor tyrosine kinase family, for example by inhibition of receptor tyrosine kinases EGFR and / or erbB2 and / or erbB4, while possessing less potent inhibitory activity than other kinases. . In addition, generally the compounds of the present invention possess substantially better susceptibility against erbB2 over that of the EGFR tyrosine kinase, thus potentially providing effective targeting for tumors driven by erbB2. Accordingly, it may be possible to administer a compound according to the present invention in a dose that is sufficient to inhibit erbB2 tyrosine kinase while not having a significant effect on EGFR (or other) írosine kinases. The selective inhibition provided by the compounds according to the present invention can provide treatments for erbB2 tyrosine kinase mediated conditions, while reducing the undesirable side effects that may be associated with the inhibition of other tyrosine kinases. Generally, the compounds according to the invention also show favorable DMPK properties, for example at the bioavailability, and favorable physical properties fa as solubility. In addition, many of the compounds according to the present invention are inactive and only weakly active in a hERG assay.

According to a first aspect of the invention, a quinazoline derivative of the formula I is provided: wherein: m is 0, 1 or 2; each R1, which may be the same or different, is selected from hydroxy, alkoxy (1-6C), cycloalkyl (3-7C) -oxi and cycloalkyl (3-7C) -alkoxy (1 -6C), and wherein any CH2 or CH3 group in a substituent R1 optionally carries in each of said group CH2 or CH3 one or more substituents of alkyl (1-6C) or halogen, or a substituent selected from hydroxy and alkoxy (1-6C), R2 is hydrogen or alkyl (1-4C); n is 0, 1, 2, 3 or 4; each R3, which may be the same or different, is selected from cyano, halogen, alkyl (1-4C), trifluoromethyl, alkoxy (1-4C), alkenyl (2-4C) and alkynyl (2-4C); X1 is selected from O, S, SO, SO2, N (R7), CH (OR7), CON (R7), N (R7) CO, SO2N (R7), N (R7) SO2, OC (R7) 2, C (R7) 2O, SC (R7) 2, C (R7) 2S, CO, C (R7) 2N (R7) and N (R7) C (R7) 2, wherein each R7, which may be the same or different, is hydrogen or alkyl (1-6C); Q1 is aryl, or heteroaryl, and wherein Q1 optionally bears one or more substituents (for example 1, 2 or 3), which may be the same or different, selected from halogen, cyano, nitro, hydroxy, amino, carboxy, carbamoyl , sulfamoyl, formyl, mercapto, alkyl (1-6C), alkenyl (2-8C), alkynyl (2-8C), alkoxy (1-6C), alkenyloxy (2-6C), alkynyloxy (2-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, alkoxycarbonyl (1-6C), N-alkylcarbamoyl (1-6C), N, N-di- [(1-6C) alkyl] carbamoyl, (2-6C) alkanoyl, (3-6C) alkenoyl, (3-6C) alkynyl, (2-6C) alkanoyloxy, alkanoylamino (2-6C), N-alkyl (1-6C) -alkylamino (2-6C), alkenoylamino (3-6C), N-alkyl (1-6C) -alkenoylamino (3-6C), alkynylamino (3-) 6C), N-alkyl (1-6C) -alkynylamino (3-6C), ___-alkylsulfamoyl (1-6C), j __., N.-di- [alkyl (1-6C)] sulfamoyl, alkanesulfonylamino (1 -6C), N.-alkyl (1-6C) -alkanesulfonylamino (1-6C) and a group of the formula: -X2-R8 wherein X2 is an direct link or is selected from O, CO and N (R9), wherein R9 is hydrogen or alkyl (1-6C), and R8 is halo-alkyl (1-6C), hydroxy-alkyl (1-6C), carboxy -alkyl (1-6C), alkoxy (1-6C) -alkyl (1-6C), cyano-alkyl (1-6C), amino-alkyl (1-6C), N-alkylamino (1-6C) -alkyl (1-6C), JN, _N.-di [alkyl (1-6C)] amino-alkyl (1-6C), alkanoylamino (2-6C) -alkyl (1-6C), N-alkyl (1) -6C) -alkylamino (2-6C) -alkyl (1-6C), alkoxycarbonylamino (1-6C) -alkyl (1-6C), carbamoyl-alkyl (1-6C), N-alkylcarbamoyl (1-6C) - alkyl (1-6C), N, N-di [(1-6C) alkyl] carbamoylalkyl (1-6C), alkylthio (1-6C) -alkyl (1-6C), alkylsulfinyl (1-6C) -alkyl (1-6C), alkylsulfonyl (1-6C) -alkylsulfamoyl (1-6C) alkyl (1-6C), N-alkylsulfamoyl (1-6C) alkyl (1-6C), (1-6C) alkyl ( 1 -6C), alkanoyl (2-6C) -alkyl (1-6C), alkanoyloxy (2-6C) -alkyl (1-6C) or alkoxycarbonyl (1-6C) -alkyl (1-6C), and wherein any group CH2 or CH3 in -X1-Q1 optionally carries in each said group CH2 or CH3 one or more (for example 1, 2, or 3) halogen substituents or alkyl (1-6C) or a substituent selected from hydroxy, cyano, amino, alkoxy (1-4C), alkylamino (1-4C) and di- [alkylamino (1-4C)]; R4, R4a, R5 and R5a, which may be the same or different, are selected from hydrogen and alkyl (1-6C), or R4 and R4a together with the carbon atom to which they are attached form a cycloalkyl ring (3- 7C), or R5 and R5a together with the carbon atom to which they are attached form a cycloalkyl (3-7C) ring, and wherein any CH2 or CH3 group in any of R4, R4a, R5 and R5a optionally bears in each said CH2 or CH3 group one or more (for example 1, 2 or 3) halogen substituents or a substituent selected from hydroxy, cyano, (1-6C) alkoxy, amino, (2-6C) alkanoyl, (1-6C) alkylamino and di- [alkylamino (1-6C)]; R6 is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C), cycloalkenyl ( 3-7C), cycloalkenyl (3-7C) -alkyl (1-6C), heterocyclyl and heterocyclyl-alkyl (1-6C), and wherein any heterocyclyl group in a R6 substituent optionally carries one or more substituents, which can be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C) ), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, (2-6C) alkanoyl, alkanoyloxy (2-6C) and a group of the formula: -X3-R10 wherein X3 is a direct bond or is selected from O, CO, SO2 and N (R11), wherein R11 is hydrogen or alkyl (1-4C) ), and R10 is halogen-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl ( 1-4C), N-alkylamino (1-4C) -al quil (1-4C), and N, N_-di- [alkyl (1-4C)] amino-alkyl (1-4C), and wherein any heterocyclyl group in a R6 substituent optionally carries 1 or 2 oxo or thioxo substituents; and wherein any CH2 or CH3 group in a substituent R6, other than a CH2 group in a heterocyclic group, optionally carries in each said CH2 or CH3 group one or more halogen substituents or (1-6C) alkyl or a subsitute selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1 -6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, N-alkylcarbamoyl (1-6C), N, N-di [(1-6C) alkyl] carbamoyl, alkanoyl ( 2-6C), alkanoyloxy (2-6.C), alkanoylamino (2-6C), N-alkyl (1-6C) -alkylamino (2-6C), N-alkylsulfamoyl (1-6C), N, N- di [(1-6C) alkylsulfamoyl, (1-6C) alkanesulfonylamino and (1-6C) -alkyl sulfonylamino (1-6C); A is selected from hydrogen, a group of the formula Z- (CR12R13) P- and R14, wherein p is 1, 2, 3, or 4, each R 2 and R 13, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl ( 2-6C), or a group R12 and R13 attached to the same carbon atom form a cycloalkyl ring (3-7C) or cycloalkenyl (3-7C), and wherein any CH2 or CH3 group in any of R12 and R13 optionally each CH2 or CH3 group has one or more (for example 1, 2 or 3) halogen or alkyl (1-6C) substituents or a substituent selected from hydroxy, cyano, alkyl (1-6C), alkoxy (1-) 6C), amino, alkanoyl (2-6C), alkylamino (1-6C) and di- [(1-6C) alkyl] amino, Z is selected from hydrogen, OR15, NR16R17, alkylsulfonyl (1-6C), alkanesulfonylamino ( 1 -6C) and N.-alkyl (1-6C) -alkanesulfonylamino (1-6C), wherein each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1 - 6C), alkenyl (2-6C), alkynyl (2-6C) and alkoxycarbonyl (1-6C), or Z is a group of the formula: Q2-X 4-where X4 is selected from O, N (R1 8), SO2 and SO2N (R18), where R1 8 is hydrogen or alkyl (1-6C), and Q2 is cycloalkyl (3-7C), cycloalkenyl (3-7C) or heterocyclyl, R14 is selected from hydrogen, OR19 and NR16R17, wherein R19 is selected from alkyl (1) -6C), alkenyl (2-6C) and alkynyl (2-6C), and wherein R16 and R17 are as defined above, or R14 is a group of the formula:. Q3-X5-wherein X5 is selected from O and N (R20), wherein R20 is hydrogen or alkyl (1-6C), and Q3 is cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1 -6C), cycloalkenyl (3-7C), cycloalkenyl (3-7C) -alkyl (1 -6C), heyerocyclyl and heterocyclyl-alkyl (1-6C), or R14 is Q4 wherein Q4 is cycloalkyl (3-7C) , (3-7C) cycloalkyl-(1-6C) alkyl, (3-7C) cycloalkenyl, (3-7C) cycloalkenyl (1-6C), heterocyclyl or heterocyclyl-alkyl (1-6C), and wherein Adjacent carbon atoms in any alkylene chain (2-6C) in a substiluyenie Z or R14 are optionally separated by the insertion in the chain of a selected group of O, S, SO, SO2, N (R21), CO, - C = C and -C = C-, wherein R21 is hydrogen or alkyl (1-6C), and wherein any heterocyclyl group in a substituent Z or R14 optionally carries one or more (for example 1, 2 or 3) substitutes , which may be the same or different, selected from halogen, frifluoromethyl, cyano, nifro, hydroxy, amino, formyl, mercapio, quil (1 -6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [alkyl (1-6C)] amino, (2-6C) alkanoyl, (2-6C) alkanoyloxy and a group of the formula: -X6-R22 wherein X6 is a direct bond or is selected from O, CO, SO2 and N (R23), wherein R23 is hydrogen or alkyl (1-4C), and R22 is halo-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C), N-alkylamino (1-4C) -alkyl (1-4C), and N. , N.-di [alkyl (1-4C)] amino-alkyl (1-4C), and wherein any heterocyclyl group in a substiluent Z or R14 optionally carries 1 or 2 substituents oxo or thioxo, and wherein any CH2 group or CH3 in a group Z or R14, different from a group CH2 in a heterocyclyl ring, optionally carries in each said group CH2 or CH3 one or more substituents of halogen or alkyl (1-6C) or a substitute selected from hydroxy, cyano amino, carboxy, carbamo il, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1- 6C), di- [(1-6C) alkyl] amino, N-alkylcarbamoyl (1-6C), N, N-di [(1-6C) alkyl] carbamoyl, (2-6C) alkanoyl, alkanoyloxy (2C). -6C), alkanoylamino (2-6C), JN-alkyl (1-6C) -alkylamino (2-6C), N-alkylsulfamoyl (1-6C), N, N-di [(1-6C) alkyl] sulfamoyl , alkanesulfonylamino (1-6C) and N-alkyl (1-6C) -alkanesulfonylamino (1-6C); or a pharmaceutically acceptable salt thereof. According to a second aspect of the invention there is provided a quinazoline derivative of the formula I wherein: m is 0, 1 or 2; each R1, which may be the same or different, is selected from hydroxy, (1-6C) alkoxy, (3-7C) -oxocycloalkyl, and (3-7C) -alkoxy (1-6C) cycloalkyl, and wherein any CH2 or CH3 group in a substituent R1 optionally carries in each said CH2 or CH3 group one or more halogen sub stances or alkyl (1-6C), or a substituent selected from hydroxy and (1-6C) alkoxy, R2 is hydrogen or alkyl (1-4C); n is 0, 1, 2, 3 or 4; each R3, which may be the same or different, is selected from halogen, (1-4C) alkyl, urea fluoride, (1-4C) alkoxy, (2-4C) alkenyl, and (2-4C) alkynyl; X1 is selected from O, S, SO, SO2, N (R7), CH (OR7), CON (R7), N (R7) CO, SO2N (R7), N (R7) SO2, OC (R7) 2, C (R7) 2O, SC (R7) 2, C (R7) 2S, CO, C (R7) 2N (R7) and N (R7) C (R7) 2, wherein each R7, which may be the same or different, it is hydrogen or alkyl (1-6C); Q1 is aryl, or heteroaryl, and wherein Q optionally carries one or more substifuyeníes (for example 1, 2 or 3), which may be the same or different, selected from halogen, cyano, nitro, hydroxy, amino, carboxy, carbamoyl , sulfamoyl, formyl, mercapto, alkyl (1-6C), alkenyl (2-8C), alkynyl (2-8C), alkoxy (1-6C), alkenyloxy (2-6C), alkynyloxy (2-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, alkoxycarbonyl (1-6C), N-alkylcarbamoyl ( 1-6C), N, N-di- [(1-6C) alkyl] carbamoyl, (2-6C) alkanoyl, (3-6C) alkenoyl, (3-6C) alkynyl, (2-6C) alkanoyloxy, alkanoylamino (2-6C), JN-alkyl (1-6C) -alkylamino (2-6C), alkenoylamino (3-6C), jN-alkyl (1-6C) -alkenoylamino (3-6C), alkynylamino (3-6C) ), JN-alkyl (1-6C) -alkynylamino (3-6C), N-alkylsulfamoyl (1-6C), N, N-di- [alkyl (1-6C)] sulfamoyl, alkanesulfonylamino (1-6C) , N-alkyl (1-6C) -alkanesulfonylamino (1-6C) and a group of the formula: -X2-R8 wherein X2 is an direct lace or is selected from O, CO and N (R9), wherein R9 is hydrogen or alkyl (1-6C), and R8 is halo-alkyl (1-6C), hydroxy-alkyl (1-6C), carboxy -alkyl (1-6C), alkoxy (1-6C) -alkyl (1-6C), cyano-alkyl (1-6C), amino-alkyl (1-6C), .N-alkylamino (1-6C) - (1-6C) alkyl, N.N.-di [(1-6C) alkyl] amino (1-6C) alkyl, (2-6C) alkanoylamino (1-6C) alkyl, N-alkyl (1) -6C) -alkylamino (2-6C) -alkyl (1-6C), alkoxycarbonylamino (1-6C) -alkyl (1-6C), carbamoyl-alkyl (1-6C), N-alkylcarbamoyl (1-6C) - alkyl (1-6C), N, N-di [(1-6C) alkyl] carbamoylalkyl (1-6C), alkylthio (1-6C) -alkyl (1-6C), alkylsulfinyl (1-6C) - alkyl (1-6C), alkylsulfonyl (1-6C) -alkylsulfamoyl (1-6C) alkyl (1-6C), N-alkylsulfamoyl (1-6C) alkyl (1-6C), N, N-di-alkylsulfamoyl ( 1-6C) alkyl (1-6C), alkanoyl (2-6C) -alkyl (1-6C), alkanoyloxy (2-6C) -alkyl (1-6C) or alkoxycarbonyl (1-6C) -alkyl (1- 6C), and wherein any group CH2 or CH3 in -X1-Q1 optionally carries in each said group CH2 or CH3 one or more (e.g. 1, 2, or 3) subslides of halogen or (1-6C) alkyl or a substituted substituye of hydroxy, cyano, amino, (1-4C) alkoxy, alkylamino (1-4C) and di- [alkylamino (1-4C) )]; R4, R4a, R5 and R5a, which may be the same or different, are selected from hydrogen and alkyl (1-6C), or R4 and R4a june with the carbon atom to which they are attached form a cycloalkyl ring (3- 7C), or R5 and R5a together with the carbon atom to which they are attached form a cycloalkyl (3-7C) ring, and wherein any CH2 or CH3 group in any of R4, R4a, R5 and R5a optionally bears in each said CH2 or CH3 group one or more (for example 1, 2 or 3) halogen substituents or a substituent selected from hydroxy, cyano, (1-6C) alkoxy, amino, (2-6C) alkanoyl, (1-6C) alkylamino and di- [alkylamino (1-6C)]; R6 is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C), cycloalkenyl ( 3-7C), cycloalkenyl (3-7C) -alkyl (1-6C), heterocyclyl and heterocyclyl-alkyl (1-6C), and wherein any heterocyclyl group in a substituate R6 optionally carries one or more substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1 -6C), alkylsulfonyl (1 -6C), alkylamino (1 -6C), di- [(1-6C) alkyl] amino, (2-6C) alkanoyl, (2-6C) alkanoyloxy and from one group of the formula: wherein X3 is a direct bond or is selected from O, CO, SO2 and N (R11), wherein R1 is hydrogen or alkyl (1-4C), and R10 is halogen-alkyl (1-4C) , hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C), N-alkylamino (1-4C) -Ilkyl (1-4C), and N, N-di- [(1-4C) alkyl] amino-alkyl (1-4C), and wherein any heterocyclyl group in a substituent R6 optionally carries 1 or 2 oxo substituents or tioxo; and wherein any CH2 or CH3 group in a substituent R6, other than a CH2 group in a heterocyclyl group, optionally carries in each said CH2 or CH3 group one or more halogen substituents or alkyl (1-6C) or a substituent selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1 -6C), alkylamino (1 -6C), di- [alkyl (1 -6C)] amino, N.-alkylcarbamoyl (1 -6C), N., N.-di [alkyl (1-6C)] carbamoyl, alkanoyl (2-6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), N-alkyl (1 -6C) -alkanoylamino (2-6C), N-alkylsulfamoyl (1 -6C), N, N- di [alkyl (1-6C)] sulfamoyl, alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C); A is selected from hydrogen, a group of the formula Z- (CR12R13) P- and R14, wherein p is 1, 2, 3, or 4, each R12 and R13, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl (2-6C), or a group R12 and R13 attached to the same carbon atom form a ring of cycloalkyl (3-7C) or cycloalkenyl (3-) 7C), and wherein any CH2 or CH3 group in any of R12 and R13 optionally carries in each said CH2 or CH group one or more (for example 1, 2 or 3) halogen or alkyl (1-6C) substituents or a substituent selected from hydroxy, cyano, alkyl (1-6C), alkoxy (1-6C), amino, alkanoyl (2-6C), alkylamino (1-6C) and di- [(1-6C) alkyl] amino, Z is selected from hydrogen, OR15, NR16R17, alkylsulfonyl (1-6C), alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonamino (1-6C), wherein each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl (2-6) C), or Z is a group of the formula: Q2-X4-wherein X4 is selected from O, N (R1 8), SO2 and SO2N (R18), wherein R18 is hydrogen or alkyl (1-6C), and Q2 is cycloalkyl (3-7C), cycloalkenyl (3-7C) or heterocyclyl, R14 is selected from hydrogen, OR19 and NR16R17, wherein R19 is selected from alkyl (1-6C), alkenyl (2-6C) and alkynyl (2-6C), and wherein R16 and R17 are as defined above, or R14 is a group of the formula: Q3-X5-wherein X5 is selected from O and N (R20), wherein R20 is hydrogen or alkyl (1-6C), and Q3 is cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C), cycloalkenyl (3-7C), cycloalkenyl (3-7C) -alkyl (1-6C) ), heterocyclyl, heterocyclyl-alkyl (1-6C), or R14 is Q4 wherein Q4 is cycloalkyl (3-7C), cycloalkenyl (3-7C) or heterocyclyl, and wherein adjacent carbon atoms in any alkylene chain ( 2-6C) in a subscript Z or R14 are optionally separated by the insertion in the chain of a selected group of O, S, SO, SO2, N (R21), CO, -C = C and -C = C-, wherein R21 is hydrogen or alkyl (1-6C), and wherein any heterocyclyl group in a substituent Z or R14 optionally carries one or more (for example 1, 2 or 3) substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C) , alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, (2-6C) alkanoyl, alkanoyloxy ( 2-6C) and a group of the formula: -X6-R22 wherein X6 is a direct bond or is selected from O, CO, SO2 and N (R23), wherein R23 is hydrogen or alkyl (1-4C) , and R22 is halogen-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1 -4C), N-alkylamino (1-4C) -alkyl (1-4C), and N, N-di [alky (1-4C)] amino-alkyl (1-4C), and wherein any heterocyclyl group in a subsíiuyenie Z or R14 optionally llele there are 1 or 2 oxo or thioxo subslifuents, and wherein any CH2 or CH3 group in a group Z or R14, other than a CH2 group in a heterocyclyl ring, optionally bears in each said group CH2 or CH3 one or more halogen subsiIugents. or alkyl (1-6C) or a substituent selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1 - 6C), alkylamino (1 -6C), di- [(1-6C) alkyl] amino, JN-alkylcarbamoyl (1 -6C), N, N-di [(1-6C) alkyl] carbamoyl, alkanoyl (2- 6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), l __- alkyl (1 -6C) -alkanoylamido (2-6C), N-alkylsulfamoyl (1 -6C), N, N-di [ alkyl (1 -6C)] sulfamoyl, alkanesulfonylamino (1 -6C) and N.- alkyl (1 -6C) -alkanesulfonylamino (1 -6C); or a pharmaceutically acceptable salt thereof. According to a preferred aspect of the invention there is provided a quinazoline derivative of the formula I wherein: m is 0, 1 or 2; each R1, which may be the same or different, is selected from hydroxy, (1-6C) alkoxy, (3-7C) cycloalkyl- and cycloalkyl (3-7C) -alkoxy (1-6C), and wherein any CH2 or CH3 group in a substituent R1 optionally carries in each said CH2 or CH3 group one or more halogen or alkyl (1 -6C) subsifiuyenis, or a subsyiyenyen selected from hydroxy and (1-6C) alkoxy, R2 is hydrogen or alkyl (1 -4C); n is 0, 1, 2, 3 or 4; each R3, which may be the same or different, is selected from halogen, alkyl (1-4C), trifluoromethyl, alkoxy (1-4C), alkenyl (2-4C) and alkynyl (2-4C); X1 is selected from O, S, SO, SO2, N (R7), CH (OR7), CON (R7), N (R7) CO, SO2N (R7), N (R7) SO2, OC (R7) 2, C (R7) 2O, SC (R7) 2, C (R7) 2S, CO, C (R7) 2N (R7) and N (R7) C (R7) 2, wherein each R7, which may be the same or different, it is hydrogen or alkyl (1-6C); Q1 is aryl, or heteroaryl, and wherein Q1 optionally bears one or more substituents (for example 1, 2 or 3), which may be the same or different, selected from halogen, cyano, nitro, hydroxy, amino, carboxy, carbamoyl , sulfamoyl, formyl, mercapto, (1-6C) alkyl, (2-8C) alkenyl, (2-8C) alkynyl, (1-6C) alkoxy, (2-6C) alkenyloxy, (2-6C) alkynyloxy, alkynyl (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, alkoxycarbonyl (1-6C), JN-alkylcarbamoyl ( 1-6C), N., N.-di- [aikil (1-6C)] carbamoyl, alkanoyl (2-6C), alkenoyl (3-6C), alkyinoyl (3-6C), alkanoyloxy (2-6C) , alkanoylamino (2-6C), JN-alkyl (1-6C) -alkylamino (2-6C), alkenoylamino (3-6C), N-alkyl (1-6C) -alkenoylamino (3-6C), alkynylamino (3) -6C), N-alkyl (1-6C) -alkynylamino (3-6C), N-alkylsulfamoyl (1-6C), N, J_-di- [(1-6C) alkyl] sulfamoyl, alkanesulfonylamino ( 1-6C), JN-alkyl (1-6C) -alkanesulfonylamino (1-6C) and a group of the formula: -X2-R8 wherein X2 is a direct bond or is selected from O, CO and N (R9), wherein R9 is hydrogen or alkyl (1-6C), and R8 is halogen-alkyl (1-6C), hydroxy-alkyl (1-6C), carboxy-alkyl (1-6C), alkoxy (1-6C) -alkyl (1-6C), cyano-alkyl (1-6C), amino-alkyl (1-6C), N-alkylamino (1-6C) - alkyl (1-6C), JN, JN-dí [(1-6C) alkyl] amino (1-6C) alkyl, (2-6C) alkanoylamino (1-6C) alkyl, N-alkyl (1-6C) ) -alkanoylamino (2-6C) -alkyl (1-6C), alkoxycarbonylamino (1-6C) -alkyl (1-6C), carbamoyl-alkyl (1-6C), N-alkylcarbamoyl (1-6C) -alkyl ( 1-6C), N, N-di [(1-6C) alkyl] carbamoyl-(1-6C) alkyl, (1-6C) alkyl- (1-6C) alkyl, (1-6C) alkylsulfinyl-alkyl ( 1-6C), alkylsulfonyl (1-6C) -alkylsulfamoyl (1-6C) alkyl (1-6C), N-alkylsulfamoyl (1-6C) alkyl (1-6C), JN, N-di-alkylsulfamoyl (1- 6C) alkyl (1-6C), alkanoyl (2-6C) -alkyl (1-6C), alkanoyloxy (2-6C) -alkyl (1-6C) or alkoxycarbonyl (1-6C) -alkyl (1-6C) , and wherein any CH2 or CH3 group in -X1-Q1 optionally carries in each said CH2 or CH3 group one om (for example 1, 2, or 3) substituents of halogen or alkyl (1-6C) or a substituent selected from hydroxy, cyano, amino, alkoxy (1-4C), alkylamino (1-4C) and di- [alkylamino] (1 -4C)]; R4, R4a, R5 and R5a, which may be the same or different, are selected from hydrogen and alkyl (1-6C), and wherein any CH2 or CH3 group in any of R4, R4a, R5 and R5a optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) substituted for halogen or a substituent selected from hydroxy, cyano, (1-6C) alkoxy, amino, (2-6C) alkanoyl, alkylamino (1-6C) ) and di- [alkylamino (1 -6C)]; R6 is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C), cycloalkenyl ( 3-7C), cycloalkenyl (3-7C) -alkyl (1-6C), heterocyclyl and heterocyclyl-alkyl (1-6C), and wherein any heterocyclyl group in a R6 substituent optionally carries one or more substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1) -6C), alkylsulfinyl (1 -6C), alkylsulfonyl (1 -6C), alkylamino (1 -6C), di- [alkyl (1 -6C)] amino, alkanoyl (2-6C), alkanoyloxy (2-6C) and from a group of the formula: -X3-R10 wherein X3 is a direct bond or is selected from O, CO, SO2 and N (R11), wherein R11 is hydrogen or alkyl (1-4C), and R10 is halogen-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C), N-alkylamino (1-4C) -alkyl (1-4C), and N., JN-di- [(1-4C) alkyl] amino-alkyl (1-4C), and wherein any heterocyclyl group in a substituent R6 optionally carries 1 or 2 substiuuyeníes oxo or thioxo; and wherein any CH.sub.2 or CH.sub.3 group in a R.sub.6 subsiticide, differentiates a CH.sub.2 group in a heterocyclyl group, optionally bears in each said CH.sub.2 or CH.sub.3 group one or more halogen substituents or (1-6C) alkyl or a substituent selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkyl (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1 -6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, N-alkylcarbamoyl (1-6C), N.N.-di [(1-6C) alkyl] carbamoyl, alkanoyl ( 2-6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), N-alkyl (1-6C) -alkylamino (2-6C), N-alkylsulfamoyl (1-6C), N, N-di [ alkyl (1-6C)] sulfamoyl, alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C); A is selected from hydrogen, a group of the formula Z- (CR12R13) P- and R14, wherein p is 1, 2, 3, or 4, each R12 and R13, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl (2-6C), or a group R12 and R13 attached to the same carbon atom form a ring of cycloalkyl (3-7C) or cycloalkenyl (3-) 7C), and wherein any CH2 or CH3 group in any of R12 and R13 optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) halogen substituents or alkyl (1-6C) or a selected substituent of hydroxy, cyano, alkyl (1-6C), alkoxy (1-6C), amino, alkanoyl (2-6C), alkylamino (1-6C) and di- [(1-6C) alkyl] amino, Z is selected from hydrogen, OR15, NR16R17, alkylsulfonyl (1-6C), alkanesulfonylamino (1-6C) and N-alkyl (1-6C) -alkanesulfonylamino (1-6C), wherein each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C) and alkoxycarbonyl (1-6C), or Z is a group of the formula: Q2-X4-wherein X4 is selected from O, N (R1 8), SO2 and SO2N (R1 8), wherein R18 is hydrogen or alkyl (1-6C), and Q2 is cycloalkyl (3-7C), cycloalkenyl (3-7C) or heterocyclyl, R14 is selected from hydrogen, OR19 and NR16R17, wherein R19 is selected from alkyl (1 - 6C), alkenyl (2-6C) and alkynyl (2-6C), and wherein R16 and R17 are as defined above, or R14 is a group of the formula: Q3-X5-wherein X5 is selected from O and N (R20), wherein R20 is hydrogen or alkyl (1-6C), and Q3 is cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C), cycloalkenyl (3-7C), cycloalkenyl (3-7C) -alkyl (1-6C), heterocyclyl and heterocyclyl-alkyl (1-6C), or R14 is Q4 wherein Q4 is cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1 - 6C), cycloalkenyl (3-7C), cycloalkenyl (3-7C) -alkyl (1-6C), heyerocyclyl or heterocyclyl-alkyl (1-6C), and wherein adjacent carbon atoms in any alkylene chain (2- 6C) in a substituent Z or R14 are optionally separated by the insertion in the chain of a selected group of O, S, SO, SO2, N (R21), CO, -C = C and -C = C-, in wherein R21 is hydrogen or alkyl (1-6C), and wherein any heterocyclyl group in a substituent Z or R14 optionally carries one or more (for example 1, 2 or 3) substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C) , alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C)] amino, alkanoyl (2-6C), alkanoyloxy (2-6C) and a group of the formula: -X6-R22 wherein X6 is a direct bond or is selected from O, CO, SO2 and N (R23), wherein R23 is hydrogen or alkyl (1-4C), and R22 is halogen-alkyl (1 -4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C), N-alkylamino (1-4C) -alkyl (1-4C), and N, N-di [alkyl (1-4C)] amino-alkyl (1-4C), and wherein any heterocyclyl group in a substituent Z or R14 optionally carries 1 or 2 oxo or lyoxo subsylsuitable, and wherein any CH2 or CH3 group in a Z or R14 group, other than a CH2 group in a heterocyclyl ring, optionally carries in each said CH2 or CH3 group one or more halogen or alkyl (1) substituents. -6C) or a sub-ester selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkyl (1-6C), alkylsulfinyl ( 1 -6C), alkylsulfonyl (1 -6C), alkylamino (1 -6C), di- [(C 1-6C)] amino, N-alkylcarbamoyl (1 -6C), N, N-di [alkyl (1 -6C)] carbamoyl, alkanoyl (2-6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), N-alkyl (1 -6C) -alkylamino (2-6C), N-alkylsulfamoyl (1-6C) ), JN, N-di [(1-6C) alkyl] sulfamoyl, alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C); or a pharmaceutically acceptable salt thereof. In this specification the generic term "alkyl" includes the straight-chain or branched chain alkyl groups such as propyl, isopropyl and tert-butyl. However, references to individual alkyl groups such as "propyl" are specific for the straight chain version only and references to individual branched chain alkyl groups such as "isopropyl" are specific to the branched chain version only. An analogous convention applies to other generic terms, for example, alkoxy (1-6C) includes methoxy, ethoxy and isopropoxy, alkylamino (1-6C) includes methylamino, ethylamino and isopropylamino and di- [(1-6C) alkyl] amino includes dimethylamino, diethylamino and N-isopropyl-JN-methylamino. It should be understood that, now that the compounds of the formula I defined above can exist in racemic or optically active forms by virtue of one or more asymmetric carbon atoms, the invention includes in its definition any racemic or optically active form possessing the activity mentioned above. It should further be understood that in the names of the chiral compounds (R, S) denote any racemic or phasemic mixture while (R) and (S) denoted the enaniomers. In the absence of (R, S), (R) or (S) in the name should be understood that the name refers to any racemic or racemic mixture, where a scalar mixture contains R and S enantiomers in any relative proportion and a racemic mixture contains R and R enantiomers. S in the 50:50 ratio. The synthesis of optically active forms can be carried out by standard techniques of organic chemistry well known in the art, for example, by syn- thesis of optically active initial ma- terials or by resolution of a racemic form. Similarly, the above-mentioned activity can be evaluated using standard laboratory techniques related to quenching. Suitable values for the generic radicals referred to above include those set forth below. A suitable value for any of the substituents herein (eg, Q) when it is aryl or for the aryl group in a 'Q' group is, for example, phenyl or naphthyl, preferably phenyl. A suitable value for any of the substituents in the present when it is cycloalkyl (3-7C) or for a cycloalkyl (3-7C) defined in the present, for example a 'Q' group or subsitute R1 is, for example, cyclopropyl , cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or bicyclo [2.2.1] heptyl. A suitable value for any of the substituents herein, when it is cycloalkenyl (3-7C) or for the cycloalkenyl group (3-7C) in a sub-solvent is, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl or cycloheptenyl. A suitable value for any of the substituents herein when it is heteroaryl or for the heteroaryl group in a 'Q' group is, for example, an aromatic 5 or 6 membered monocyclic ring or a 9 or 10 membered bicyclic ring with up to five ring hetero-groups selected from oxygen, nitrogen and sulfur, for example furyl, pyrrolyl, thienyl, oxazolyl, isoxazolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1, 3,5-triazenyl, 1,3-benzodioxolyl, benzofuranyl, indolyl, benzofenyl, bezoxazolyl, benzimidazolyl, benzothiazolyl, indazolyl, benzofurazanyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalinyl, cinolinyl or naphthyridinyl. Paríicular heeroaryl groups include, for example, pyridyl, pyrimidyl, pyrazinyl, thiazolyl, isothiazolyl, oxazolyl, and isoxazolyl (more particularly pyridyl, pyrazinyl, thiazolyl, and isoxazolyl). A suitable value for any of the substituents when it is heterocyclyl or for the heterocyclyl group in a substituent is a bicyclic or monocyclic ring of 3 to 10 members partially saturated (ie, ring systems retaining somewhat, but not the full degree of establishment). ) or non-aromatic saturated (ie, ring systems with the highest degree of saturation) with up to five heteroatoms selected from oxygen, nitrogen and sulfur, which, unless otherwise specified, may be carbon or nitrogen bonded, for example oxiranil, oxetanyl, azetidinyl, dihydrofuranyl, tetrahydrofuranyl, 1,3-dioxolanyl, tetrahydropyranyl, 1,4-dioxanil, oxepanyl, pyrrolinyl, pyrrolidinyl, morpholinyl, 4-thiazinyl, 1,1-odoxotetrahydro-1,4-thiazolin, piperidinyl, homopiperidinyl, piperazinyl, homopiperazinyl, dihydropyridinyl, tetrahydropyridinyl, dihydropyrimidinyl, tetrahydropyrimidinyl, tetrahydrofienyl, feirahydroiopyranyl, decahydroisoquinolin il or decahydroquinolinyl, particularly ε-tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, morpholinyl, 1,4-oxazepanyl, thiamorpholinyl, 1,1-dioxotetrahydro-4HH-1,4-thiazinyl, piperidinyl or piperazinyl, more particularly teryhydrofuran-2-M, tetrahydrofuran-3 -yl, tetrahydropyran-4-yl, tetrahydrothien-3-yl, tetrahydrothiopyran-4-yl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, morpholino, morpholin-2-yl, piperidino, piperidin -4-yl, piperidin-3-yl, piperidin-2-yl or piperazin-1-yl. A nitrogen or sulfur atom in a heterocyclyl group can be oxidized to the corresponding N or S oxide, for example 1, 1-dioxoterahydroiienyl, 1 -oxoylhydro-trothienyl, 1,1-dioxoteirahydropylopyranyl or 1-oxotetrahydroliopyranyl. A suitable value for the group carrying 1 or 2 subsitutes oxo or dioxo is, for example, 2-oxopyrrolidinyl, 2-fioxopyrrolidinyl, 2-oxoimidazolidinyl, 2-thioxoimidazolidinyl, 2-oxopiperidinyl, 2,5-dioxopyrrolidinyl 2,5-dioxoimidazolidinil or 2,6-dioxopiperidinyl. Parietal heyerocyclic groups include, for example, partially saturated or non-aromatic saturated monocyclic 3 to 7 membered heterocyclic rings with 1 nitrogen ring or sulfur heteroatom and optionally 1 to 2 heteroatoms selected from nitrogen, oxygen and sulfur. Examples of such rings include azetidinyl, oxazepanil, pyrrolinyl, pyrrolidinyl, morpholinyl, tetrahydro-1,4-thiazinyl, piperidinyl, homopiperidinyl, piperazinyl, homopiperazinyl, dihydropyridinyl, tetrahydropyridinyl, dihydropyrimidinyl, tetrahydropyrimidinyl, tetrahydrothienyl, tetrahydropylopyranyl or iomorpholinyl. Other particular heteroaryl groups include, for example, partially saturated, saturated or monocyclic 4, 5, 6 or 7-membered heterocyclyl rings containing 1 or 2 hetero-atoms selected from oxygen, nitrogen and sulfur, such as oxelanyl azefidinyl, dihydrofuranyl, feyrahydrofuranyl, 1-3. dioxolanyl tetrahydropyranyl, 1,4-dioxanyl, oxepanyl, pyrrolinyl, pyrrolidinyl morpholinyl, tetrahydro-1,4-thiazinyl, 1,1-dioxo-ar-hydrofo-1,4-diazinyl piperidinyl, homopiperidinyl, piperazinyl, homopiperazinyl dihydropyridinyl, tetrahydropyridinyl, dihydropyrimidinyl tetrahydropyrimidinyl, terahydrotenil or tetrahydrothiopyranyl. Additional particular heterocyclic groups include, for example partially saturated 4 to 5 or 7 membered monocyclic heterocyclyl rings containing 1 niorogen atom and optionally 1 heteroatom selected from niologen, oxygen and sulfur such as piperazinyl, pyrrolidinyl, piperidinyl, particularly pyrrolidinyl. -1-yl, pyrrolidin-2-yl, piperazin-1-yl, piperidino or morpholino. Other heterocyclyl groups include, for example, partially saturated or saturated non-aromatic monocyclic, 4-, 5-, 6- or 7-membered heterocyclic rings containing 1 or 2 oxygen atoms such as telrahydrofuranyl, 1,3-dioxolanyl and fetrahydropyranyl (eg feirahydrofuran-2). -il and tefrahydropyran-4-yl). A suitable value for a substituent in the present when it is heterocyclyl-alkyl (1-6C) is, for example, heterocyclylmethyl, 2-heterocyclylethyl and 3-heterocyclylpropyl. The invention comprises corresponding suitable values for other substituents when, for example, preferably a heterocyclyl-alkyl (1-6C), a (3-7C) cycloalkyl (1-6C) alkyl or (3-7C) cycloalkenyl-alkyl ( 1 -6C) is present. Suitable values for any of the substituents in the present, for example the 'R' groups (R1 to R23) or for several groups in a Q \ X1 or A group include: for halogen: fluoro, chloro, bromo and iodo; for alkyl (1-6C): methyl, ethyl, propyl, isopropyl and tert-butyl; for alkenyl (2-8C): vinyl, isopropenyl, allyl and but-2-enyl; for (2-8C) alkynyl: ethynyl, 2-propynyl and but-2-ynyl; for (1-6C) alkoxy: methoxy, ethoxy, propoxy, isopropoxy and butoxy; for alkenyloxy (2-6C): vinyloxy and allyloxy; for (2-6C) alkynyloxy: ethynyloxy and 2-propynyloxy; for alkylthio (1-6C): methylthio, eylilium and propylthio; for alkylsulfinyl (1-6C): methylsulfinyl and ethylsulfinyl; for alkylsulfonyl (1-6C): methylsulfonyl and eylsulfonyl; for alkylamino (1-6C): methylamino, ethylamino, propylamino, isopropylamino and butylamino; for di- [alkyl (1 -6C)] amino: dimethylamino, diethylamino, N-ethyl-N-methylamino and diisopropylamino; for alkoxycarbonyl (1-6C): methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl and tert-buzoxycarbonyl; for JN-alkylcarbamoyl (1-6C): JN-methylcarbamoyl, JN-ethylcarbamoyl and JN-propylcarbamoyl; for JN, JN-di- [alkyl (1-6C)] carbamoyl: J _., J __-dimethylcarbamoyl, JN-eyl-J_J.-mefylcarbamoyl and J __, J __-diefilcarbamoyl; for alkanoyl (2-6C): acetyl, propionyl, butyryl and isobutyryl; for alkenyl (3-6C): acryloyl and but-2-enolyl; for alkynyl (3-6C): prop-2-ynyl; for alkanoyloxy (2-6C): acetoxy and propionyloxy; for alkanoylamino (2-6C): aceiamide and propionamido; for JN-alkyl (1 -6C) -alkylamino (2-6C): JN-mefilaceiamido and JN-methylpropionamido; for N-alkylsulfamoyl (1 -6C): JN-meilylsulfamoyl and JN-eylsulfamoyl; for JN, JN-di- [alkyl (1 -6C)] sulfamoyl: N., JN-dimethylsulfamoyl; for alkanesulfonylamino (1-6C): methanesulfonylamino and ethanesulfonylamino; for JN-alkyl (1-6C) -alkanesulfonylamino (1-6C): JN-mephenymethanesulfonylamino and JN-methylenesulfonylamino; for alkenoylamino (3-6C): acrylamido, methacrylamido and crotonamido; for NL- (1-6C) alkyl-alkenoylamino (3-6C): JN-methylacrylamido and JN-methylcrotonamido; for alkynylamino (3-6C): propiolamido; for JN-alkyl (1-6C) -alkynylamino (3-6C): N-methylpropiolamido; for amino-alkyl (1-6C): aminomethyl, 2-aminoethyl, 1-aminoethyl and 3-aminopropyl; for J_-alkylamino (1-6C) -alkyl (1-6C): meilylaminometyl, ethylaminomethyl, 1-methylamino-eyl, 2-methylaminoethyl, 2-erylamino-yl and 3-mephilaminopropyl; for J __, JN-di [(1-6C) alkyl-amino-alkyl (1 -6C): dimethylaminomethyl, diethylaminomethyl, 1-dimethylaminoethyl, 2-dimethylamino-eyl and 3-dimethylaminopropyl; for halogen-alkyl (1-6C): chloromethyl, 2-chloroethyl, 1-chloro-phenyl and 3-chloropropyl; for hydroxy-alkyl (1-6C): hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl and 3-hydroxypropyl; for (1-6C) alkoxy-(1-6C) alkyl: methoxymethyl, eioxymethyl, 1-methoxyethyl, 2-methoxy-ethyl, 2-ethoxyethyl and 3-methoxypropyl; for carboxy-alkyl (1 -6C): carboxymethyl and 2-carboxymethyl; for cyano-alkyl (1 -6C): cyano meryl, 2-cyanoethyl, 1-cyanoethyl and 3-cyanopropyl; for alkyl (1-6C) -alkyl (1-6C): methylthiomethyl, ethylthiomethyl, 2-methylthioethyl, 1-methylthioethyl and 3-methylthiopropyl; for alkylsulfinyl (1-6C) -alkyl (1-6C): methylsulfinylmethyl, ethylsulfinylmethyl, 2-methylsulfinylethyl, 1-methylsulfinylethyl and 3-methylsulfinylpropyl; for alkylsulfonyl (1 -6C) -alkyl (1-6C): methylsulfonylmethyl, ethylsulfonylmethyl, 2-methylsulfonyl-ethyl, 1-methyl-sulfonylethyl and 3-methylsulfonyl-propyl; for alkanoylamino (2-6C) -alkyl (1-6C): acetamidomefil, propionamidometyl and 2-acefamidoethyl; for JN-alkyl (1-6C) -alkylamino (2-6C) -alkyl (1-6C): JN-methylacetamidomethyl, 2- (JN-methylacetamido) eile and 2- (JN-mephylpropionamido) efil; for alkoxycarbonylamino (1-6C) -alkyl (1-6C): methoxycarbonylaminomethyl, ethoxycarbonylaminomethyl, tert-butoxycarbonylaminomethyl and 2-methoxycarbonylaminoethyl; for alkanoyl (2-6C) -alkyl (1-6C): acetylmethyl and 2-acetylelyl; alkanoyloxy (2-6C) -alkyl (1-6C): acetoxymethyl, 2-acetoxyethyl and 2-propionyloxyethyl; for carbamoyl-alkyl (1-6C): carbamoylmethyl, 1-carbamoylethyl, 2-carbamoylethyl and 3-carbamoylpropyl; for JN-alkylcarbamoyl (1 -6C) -alkyl (1-6C): JN-methylcarbamoylmethyl, JN-ethylcarbamoylmethyl, JN-propylcarbamoylmethyl, 1- (JN-methylcarbamoyl) efil, 1- (JN-ethylcarbamoyl) eyl, 2- ( N -methylcarbamoyl) ethyl, 2- (N-ethylcarbamoyl) ethyl and 3- (N-methylcarbamoM) propyl; for JN, N.-dí [alkyl (1-6C)] carbamoyl-alkyl (1-6C): JN, JN-methylcarbamoylmethyl, JN. J. diefilcarbamoylmethyl, 2- (JN, JN-dimethylcarbamoyl) ethyl, and 3- (JN, JN-dimethylcarbamoyl) propyl; for sulfamoyl (1-6C) alkyl: sulfamoylmethyl, 1-sulfamoyleryl, 2-sulfamoylefil and 3-sulfamoylpropyl; for JN-alkyl sulfamoM (1-6C) -alkyl (1-6C): JN-methylsulfamoylmethyl, JN-ethylsulfamoylmethyl, JN-propylsulfamoylmethyl, 1- (JN-methylsulfamoyl) ethyl, 2- (JN-methylsulfamoyl) ethyl and 3- ( JN-mephilsulfamoyl) propyl; and for JN, JN di-alkylsulfamoyl (1 -6C) alkyl (1-6C): N, N-dimethylsulfamoylmethyl, N, N-diethylsulfamoylmethyl, JN methyl, JN-eylsulfamoylmethyl, 1 - (JN, JN-dimethylsulfamoyl) ethyl, 1 - (, -diethylsulfamoyl) ethyl, 2- (J_J., I _.- dimethylsulfamoyl) ethyl, 2- (JN, N-diethylsulfamoyl) ethyl and 3- (JN, JN-dimethylsulfamoyl) propiI. When reference is made to the group alkyl (1-4C) in this specification, it is to be understood that such groups refer to alkyl groups confining up to 4 carbon atoms. A skilled person will note that representative examples of such groups are those listed above under alkyl (1-6C) which contain up to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl and tert-butyl. Similarly, reference to alkyl group (1 -3C) refers to alkyl groups containing up to 3 carbon atoms such as methyl, ethyl, propyl and isopropyl. A similar convention is adopted for the other groups listed above such as (1-4C) alkoxy, (2-4C) alkenyl, (2-4C) alkynyl and (2-4C) alkanoyl. When, as defined herein above, in the group of the formula -X1-Q1 and X1 is, for example, a linker group OC (R7) 2, it is the oxygen atom, not the carbon atom, of the group OC (R7) 2 linker that binds to the phenyl ring in formula I and the carbon atom binds to group Q1. Similarly when X1 is a linking group N (R7) C (R7) 2 the nitrogen atom of the linking group N (R7) C (R7) 2 is attached to the phenyl ring in the formula I and the carbon atom is attached to group Q1. A similar convention applies to other linking groups used herein, for example, when A is a group of the formula Z- (CR12R13) P- and Z is Q2-X4- and X4 is SO2N (R1 8), the group SO2 binds to Q2 and the nitrogen atom binds to X4 in formula I. It is to be understood that references herein to adjacent carbon atoms in any (2-6C) alkylene chain in a group can optionally be separated by the insertion in the chain of a group such as O or C = c refers to the insertion. , of the specified group between two carbon atoms in an alkylene chain. For example, when A is R 14 and R 14 is a 2-pyrrolidin-1-ylethoxy group the insertion of a C = C group into the ethylene chain gives rise to a 4-pyrrolidin-1-ylbut-2-ynyloxy group. When a CH2 or CH3 group is referred to herein optionally carrying in each said CH2 or CH3 group one or more halogen substiluyeníes or alkyl (1-6C), there are suitably 1 or 2 substituents of halogen or alkyl (1) -6C) present in each said CH2 group and there are suitably 1, 2 or 3 of such substihuyenis present in each said CH3 group. Where any CH2 or CH3 group is referred to herein optionally carrying in each said CH2 or CH3 group a substitution as defined herein, suitable subsitutes thus formed include, for example, heterocyclyl groups substituted by hydroxy-alkoxy (1-) 6C) lales such as 2-hydroxy-3-piperidinopropoxy and 2-hydroxy-3-morpholinopropylamino, hydroxy-heyerocyclyl subsfifuido-alkylamino (1-6C) groups such as 2-hydroxy-3-piperidinopropylamino and 2-hydroxy-3-morpholinopropylamino and substiuuted hydroxy-alkanoyl (2-6) groups such as hydroxyacetyl, 2-hydroxypropionyl and 2-hydroxybutyryl. Where reference is made in the present to, for example, R4 and R4a together with the carbon atom to which they are attached to form a (3-7C) cycloalkyl ring herein, the ring thus formed is a cycloalkylidene (3-7C) group, for example a cyclopropyldene group of the formula: X " where * represents the links of the cyclopropylidene group. It should be understood that the quinazoline in the formula I is unsubstituted in the 2-position in the quinazoline ring. It should be understood that certain compounds of the formula I can exist in solvated as well as unsolvated forms such as, for example, hydrated forms. It is to be understood that the invention comprises all solvated forms that show an inhibitory effect on a tyrosine kinase of the erbB receptor. It should be understood that certain compounds of the formula I may show polymorphism, and that the invention comprises all such forms that show an inhibitory effect on an erbB receptor tyrosine kinase.

It should also be understood that the invention relates to all tauimeric forms of the compounds of the forms of the formula I which show an inhibitory effect on an erbB receptor tyrosine kinase. A pharmaceutically acceptable salt of a compound of the formula I is, for example, an acid addition salt of a compound of the formula I, for example, an acid addition salt with an inorganic or organic acid such as hydrochloric, hydrobromic acid, sulfuric, trifluoroacetic, citric or maleic; or, for example, a salt of a compound of the formula I which is suitably acid, for example, an alkaline or alkali earth metal salt such as a calcium or magnesium salt, or an ammonium salt, or a salt with an organic base such as methylamine, dimethylamine, trimethylamine, piperidine, morpholine or tris- (2-hydroxyethyl) amine. The new particular compounds of the invention include, for example, quinazoline derivatives of the formula I or pharmaceutically acceptable salts thereof, wherein, unless stated otherwise, each of R1, R2, R3, R4, R4a, R5, R5a, X1, Q1, m, n and A have any of the meanings defined in the present previously or in paragraphs (a) to (yy and yyy) hereunder: (a) m is 0 or 1 and R1, when present, is located at position 7 on the quinazoline ring in formula I; (b) R1 is selected from hydroxy, (1-6C) alkoxy, hydroxy (1-6C) alkoxy, (1-6C) alkoxy- (1-6C) alkoxy, (3-7C) cycloalkyl- and cycloalkyl (3C) alkoxy -7C) - (1-6C) alkoxy, and wherein any CH2 or CH3 group in a substituent R1 optionally carries in each said CH2 or CH3 group one or more substituents selected from fluoro and chloro; (c) m is 0 or 1 and R1, when present, is located at position 7 on the quinazoline ring and is selected from (1-6C) alkoxy, cyclopropyl-alkoxy (1-4C), cyclobutyl-alkoxy ( 1 -4C), cyclopentyl-alkoxy (1-4C) and cyclohexyl-alkoxy (1-6C), and wherein any CH2 or CH3 group in a substituent R1 optionally carries in each said group CH2 or CH3 one or more fluoro substituents or chlorine, or a substituent selected from hydroxy, methoxy and eloxi; (d) m is 1 and R1 is located at position 7 on the quinazoline ring and is (1-4C) alkoxy, for example meioxy or ethoxy, and wherein any CH2 or CH3 group on a substituent R1 optionally carries on each said CH2 or CH3 group one or more fluoro or chloro substituents, or a substituent selected from hydroxy, methoxy and ethoxy; (e) m is 1 and R1 is located at position 7 on the quinazoline ring and is selected from methoxy, ethoxy, propyloxy, isopropyloxy, cyclopropylmethoxy, 2-hydroxyethoxy, 2-fluoroethoxy, 2-methoxyethoxy, 2-ethoxyethoxy, trifluoromeloxi , 2,2-difluoroethoxy and 2,2,2-trifluoroethoxy; (f) m is 1 and R1 is located at position 7 on the quinazoline ring and is methoxy; (g) m is 0; (h) R2 is hydrogen or methyl; (i) R2 is hydrogen; (j) n is 0, 1 or 2 and, when n is present, at least one R3 is in the meta position (position 3) relative to the nitrogen of the anilino group in the formula I; (k) n is 0, 1 or 2 and, when present, at least one R3 is in a meta position (position 3) relative to the nitrogen of the anilino group in the formula I, and wherein R3 is selected from halogen, alkyl (1-6C), alkoxy (1-4C) and alkynyl (2-4C); (I) n is 0, 1 or 2 and, when present, at least one R3 is at a meia position (position 3) relative to the nitrogen of the anilino group in the formula I, and wherein R3 is selected from halogen and alkyl (1 -4C); (m) n is 0 or 1 and, when present, R3 is in a meta position (position 3) relative to the nilrogen of the anilino group in formula I, and wherein R3 is selected from halogen (particularly fluoro or chloro) and alkyl (1-4C); (n) n is 0 or 1 and, when present, R3 is in a meta position (position 3) relative to the nihinogen of the anilino group in formula I and wherein R3 is selected from cyano, fluoro, chloro, methyl, methoxy and ethynyl (particularly fluoro, chloro, methyl, methoxy and ethynyl); (o) n is 1 and R3 is in a meta position (position 3) relative to the nitrogen of the anilino group in the formula I, and wherein R3 is selected from halogen (particularly fluoro or chloro) and alkyl (1-4C); (p) n is 1 and R3 is in a mefa position (position 3) relative to the nitrogen of the anilino group in the formula I and wherein R3 is selected from cyano, fluoro, chloro, methyl, methoxy and ethynyl (particularly fluoro, chloro, methyl, methoxy and ethynyl); (q) n is 1 and R3 is in a meta position (position 3) relative to the nitrogen of the anilino group in the formula I and wherein R3 is selected from chloro and methyl; (r) n is 1, R3 is chlorine and where R3 is in a meta position (position 3) relating to the nitrogen of the anilino group in the formula I; (s) n is 1, R3 is methyl and where R3 is in a meta position (position 3) relative to the nitrogen of the anilino group in the formula I; (t) X1 is selected from O, S, OC (R7) 2, SC (R7) 2, SO, SO2, N (R7), CO, and N (R7) C (R7) 2, wherein each R7, which may be the same or different, is selected from hydrogen or alkyl (1-6C); (u) X1 is selected from O, S and OC (R7) 2 wherein each R7 is, independently, hydrogen or alkyl (1-4C); (v) X1 is selected from S and OC (R7) 2 wherein each R7 is, independently, hydrogen or alkyl (1-4C); (w) X1 is selected from O and OC (R7) 2 wherein each R7 is, independently, hydrogen or alkyl (1-4C) (particularly hydrogen or alkyl (1-2C)); (x) X1 is selected from O, S, OCH2 and OC (CH3) 2; (y) X1 is selected from O, OCH2 and OC (CH3) 2; (z) X1 is selected from O, S and OCH2; (aa) X1 is O; (bb) X1 is S; (ce) X1 is OCH2; (dd) X1 is OC (CH3) 2; (ee) X1 is selected from O, OCH2 and OC (CH3) 2, n is 0 or 1 and, when present, R3 is selected from halogen (particularly chloro) and alkyl (1-4C) (particularly methyl); (ff) X1 is OCH2 l n is 0 or 1 and, when present, R3 is halogen, parficularly chloro; (gg) X1 is OCH2, n is 1, R3 is selected from fluoro, chloro and methyla (particularly chloro and meily), and wherein R3 is in a meta position (position 3) relative to the nihinogen of the anilino group in the formula I; (hh) X1 is O, n is 1, R3 is selected from fluoro, chloro and meiil (particularly chlorine and methyl), and wherein R3 is in a meta position (position 3) relative to the nitrogen of the anilino group in the formula I; (ii) X1 is O, n is 1, R3 is methyl, and wherein R3 is in a meta position (position 3) relative to the nihinogen of the anilino group in the formula I; (jj) X1 is OC (CH3) 2, n is 1, R3 is selected from fluoro, chloro and methyl (particularly chloro and methyl), and wherein R3 is in a meta position (position 3) relative to the nitrogen of the anilino group in the formula i; (kk) X1 is OC (CH3) 2, n is 1, R3 is chloro, and wherein R3 is in a meta position (position 3) relative to the nilrogen of the anilino group in the formula I; (II) Q1 is selected from phenyl and a 5- or 6-membered monocyclic heteroaryl ring, such ring contains 1, 2 or 3 heteroatoms independently selected from oxygen, nitrogen and sulfur, and wherein Q1 optionally bears one or more substituents (per Example 1, 2 or 3), which may be the same or different, selected from halogen, cyano, nitro, hydroxy, amino, carboxy, carbamoyl, sulfamoyl, formyl, mercapto, alkyl (1-6C), alkenyl (2-8C) ), alkynyl (2-8C), alkoxy (1-6C), alkenyloxy (2-6C), alkynyloxy (2-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C) , alkylamino (1-6C), di- [(1-6C) alkyl] amino, alkoxycarbonyl (1-6C), JN-alkylcarbamoyl (1-6C), JN, N-di- [alkyl (1-6C)] carbamoyl, alkanoyl (2-6C), alkenoyl (3-6C), alkynylo (3-6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), JN-alkyl (1-6C) -alkanoylamino (2- 6C), alkenoylamino (3-6C), JN-alkyl (1-6C) -alkenoylamino (3-6C), alkynylamino (3-6C), JN-alkyl (1-6C) -alkynylamino (3-6C), JN -alquilsulf amyl (1-6C), JN, JN-di- [alkyl (1-6C)] sulfamoyl, alkanesulfonylamino (1-6C), JN-alkyl (1-6C) -alkanesulfonylamino (1-6C) and a group of the formula: -X2-R8 wherein X2 is a direct bond or is selected from O, CO and N (R9), wherein R9 is hydrogen or alkyl (1-6C), and R8 is halo-alkyl (1-6C) , hydroxy-alkyl (1-6C), carboxy-alkyl (1-6C), alkoxy (1-6C) -alkyl (1-6C), cyano-alkyl (1-6C), amino-alkyl (1-6C), JN-alkylamino (1-6C) -alkyl (1-6C), JN, JN-di [(1-6C) alkyl] amino- alkyl (1-6C), alkanoylamino (2-6C) -alkyl (1-6C), N-alkyl (1-6C) -alkylamino (2-6C) -alkyl (1-6C), alkoxycarbonylamino (1-6C) -alkyl (1-6C), carbamoyl-alkyl (1-6C), N-alkylcarbamoyl (1-6C) -alkyl (1-6C), J __., JN-di [(1-6C) alkyl] carbamoyl-alkyl (1-6C), alkylthio (1-6C) -alkyl (1-6C), alkylsulfinyl (1-6C) -alkyl (1-6C), alkylsulfonyl (1-6C) -alkylsulfamoyl (1-6C) alkyl (1 -6C), N-alkylsulfamoyl (1-6C) alkyl (1-6C), N-JN-di-alkylsulfamoyl (1-6C) alkyl (1-6C), alkanoyl (2-6C) -alkyl (1-6C) ), (2-6C) alkanoyloxy (1-6C) alkyl or (1-6C) alkoxycarbonyl (1-6C) alkyl, and wherein any CH2 or CH3 group in -X1-Q1 optionally carries in each said CH2 group or CH3 one or more (for example 1, 2, or 3) substituents of halogen or (1-6C) alkyl or a substituent selected from hydroxy, cyano, amino, (1-4C) alkoxy, alkylamino (1-4C) and di- [alkylamino (1-4C)]; (mm) Q1 is selected from phenyl and a 5- or 6-membered monocyclic heteroaryl ring, such ring contains 1 nitrogen heteroatom and optionally 1 additional heteroatom selected from oxygen, nitrogen and sulfur, and wherein Q1 optionally bears one or more substituents ( for example 1, 2 or 3), which may be the same or different, as defined herein above in (II), (nn) Q1 is phenyl, and wherein Q1 optionally bears one or more substitutes (for example 1 , 2 or 3), which may be the same or different, as defined herein before in (II); (oo) Q1 is a 5- or 6-membered monocyclic heteroaryl ring, such ring confers 1 nitrogen heteroatom and optionally 1 additional heteroatom selected from oxygen, nitrogen and sulfur, and wherein Q1 optionally bears one or more subsites (eg 1, 2 or 3), which may be the same or different, as defined in the preceding paragraph in (II); (pp) Q1 is selected from phenyl, pyridyl, pyrazinyl, 1,3-thiazolyl, 1H-imidazolyl, 1H-pyrazolyl, 1,3-oxazolyl and isoxazolyl, and wherein Q1 optionally bears one or more substituents (e.g. 1, 2 or 3), which may be the same or different, as defined herein above in (II); (qq) Q1 is selected from phenyl, pyridyl, pyrazinyl, 1,3-thiazolyl and isoxazolyl, and wherein Q1 optionally bears one or more substituents (eg 1, 2 or 3), which may be the same or different, as is defined herein before in (II); (rr) Q1 is selected from pyridyl, pyrazinyl, 1,3-thiazolyl and isoxazolyl, and wherein Q1 optionally bears one or more substituents (eg 1, 2 or 3), which may be the same or different, as defined in the present previously in (II); (ss) Q1 is selected from phenyl, 2-, 3- or 4-pyridyl, 2-pyrazinyl, 1,3-thiazoI-2-yl, 1,3-thiazol-4-yl, 1,3-thiazole-5 -yl, 3-isoxazolyl, 4-isoxazolyl and 5-isoxazolyl, and wherein Q1 optionally bears one or more substituents (for example 1, 2 or 3), which may be the same or different, as defined herein above in (II); (tt) Q1 is selected from 2-, 3-or 4-pyridyl, 2-pyrazinyl, 1,3-thiazol-2-yl, 1,3-yiazol-4-yl, 1,3-thiazol-5-yl , 3-isoxazolyl, 4-isoxazolyl and 5-isoxazolyl, and wherein Q1 optionally bears one or more substituents (eg 1, 2 or 3), which may be the same or different, as defined herein above in ( II); (uu) Q1 is selected from phenyl, 2-pyridyl, 3-pyridyl, 2-pyrazinyl, 1,3-thiazol-2-yl, 1,3-thiazol-4-yl and 3-isoxazolyl, and wherein Q1 optionally carries one or more substituents (eg 1, 2 or 3), which may be the same or different, as defined herein above in (II); (vv) Q1 is selected from 2-pyridyl, 3-pyridyl, 2-pyrazinyl, 1,3-yiazol-2-yl, 1,3-thiazol-4-yl and 3-isoxazolyl, and wherein Q1 optionally bears one or more substituents (for example 1, 2 or 3), which may be the same or different, as defined herein above in (II); (ww) Q1 is selected from 2-pyridyl, 2-pyrazinyl, 1,3-thiazol-4-yl, 1,3-thiazol-5-yl and 3-isoxazolyl, and wherein Q1 optionally bears one or more substituents ( for example 1, 2 or 3), which may be the same or different, as defined herein above in (II); (xx) Q1 is pyrazinyl (particularly 2-pyrazinyl), which optionally bears one or more substituents (eg 1, 2 or 3), which may be the same or different, as defined herein above in (ii); (yy) Q1 is isoxazolyl (particularly isoxazol-3-yl), which optionally bears one or more substitutents (for example 1, 2 or 3), which may be the same or different, as defined herein above in (II) ); (zz) Q1 is pyridyl (particularly 2-pyridyl or 3-pyridyl, more particularly 2-pyridyl), which optionally bears one or more substituents (eg 1, 2 or 3), which may be the same or different, as defined hereinbefore in (II); (aaa) Q1 is 1, 3-thiazolyl (particularly 1, 3-yiazol-4-yl or 1,3-thiazol-2-yl), which optionally carries one or more subsites (eg 1, 2 or 3), which may be the same or different, as defined herein above in (II); (bbb) Q1 is selected from phenyl, pyridyl, pyrazinyl, thiazolyl and isoxazolyl, and wherein Q1 optionally bears one or more substituents (eg 1, 2 or 3), which may be the same or different, selected from halogen , hydroxy, cyano, carboxy, nitro, amino, alkyl (1-4C), alkoxy (1-4C), alkenyl (2-4C), alkynyl (2-4C), alkylthio (1-4C), alkylsulfinyl (1 - 4C), alkylsulfonyl (1-4C), alkanoyl (2-4C), JN-alkylamino (1-4C), N, JN-di [(1-4C) alkyl] amino, alkoxycarbonyl (1-4C), carbamoyl! , JN-alkylcarbamoyl (1-4C), JN, JN-di- [alkyl (1-4C)] carbamoyl, alkanoyloxy (2-4C), alkanoylamino (2-4C), JN-alkyl (1-4C) -alkylamino (2-4C), halogen-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), carboxy-alkyl (1-4C), amino-alkyl (1-4C), JN-alkylamino (1-4C) -alkyl (1-4C) and JN, JN-di- [alkyl (1-4C)] amino-alkyI (1 -4C); (ccc) Q1 is selected from phenyl and a 5- or 6-membered monocyclic heteroaryl ring, such ring contains 1 heteroaryrole of nihologen and optionally 1 additional heteroalomene selected from oxygen, nitrogen and sulfur, and wherein Q1 optionally carries one or more substituents ( for example 1, 2 or 3), which may be the same or different, as defined herein above in (bbb), (ddd) Q1 is phenyl, and wherein Q1 optionally bears one or more substituents (eg 1 , 2 or 3), which may be the same or different, as defined herein above in (bbb); (eee) Q1 is selected from pyridyl, pyrazinyl, 1,3-thiazolyl and isoxazolyl, and wherein Q1 optionally bears one or more substituents (eg, 1, 2 or 3), which may be the same or different, as defined hereinbefore in (bbb); (fff) Q1 is selected from phenyl, 2-, 3- or 4-pyridyl, 2-pyrazinyl, 1,3-thiazol-2-yl, 1,3-thiazol-4-yl, 1,3-thiazole-5 -yl, 3-isoxazolyl, 4 -soxazolyl and 5-isoxazolyl, and wherein Q 1 optionally bears one or more substitutents (for example 1, 2 or 3), which may be the same or different, as defined herein previously in (bbb); (ggg) Q1 is selected phenyl, 2-pyridyl, 3-pyridyl, 2-pyrazinyl, 1,3-thiazol-2-yl, 1,3-yiazol-4-yl and 3-isoxazolyl, and wherein Q1 optionally bears one or more substituents (for example 1, 2 or 3), which may be the same or different, as defined herein above in (bbb); (hhh) Q1 is selected from 2-pyridyl, 3-pyridyl, 2-pyrazinyl, 1,3-thiazol-2-yl, 1,3-thiazol-4-yl and 3-isoxazolyl, and wherein Q1 optionally bears one or more subsíiuyeníes (for example 1, 2 or 3), which can be the same or different, as defined in the previous presentation in (bbb); (iii) Q1 is pyrazinyl (particularly 2-pyrazinyl), which optionally bears one or more substituents (for example 1, 2 or 3), which may be the same or different, as defined herein above in (bbb); (jjj) Q1 is isoxazolyl (particularly isoxazol-3-yl), which optionally bears one or more substituents (for example 1, 2 or 3), which may be the same or different, as defined herein above in (bbb) ); (kkk) Q1 is pyridyl (particularly 2-pyridyl or 3-pyridyl, more particularly 2-pyridyl), which optionally bears one or more substituents (eg 1, 2 or 3), which may be the same or different, as defined hereinbefore in (bbb); (III) Q1 is 1,3-thiazolyl (particularly 1,3-thiazol-4-yl or 1,3-thiazolyl-2-yl), which optionally carries one or more substituents (for example 1, 2 or 3), which may be the same or different, as defined herein above in (bbb); (mmm) Q1 is selected from phenyl, pyridyl, pyrazinyl, thiazolyl and isoxazolyl. and wherein Q1 optionally bears one or more substituents (for example 1, 2 or 3), which may be the same or different, selected from fluoro, chloro, bromo, hydroxy, carboxy, cyano, nitro, amino, methyl, ethyl, isopropyl, methoxy, ethoxy, vinyl, allyl, ethynyl, 2-propynyl, methylthio, methylsulfinyl, methylsulfonyl, acetyl, propionyl, mephilamino, erylamino, N, N-dimethylamino, N, N-dielylamino, methoxycarbonyl of N-methyl-N- Erylamino, Eioxycarbonyl, Carbamoyl, N -methylcarbamoyl, N, N-dimethylcarbamoyl, acetoxy, aceiamide, fluoromethyl, 2-fluoroethyl, chloromethyl, 2-chloroethyl, hydroxymethyl, 2-hydroxyethyl, methoxymethyl, 2-methoxy-yl, cyanomethyl, 2-cyano-phenyl, carboxymethyl, 2-carboxymethyl, aminomethyl, methylaminomethyl, ethylaminomethyl, N, N-dimethylaminomethyl, N, N-diethylaminomethyl, N-methyl-N-ethylaminomethyl, 2-aminoethyl, 2- (methylamino) ethyl, 2- (ephilamino) eyl, 2- (N, N-dimethylamino) ethyl, 2- (N, N-dimethylamino) ethyl, 2- (N-methyl-N-ethylamino) ethyl, carbamoylmethyl, N -methylcarbamoylmethyl and N, Nd im e ti Icarbam oil methyl; (nnn) Q1 is selected from phenyl, 2-pyridyl, 3-pyridyl, 2-pyrazinyl, 1,3-fiazol-2-yl, 1,3-thiazol-4-yl and isoxazol-3-yl, and wherein Q1 optionally bears 1, 2, or 3 substituents, which may be the same or different, as defined herein above in (mmm); (ooo) Q1 is selected from phenyl, 2-pyridyl, 2-pyrazinyl, 1,3-thiazol-4-yl, 1,3-thiazol-5-yl and isoxazole-3-yl, and wherein Q 1 optionally bears 1, 2, or 3 substifuyends, which may be the same or different, as defined herein above in (mmm); (ppp) Q1 is selected from phenyl, 2-pyridyl, 3-pyridyl, 2-pyrazinyl, 1,3-thiazol-2-yl, 1,3-thiazol-4-yl and isoxazol-3-yl, and wherein Q2 optionally bears 1, 2, or 3 substituents, which may be the same or different, selected from halogen (for example fluoro or chloro), hydroxy, alkyl (1-4C) and alkoxy (1-4C); (qqq) Q1 is selected from phenyl, 2-pyridyl, 2-pyrazinyl, 1,3-thiazol-4-yl, 1,3-thiazol-5-yle isoxazol-3-yl, and wherein Q2 optionally bears 1, 2, or 3 substiuyenyes, which may be the same or different, selected from halogen (for example fluoro or chloro), hydroxy , alkyl (1-4C) and alkoxy (1-4C); (rrr) Q1 is selected from phenyl, 2-pyridyl, 3-pyridyl, 2-pyrazinyl, 1,3-thiazol-2-yl, 1,3-thiazol-4-yl and isoxazol-3-yl (particularly phenyl, 2-pyridyl, 3-pyridyl and isoxazol-3-yl), and wherein Q 2 optionally bears 1, 2, or 3 substituents, which may be the same or different, selected from halogen (for example fluoro or chloro) and alkyl ( 1 -4C) (for example methyl); (sss) Q1 is phenyl bearing 1 or 2 substituents, which may be the same or different, selected from halogen (particularly fluoro and chloro, more particularly fluoro); (tíí) Q1 is selected from 2-fluorophenil and 3-fluorophenil; (uuu) Q is 3-fluorophenyl; (vvv) Q1 is 2-fluorophenyl; (www) Q1 is pyridyl (for example 2-pyridyl or 3-pyridyl) which optionally carries 1 or 2 subsitutes, which may be the same or different, selected from fluoro, chloro, hydroxy, alkyl (1-4C) and alkoxy (1-4C) (particularly alkyl (1-4C), for example methyl); (xxx) Q1 is 2-pyridyl which optionally bears 1 or 2 substituents, which may be the same or different, selected from fluoro, chloro, hydroxy, alkyl (1-4C) and alkoxy (1-4C); (yyy) Q1 is selected from 2-pyridyl, 6-methyl-pyrid-2-yl and 6-methyl-pyrid-3-yl; (zzz) Q1 is 2-pyridyl; (aaaa) Q1 is 6-methyl-pyrid-2-yl; (bbbb) Q1 is 6-methyl-pyridi-3-yl; (cccc) Q1 is 1,3-thiazolyl (for example 1,3-thiazol-2-yl or 1,3-thiazol-4-yl) which optionally carries 1 or 2 subsifluents, which may be the same or different, selected of fluoro, chloro, hydroxy, alkyl (1-4C) and alkoxy (1-4C); (dddd) Q1 is 1,3-thiazol-2-yl; (eeee) Q1 is 1, 3-yiazol-4-yl; (ffff) Q1 is pyrazinyl (for example 2-pyrazinyl) which optionally bears 1 or 2 substituents, which may be the same or different, selected from fluoro, chloro, hydroxy, alkyl (1-4C) and alkoxy (1-4C); (gggg) Q1 is 2-pyrazinyl; (hhhh) Q1 is isoxazolyl (for example 3-isoxazolyl) which optionally carries 1 or 2 substituents, which may be the same or different, selected from fluoro, chloro, hydroxy, alkyl (1-4C) and alkoxy (1-4C) (particularly alkyl (1-4C), for example methyl); (iiii) Q1 is 5-methyl-isoxazol-3-yl; (jjjj) Q1 is selected from phenyl, pyridyl, pyrazinyl, thiazolyl, and soxazolyl (particularly pyridyl, more particularly 2-pyridyl), and wherein Q1 optionally bears 1, 2, or 3 successive, which may be the same or different, selected from fluoro, chloro, hydroxy, cyano, nitro, amino, alkyl (1-4C), alkoxy (1-4C), .N-alkylamino (1-4C) and JN.JN-di- [alkyl (1-4C) )] amino, X1 is selected from OCH2, O (CH3) 2 and O, and n is 0 or 1, R3 when present, is located in the meta position (position 3) relative to the nihologen in the anilino group, where R3 It has any of the values defined above (for example R3 is selected from fluoro, chloro and alkyl (1 -3C) (such as methyl)); (kkkk) Q1 is selected from phenyl, pyridyl, pyrazinyl, thiazolyl and isoxazolyl (particularly pyridyl, more particularly 2-pyridyl), and wherein Q1 optionally carries 1, 2, or 3 substituents, which may be the same or different, selected of fluoro, chloro, hydroxy, cyano, niino, amino, alkyl (1-4C), alkoxy (1-4C), JN-alkylamino (1-4C) and JN, N-di- [alkyl (1-4C)] amino, X1 is O (CH3) 2, and n is O or 1, R3, when present, is located in the meta position (position 3) relative to nitrogen in the anilino group, where R3 has any of the values defined above (for example R3 is selected from fluoro, chloro and alkyl (1 -3C) (such as meily)); (Mil) Q1 is selected from phenyl, pyridyl, pyrazinyl, isoazolyl and isoxazolyl (particularly pyridyl, more particularly 2-pyridyl), and wherein Q1 optionally carries 1, 2, or 3 substituents, which may be the same or different, selected from fluoro, chloro, hydroxy, cyano, nitro, amino, alkyl (1-4C), alkoxy (1-4C), N-alkylamino (1-4C) and JN, JN-di- [alkyl (1-4C) ] amn, X1 is OCH2, and n is O or 1, R3, when present, is located at the meia position (position 3) relative to nitrogen in the anilino group, where R3 has any of the values defined above ( for example R3 is selected from fluoro, chloro and alkyl (1 -3C) (such as methyl)); (mmmm) Q1 is selected from phenyl, pyridyl, pyrazinyl, thiazolyl and isoxazolyl, and wherein Q1 optionally bears 1, 2, or 3 substituents, which may be the same or different, selected from fluoro, chloro, hydroxy, cyano, nitro , amino, alkyl, (1-4C), alkoxy (1-4C), JN-alkylamino (1-4C) and JN.JN-di- [alkyl (1-4C)] amino, X1 is O, and n is 0 or 1, R3, when present, is located in the meta position (position 3) relative to nitrogen in the anilino group, where R3 has any of the values defined above (for example R3 is selected from fluoro, chloro and alkyl ( 1 -3C) (as I entered!)); (nnnn) R4, R4a, R5 and R5a, which may be the same or different, are selected from hydrogen and alkyl (1 -3C) (particularly methyl); (oooo) R4, R4a, R5 and R5a, which may be the same or different, are selected from hydrogen and alkyl (1 -3C) (particularly methyl), wherein at least one of R4, R4a, R5 and R5a is alkyl (1 -3C) (particularly methyl); (pppp) R4, R4a and R5 are all hydrogen and R5a is alkyl (1 -3C) (particularly mefil); (qqq) R4, R5 and R5a are all hydrogen and R5a is alkyl (1 -3C) (paralycally methyl); (rrrr) R4 and R4a are both hydrogen and R5 and R5a are both (1-3C) alkyl (particularly methyl); (ssss) R4a and R5a are both hydrogen; (títf) R 4a, R 5a and R 4 are hydrogen and R 5 is alkyl (1-6C), R 4a, R 5a and R 5 are hydrogen and R 4 is alkyl (1-6C), and wherein any group CH 2 or CH 3 in any of R 4 and R5 and optionally carries in each said group CH2 or CH3 one or more (for example 1, 2 or 3) halogen substituents or a substitute selected from hydroxy and (1-6C) alkoxy; (uuuu) R4 and R4a are hydrogen, R5 and R5a are both alkyl (1-6C), or R5 and R5a are hydrogen, and R4 and R4a are both alkyl (1-6C), and wherein any CH2 or CH3 group in any of R4, R a, R5 and R5a optionally carries in each said group CH2 or CH3 one or more (for example 1, 2 or 3) halogen substituents or a substiuent selected from hydroxy and (1-6C) alkoxy; (vvvv) R5 and R5a are hydrogen, and R4 and R4a together with the carbon atom to which they are attached form a (3-7C) cycloalkyl ring (for example cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl), and wherein any group CH2 or CH3 in any of R4 and R4a optionally carries in each said group CH2 or CH3 one or more (for example 1, 2 or 3) substifuyenfes of halogen or a subsfituyente selected from hydroxy and alkoxy (1 -6C); (wwww) R4 and R4a are hydrogen, and R5 and R5a together with the carbon atom to which they are attached form a (3-7C) cycloalkyl ring (for example cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl), and wherein any group CH2 or CH3 in any of R5 and R5a optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) halogen substituents or a substituted substitution of hydroxy and (1-6C) alkoxy; (xxxx) R4, R4a, R5 and R5a are all hydrogen; (yyyy) R6 is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C) , cycloalkenyl (3-7C), cycloalkenyl (3-7C) -alkyl (1-6C), heterocyclyl and heterocyclyl-alkyl (1-6C), and wherein any heterocyclyl group in a substituent R6 optionally bears one or more substituents, which may be the same or differentiated, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C) ), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, (2-6C) alkanoyl, alkanoyloxy (2-6C) and a group of the formula: -X3-R10 wherein X3 is a direct bond or is selected from O and N (R11), wherein R1 1 is hydrogen or alkyl (1-4C), and R1 0 is halogen-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1 - 4C), N-alkylamino (1 - 4C) -alkyl (1-4C) and N, N-di- [alkyl (1-4C)] amino-alkyl (1-4C), and wherein any heterocyclyl group in a substituent R6 optionally carries 1 or 2 oxo substituents; and wherein any CH2 or CH3 group in a substituent R6, other than a CH2 group in a heyerocyclyl group, optionally bears in each said CH2 or CH3 group one or more halogen substituents or alkyl (1-6C) or a substituent selected from hydroxy, amino, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkyltolium (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1 - 6C) and di- [alkyl (1 -6C)] amino; (zzzz) R6 is selected from hydrogen, alkyl (1-6C), hydroxy-alkyl (2-6C), alkoxy (1-6C) -alkyl (2-6C), halogen-alkyl (2-6C), amino-alkyl (2-6C), N-alkylamino (1-6C) -alkyl (1 -6C), N, Nd - [alkyl (1-6C)] amino-alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalkyl (3C) -7C) -alkyl (1-6C), heterocyclyl and heterocyclyl-alkyl (1-6C), and wherein any heterocyclyl group in a substituent R6 optionally bears one or more sub-bases, which may be the same or different, selected from halogen, trifluoromethyl, cyano, niiro, hydroxy, amino, mercapio, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkyl (1-6C) ), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C)] amino, alkanoyl (2-6C), alkanoyloxy (2-6C) and a group of the formula: -X3-R10 wherein X3 is a direct bond or is selected from O and N (R1 1), wherein R11 is hydrogen or alkyl (1-4C), and R10 is halo-alkyl (1 -4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C), JN-alkylamino (1 -4C) -alkyl (1-4C) and N, N-di- [(1-4C) alkyl] amino-alkyl (1-4C), and wherein any heterocyclyl group in a substituent R6 optionally carries 1 or 2 substitutents oxo; (aaaaa) R6 is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C) , heyerocyclyl and heterocyclyl (1-6C) alkyl, wherein any heterocyclyl group in R6 is a 4, 5, 6 or 7 member partially saturated or saturated monocyclic heterocyclyl ring containing 1 or 2 heteroatoms selected from oxygen, nitrogen and sulfur , and wherein any heterocyclyl group in a substituent R6 optionally carries one or more substifuyeníes, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C)] amino, alkanoyl (2-6C), alkanoyloxy (2-6C) and a group of the formula: -X3-R 10 wherein X3 is a direct bond or is selected from O and N (R11), wherein R11 is hydrogen or alkyl (1-4C), and R10 is halo-alkyl (1-4C), hydroxy-alkyl (1-4C) ), (1-4C) alkoxy-(1-4C) alkyl, cyano (1-4C) alkyl, amino (1-4C) alkyl, N-alkylamino (1-4C) -alkyl (1-4C) and N, N-di- [(1-4C) alkyl] amino-alkyl (1-4C), and wherein any heterocyclyl group in a substituent R6 optionally carries 1 or 2 oxo substituys; and wherein any CH2 or CH3 group in a SUBSTITUTE R6, other than a CH2 group in a heterocyclyl group, optionally carries in each said CH2 or CH3 group one or more halogen substituents or alkyl (1-6C) or a substitute selected from hydroxy, amino, (1-6C) alkoxy, (1-6C) alkylamino, and di- [(1-6C) alkyl] amino; (bbbbb) R6 is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C) , heyerocyclyl and heterocyclyl-alkyl (1-6C), wherein any heterocyclyl group in R6 is a partially salified or saturated monocyclic 4, 5, 6 or 7 membered hephecyclic ring containing 1 or 2 selected oxygen, nitrogen and sulfur compounds , such a heterocyclyl group is linked to the group to which it is attached by an annular carbon atom, and wherein any heterocyclyl group in a substituent R6 optionally carries one or more substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C) ), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(C 1-6C)] amino, alkanoyl (2-6C), alkanoyloxy (2-6C) and a group of the formula: X3-R10 in where X3 is a direct bond or is selected from O and N (R11), wherein R11 is hydrogen or alkyl (1-4C), and R10 is halo-alkyl (1-4C), hydroxy-alkyl (1-4C) , (1-4C) alkoxy-alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C), N-alkylamino (1-4C) -alkyl (1-4C) and N , JN-d1- [(1-4C) alkyl] amino-alkyl (1-4C), and wherein any hephecyclicyl group in a substituent R6 optionally carries 1 or 2 oxo substituents; and wherein any CH2 or CH3 group in a substituent R6, other than a CH2 group in a heterocyclyl group, optionally carries in each said CH2 or CH3 group one or more halogen substituents or alkyl (1-6C) or a substitute selected from hydroxy, amino, (1-6C) alkoxy, alkylamino (1-6C) and di- [(C 1-6C)] amino; (cecee) R6 is selected from hydrogen, alkyl (1 -3C), alkenyl (2-3C), alkynyl (2-3C), cycloalkyl (3-5C), cycloalkyl (3-5C) -alkyl (1 -3C) , heterocyclyl and heterocyclyl-alkyl (1 -3C), wherein any heterocyclyl group in R6 is a partially saturated, saturated or monocyclic saturated heterocyclyl ring of 4, 5, 6 or 7 members with 1 or 2 selected heteroarylnes of oxygen, nitrogen and sulfur , such heterocyclyl group is linked to the group to which it is attached by an annular carbon atom, and wherein any heterocyclic group in a sub-R6 optionally carries one or more substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C) ), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(C 1-6C)] amino, alkanoyl (2-6C), alkanoyloxy (2-6C) and a group of the formula: R 0 wherein X3 is a direct bond or is selected from O and N (R1 1), wherein R1 1 is hydrogen or alkyl (1-4C), and R10 is halo-alkyl (1-4C), hydroxy-alkyl (1 -4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C), JN-alkylamino (1-4C) -alkyl (1-4C) ) and JN, JN-di- [alkyl (1-4C)] amino-alkyl (1-4C), and wherein any heterocyclyl group in a substituent R6 optionally bears 1 or 2 substituents oxo; and wherein any CH2 or CH3 group in a substituent R6, other than a CH2 group in a hemerocyclyl group, optionally carries in each said CH2 or CH3 group one or more halogen substituents or alkyl (1-6C) or a substituent selected from hydroxy, amino, (1-6C) alkoxy, (1-6C) alkylamino, and di- [(1-6C) alkyl] amino; (ddddd) R6 is selected from hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, vinyl, isopropenyl, butyl, but-2-enyl, ethynyl, 2-propynyl, butynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, pyrrolinyl, pyrrolidinyl, piperidinyl, homopiperidinil, homopiperazinyl, dihydropyridinyl, tetrahydropyridinyl, dihidropirimidinil, tetrahydropyrimidinyl, tetrahydrothienyl, íetrahidrotiopiranil, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, ciclohexilmeíil, 2-ciclopropileíil, 2-ciclobutiletil, 2-cyclopentylethyl, 2- cyclohexylethyl, azetidinilmeíil, pirrolinilmetil, pyrrolidinylmethyl, morpholinylmethyl, piperidinylmethyl, homopiperidinilmetil, piperazinilmeíil, homopiperazinilmetil, dihidropiridinilmeíil, tetrahidropiridinilmetil, dihidropirimidinilmetil, tetrahidropirimidinilmetil, íetrahidrotienilmetil, teírahidrotiopiranilmetil, tiomorfolinilmetil, tetrahydrofuranylmethyl, tetrahidropiranilmetil, 2- (azetidinyl) ethyl, 2- (p irroliniI) ethyl, 2- (pyrrolidinyl) ethyl, 2- (morpholinyl) ethyl, 2- (piperidinyl) ethyl, 2- (homopiperidinyl) ethyl, 2- (piperazinyl) ethyl, 2- (homopiperazinyl) ethyl, 2- (dihydropyridinyl ) ethyl, 2- (tetrahydropyridinyl) etiI, 2- (dihydropyrimidinyl) ethyl, 2- (tetrahydropyrimidinyl) ethyl, 2- (tetrahydroiienyl) ethyl, 2- (tetrahydropylopyranyl) ethyl, 2- (thiomorpholinyl) ethyl, 2- (tetrahydrofuranyl) ethyl, 2- (tetrahydropyranyl) eyl, and wherein any CH2 or CH3 group in a substituent R6, other than a CH2 group in a heterocyclyl group, optionally bears in each said CH2 or CH3 group one or more sub -ifluids, which may be the same or differentiated, selected from fluoro, chloro, bromo, methyl, ethyl, propyl and isopropyl, or a substituent selected from hydroxy, amino, methoxy, ethoxy, methylamino, eylamino, di-methylamino, di-ethylamino and JN-methyl-JN -ethylamino, and where any heterocyclyl group in R6 optionally carries one or more sub-groups, which may be the same or different, selected from fluoro , chlorine, bromine, oxo, hydroxy, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, trifluoromethyl, vinyl, isopropenyl, allyl, but-2-enyl, ethynyl, 2-propynyl, butynyl, methoxy, ethoxy, propoxy, isopropoxy , trifluoromethoxy, acetyl, propionyl, hydroxymethyl, methoxymethyl, ethoxymethyl, 2-hydroxyethyl, 2-methoxyethyl and 2-ethoxyethyl; (eeeee) R6 is selected from hydrogen, methyl, ethyl, 2-hydroxyethyl, 2-methoxyethyl, propyl, 3-hydroxypropyl, 2-hydroxypropyl, 3-meioxypropyl, 2-methoxypropyl, isopropyl, vinyl, isopropenyl, allyl, but-2 -enyl, ethynyl, 2-propynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, pyrrolinyl, pyrrolidinyl, piperidinyl, homopiperidinyl, tetrahydrofuranyl, iorahydropyranyl, cyclopropylmethyl, cyclobuylmethyl, cyclopentylmethyl, cyclohexylmethyl, 2-cyclopropylethyl, 2-cyclobutylethyl, 2-cyclopentyleryl , 2-cyclohexylethyl, azetidinylmethyl, pyrrolidinylmethyl, piperidinylmethyl, homopiperidinylmethyl, tetrahydroiopyranylmethyl, tetrahydrofuran and methyl, tetrahydropyranylmethyl, 2- (azetidinyl) ethyl, 2- (pyrrolidinyl) ethyl, 2- (piperidinyl) ethyl, 2- (homopiperidinyl) ethyl , 2- (tephrahydrothienyl) ethyl, 2- (tetrahydroiopyranyl) efil, 2- (thiomorpholinyl) ethyl, 2- (tetrahydrofuranyl) ethyl and 2- (teirahydropyranyl) efil, and wherein any CH2 group in a cycloalkyl group in R6 optionally bears In cad to CH2 group 1 or 2 substituents selected from hydroxy, methyl, ethyl, methoxy and eioxy, and wherein any CH2 or CH3 group in a R6 substituent, differentiates a CH2 group in a heterocyclyl group, optionally bears in each said CH2 group or CH3 one or more fluoro substituents, and wherein any heterocyclyl group in R6 optionally bears one or more substituents, which may be the same or different, selected from fluoro, chloro, bromo, oxo, hydroxy, methyl, ethyl, propyl, isopropyl , trifluoromethyl, methoxy, eioxy, propoxy, isopropoxy and ureaifluoromethoxy; (fffff) R6 is selected from hydrogen, methyl, ethyl, 2-hydroxyethyl, 2-methoxyethyl, propyl, 3-hydroxypropyl, 2-hydroxypropyl, 3-methoxypropyl, 2-methoxypropyl, isopropyl, allyl, bu-2-enyl, 2-propynyl, cyclopropyl, cyclobutyl, cyclopenyl, cyclohexyl, azetidinyl, pyrrolinyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, cyclopropylmethyl, cyclobutylmethyl, cyclopenylmethyl, cyclohexylmethyl, 2-cyclopropyleryl, 2-cyclobutylethyl , 2-cyclopentyleryl, 2-cyclohexylethyl, azetidinylmethyl, pyrrolidinylmethyl, piperidinylmethyl, teirahydrofuranylmethyl, 1-tetrahydropyranylmethyl, 2- (azetidinyl) ethyl, 2- (pyrrolidinyl) ethyl, 2- (piperidinyl) ethyl, 2- (tefrahydrofuranyl) efil and 2- ( tetrahydropyranol) etl, and wherein any CH2 group in a cycloalkyl group in R6 optionally carries in each CH2 group 1 or 2 substituents selected from hydroxy, methyl, ethyl, methoxy and ethoxy, and wherein any heterocyclyl group in R6 optionally it carries one or more substituents, which may be the same or different, selected from fluoro, chloro, bromo, oxo, hydroxy, methyl, ethyl, propyl, isopropyl, trifluoromethyl, methoxy, ethoxy, propoxy, isopropoxy and trifluoromethoxy; (99999) R6 is selected from hydrogen, methyl, ethyl, 2-hydroxyethyl, 2-methoxyethyl, propyl, isopropyl, allyl, 2-propynyl, cyclopropyl, cyclobutyl, piperidinyl, tetrahydropyranyl and cyclopropylmethyl, and wherein any CH2 group in a group cycloalkyl in R6 optionally carries in each CH2 group 1 or 2 substituents selected from hydroxy, methyl, eyl, meioxy and eioxy, and wherein any heterocyclyl group in R6 optionally bears one or more substifuyeníes, which may be the same or different, selected from fluoro, chloro, bromo, oxo, hydroxy, methyl, ethyl, propyl, sopropyl, trifluoromethyl, methoxy, eioxy, propoxy, isopropoxy and trifluoromethoxy; (hhhhh) R6 is selected from hydrogen and alkyl (1 -3C) (e.g.

R6 is hydrogen or methyl); (iiiii) R6 is hydrogen; (jjjjj) R 6 is alkyl (1 -3C) (for example methyl); (kkkkk) R6 is alkyl (1 -3C), and wherein any CH2 or CH3 group in a substituent R6, differentiates a CH2 group in a ring of heterocyclic, optionally carries in each said group CH2 or CH3 one or more selected substituents of hydroxy and (1-6C) alkoxy (for example methoxy); (Mill) R6 is alkenyl (2-6C) (for example allyl); (mmmmm) R6 is alkynyl (2-6C) (for example 2-propynyl); (nnnnn) R6 is selected from cycloalkyl (3-7C) and cycloalkyl (3-7C) -alkyl (1-6C) (for example R6 is selected from cyclopropyl, cyclobuyl, cyclopropylmethyl and cyclobuhyl-mephyl); (ooooo) R6 is heterocyclyl (for example R6 is selected from piperidinyl and tetrahydropyranyl); (ppppp) A is selected from a group of the formula Z- (CR12R13) P- and R14, wherein p is 1, 2, 3, or 4, each R12 and R13, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl (2) -6C), or a group R12 and R13 linked to the same carbon atom form a cycloalkyl (3-7C) ring or cycloalkenyl (3-7C), and wherein any CH2 or CH3 group in any of R2 and R13 optionally bears in each said group CH2 or CH3 one or more (for example 1, 2 or 3) substiuyenyes of halogen or alkyl (1-6C) or a substituent selected from hydroxy, cyano, alkyl (1-6C), alkoxy (1-6C) ), amino, alkanoyl (2-6C), alkylamino (1-6C) and di- [(1-6C) alkyl] amino, Z is selected from hydrogen, OR15, NR16R17 and alkylsulfonyl (1-6C), wherein each of R 5, R 16 and R 17, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C) and alkoxycarbonyl (1-6C) , R14 is selected from OR1 9 and NR16R17, wherein R19 is selected from alkyl (1-6C), alkenyl (2-6C) and alkynyl (2-6C) ), and wherein R16 and R17 are as defined above, or R14 is Q4 wherein Q4 is cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C), cycloalkenyl (3-7C), cycloalkenyl (3-7C) -alkyl (1-6C), heterocyclyl or heterocyclyl-alkyl (1-6C), and wherein adjacent carbon atoms in any alkylene chain (2-6C) in a substituent Z or R14 are separated optionally by the insertion in the chain of a selected group of O, S, SO, SO2, N (R21), CO, -C = C- and -C = C-, wherein R21 is hydrogen or alkyl (1-6C) ), and wherein any heterocyclic group in a substituent Z or R14 optionally carries one or more (for example 1, 2 or 3) substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl ( 1 -6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, (2-6C) alkanoyl, alkanoyloxy (2-6) C) and a group of the formula: -X6-R22 wherein X6 is a direct bond or is selected from O, CO, SO2 and N (R23), wherein R23 is hydrogen or alkyl (1-4C), and R22 is halogen-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C) ), N-alkylamino (1-4C) -alkyl (1-4C), and JN, N-di [(1-4C) alkyl] amino-alkyl (1-4C), and wherein any heterocyclyl group in a Substituent Z or R14 optionally bears 1 or 2 substitutes oxo or ioxo, and wherein any group CH2 or CH3 in a group Z or R14, other than a group CH2 in a heterocyclyl ring, optionally carries in each said group CH2 or CH3 one or more halogen substituents or (1-6C) alkyl or a substituent selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, JN-alkylcarbamoyl (1-6C), N , J __- di [alqu il (1-6C)] carbamoyl, alkanoyl (2-6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), N-alkyl (1-6C) -alkanoylamino (2-6C), JN-alkylsulfamoyl ( 1-6C), N, N-di [alkyl (1-6C)] sulfamoyl, alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C); (qq) A is selected from a group of the formula Z- (CR 2 R 13) P- and R 14, wherein p is 1, 2 or 3, each R 12 and R 13, which may be the same or different, is selected from hydrogen and alkyl (1-6C), or a group R12 and R13 attached to the same carbon atom form a cycloalkyl (3-7C) ring, and wherein any CH2 or CH3 group in any of R12 and R13 optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) substitutents of halogen or alkyl (1-6C) or a subsituitute selected from hydroxy, cyano, alkyl (1-6C) and alkoxy (1-6C), Z is selected from hydrogen, OR15, NR16R17 and alkylsulfonyl (1-6C), wherein each of R15, R1, and R17, which may be the same or different, is selected from hydrogen, alkyl (1-6C), and alkoxycarbonyl (1-6C), R14 is selected from OR19 and NR16R17, wherein R19 is selected from alkyl (1-6C), and wherein R16 and R17 are as defined above, or R14 is Q4 wherein Q4 is cycloalkyl (3 -7C), cycloalkyl (3-7C) -alkyl (1 -6C), heteroaryl or heterocyclyl-alkyl (1-6C), and wherein adjacent carbon atoms in any alkylene chain (2-6C) in a substituent Z or R14 are optionally separated by the insertion in the chain of a group selected from O, S, SO, SO2, N (R21), CO, -C = C- and -C = C-, wherein R21 is hydrogen or alkyl (1-6C), and wherein any heterocyclic group in a substituent Z or R14 optionally bears one or more (for example 1, 2 or 3) substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl ( 1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkyl (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino ( -6C), di- [(1-6C) alkyl] amino, (2-6C) alkanoyl, (2-6C) alkanoyloxy and a group of the formula: -X6-R22 wherein X6 is a direct bond or selects from O, CO, SO2 and N (R23), wherein R23 is hydrogen or alkyl (1-4C), and R22 is halogen-alkyl (1 -4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C), N-alkylamino (1 -4C) -alkyl (1-4C), and JN, JN-di [alkyl (1-4C)] amino-alkyl (1-4C), and wherein any heyerocyclyl group in a substituent Z or R14 optionally carries 1 or 2 oxo or thioxo substituents, and wherein any CH2 or CH3 group in a group Z or R14, other than a CH2 group in a heterocyclyl ring, optionally carries in each said group CH2 or CH3 one or more substituents of halogen or alkyl ( 1-6C) or a substituent selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinil (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(C 1-6C)] amino, JN-alkylcarbamoyl (1-6C), N, N-di [alkyl (1 -6C)] carbamoyl, alkanoyl (2-6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), JN-alkyl (1-6C) -alkanoylamino (2-6C), JN-alkylsulfamoyl (1-6C) ), N, N-di [alkyl (1-6C)] sulfamoyl, alkanesu lfonylamino (1-6C) and N.- (1-6C) alkyl-alkanesulfonylamino (1-6C); (rrrrr) A is selected from a group of the formula Z- (CR12R13) P- and R14, where p is 1, 2 or 3 (particularly 1 or 2), each R12 and R13, which may be the same or different , is selected from hydrogen and alkyl (1-6C), and wherein any CH2 or CH3 group in any of R12 and R13 optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) substituents of halogen or a substituent selected from hydroxy and (1-6C) alkoxy (particularly hydroxy), Z is selected from hydrogen, OR15, NR16R17 and alkylsulfonyl (1-6C), wherein each of R15, R16 and R17, which may be the same or differentiate, is selected from hydrogen, alkyl (1-6C), and alkoxycarbonyl (1-6C), R14 is selected from OR19 and NR16R17, wherein R19 is selected from alkyl (1-6C), and wherein R16 and R17 are as defined above, or R14 - is Q4 wherein Q4 is cycloalkyl (3-7C), heterocyclyl or heterocyclyl-alkyl (1-6C), and wherein any heterocyclyl group on a substituent Z or R14 opc It optionally carries one or more (for example 1, 2 or 3) substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapio, alkyl (1-6C), alkenyl (2-6C), (2-6C) alkynyl and (1-6C) alkoxy, and wherein any CH2 or CH3 group in a Z or R14 group, other than a CH2 group in a heterocyclyl ring, optionally carries in each said CH2 or CH3 group one or more substituents of halogen or alkyl (1-6C) or a substiuent selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C) and alkoxy (1-6C); (ssss) A is selected from a group of the formula Z- (CR12R13) P- and R14, where p is 1, 2 or 3 (particularly 1 or 2), each R12 and R1 3 that can be the same or different, is selected from hydrogen and alkyl (1-6C), and wherein any CH2 or CH3 group in any of R12 and R13 optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) substitutes of halogen or a substituent selected from hydroxy and (1-6C) alkoxy (particularly hydroxy), Z is selected from hydrogen, OR15, NR16R17 and alkylsulfonyl (1-6C), wherein each of R1 5, R16 and R17, which can be the same or different, it is selected from hydrogen, alkyl (1-6C), and alkoxycarbonyl (1-6C), R14 is selected from OR19 and NR16R17, wherein R19 is selected from alkyl (1-6C), and wherein R16 and R17 are as defined above, or R14 is Q4 wherein Q4 is cycloalkyl (3-7C), heterocyclyl or heterocyclyl-alkyl (1-6C), and wherein any heterocyclyl group in a substituent Z or R14 optionally bears one or more (for example 1, 2 or 3) substituents, which may be the same or different, selected from halogen, hydroxy, alkyl (1-6C) and alkoxy (1-6C) (p. Alkyl (1-6C), and wherein any CH2 or CH3 group in a group Z or R14, other than a CH2 group in a heterocyclic ring, optionally carries in each said group CH2 or CH3 one or more halogen subsitutes or alkyl (1-6C) or a substituent selected from hydroxy and (1-6C) alkoxy (particularly a substituent selected from halogen and hydroxy); (tííft) A is selected from a group of the formula Z- (CR12R13) P- and R14, where p is 1, 2, 3, or 4, each R12 and R13 which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl (2-6C), or a group R12 and R13 attached to the same carbon atom form a ring of cycloalkyl (3-7C) or cycloalkenyl (3-) 7C), and wherein any CH2 or CH3 group in any of R12 and R13 optionally carries in each said group one or more (for example 1, 2 or 3) halogen or alkyl (1-6C) substituents or a substituent selected from hydroxy, cyano, alkyl (1-6C), alkoxy (1-6C), amino, alkanoyl (2-6C), alkylamino (1-6C) and di- [alkyl (1-6c)] amino, and wherein Z is selected from hydrogen, OR15, NR16R17, wherein each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl ( 2-6C), and where R14 is Q4 where Q4 is heterocyclyl, and where adjacent carbon atoms in C Any alkylene chain (2-6C) in a substituent Z or R14 are optionally separated by the insertion in the chain of a group selected from O, S, SO, SO2, N (R21), CO, -C = C- y- C = C-, where R21 is hydrogen or alkyl (1-6C), and wherein any heterocyclyl group in a substituent R14 optionally carries one or more (for example 1, 2 or 3) substituents, which may be the same or different, selected from halogen, trifluoromethyl , cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl ( 1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(C 1-6C)] amino, alkanoyl (2-6C), alkanoyloxy (2-6C) and a group of the formula: X6-R22 wherein X6 is a direct bond or is selected from O, CO, SO2 and N (R23), wherein R23 is hydrogen or alkyl (1-4C), and R22 is halo-alkyl (1-4C) ), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C), JN-alkylamino (1-4C) ) -alkyl (1-4C), and N, N-di [(1-4C) alkyl] amino-alkyl (1-4C), and wherein any heterocyclyl group in a R14 substituent optionally carries 1 or 2 substituents oxo, and where Any group CH2 or CH3 in a substituent Z or R14, different from a group CH2 in a heterocyclyl ring, optionally carries in each said group CH2 or CH3 one or more substituents of halogen or alkyl (1-6C) or a substituent selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1 -6C), alkylamino, di- [(1-6C) alkyl] amino, JN-alkylcarbamoyl (1-6C), N, l __- di [alk (1-6C)] carbamoyl, alkanoyl (2-6C) , alkanoyloxy (2-6C), alkanoylamino (2-6C), N-alkyl (1-6C) -alkylamino (2-6C), N-alkylsulfamoyl (1-6C), NN-di [alkyl (1-6C) ] sulfamoyl, alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C); (uuuuu) A is selected from a group of the formula Z- (CR12R 3) P- and R14, wherein p is 1 or 2, each R12 and R13, which may be the same or different, is selected from hydrogen and alkyl (1-6C), or a group R12 and R13 attached to the same carbon atom form a ring of cycloalkyl (3-7C), and wherein any group CH2 or CH3 in any of R12 and R13 optionally carries in each said group CH2 or CH3 one or more of (for example 1, 2 or 3) substituents of halogen or alkyl ( 1-6C) or a substituent selected from hydroxy and (1-6C) alkoxy, and wherein Z is selected from hydrogen, OR15, NR16R17, wherein each of R1 5, R16 and R17, which may be the same or different, it is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl (2-6C), and wherein R14 is Q4 wherein Q4 is a monocyclic heterocyclic ring partially saturated or unsaturated of 4, 5, 6 or 7 members containing 1 nitrogen or oxygen heterogeneous and optionally 1 additional heteroatom selected from oxygen, nitrogen and sulfur, and where Q4 optionally carries one or more (for example 1, 2 or 3) subsymiyenyes, which may be the same or differentiated, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, mercapto, alkyl (1-6C), alkenyl (2-6C) ), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [alkyl (1 -6C)] amino, (2-6C) alkanoyl, (2-6C) alkanoyloxy, and a group of the formula: -X6-R22 wherein X6 is a direct bond or is selected from O and N (R23), where R23 is hydrogen or alkyl (1-4C), and R22 is halo-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C), N-alkylamino (1-4C) -alkyl (1-4C), and N, JN-di [(1-4C) alkyl] amino-alkyl (1 -4C), and wherein Q4 optionally carries 1 or 2 oxo substituents, and wherein any CH2 or CH3 group in a Z or R14 group, other than a CH2 group in a heterocyclyl ring, optionally carries in each said group one or more substiuuyenie Halogen or alkyl (1-6C) or a selected substitution of hydroxy, cyano, amino, alkoxy (1 -6C), alkylamino (1 -6C) and di- [(1-6C) alkyl] amino; (vvvvv) A is selected from a group of the formula Z- (CR12R13) P- and R14, where p is 1, 2 or 3 each R12 and R13, which may be the same or different, is selected from hydrogen and alkyl (1-6C), or a group R12 and R13 attached to the same carbon atom form a cycloalkyl ring (3-7C) ), and wherein any CH2 or CH3 group in any of R12 and R13 optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) halogen or alkyl (1-6C) substituents or a substiuent selected from hydroxy and (1-6C) alkoxy, and wherein Z is selected from hydrogen, OR15, NR16R17, wherein each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl ( 1 -6C), alkenyl (2-6C) and alkynyl (2-6C), and wherein R14 is Q4 wherein Q4 is a partially saturated or saturated monocyclic heterocyclic ring of 4, 5, 6 or 7 members containing 1 heyeroatomo of niógeno or oxygen and optionally 1 additional heteroaphome selected from oxygen, nitrogen and sulfur, such ring bound to the carbonyl group in the formula to I for an annular carbon atom, and wherein Q4 optionally bears one or more (for example 1, 2 or 3) subsfifuyenfes, which may be the same or differentiated, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino , mercapio, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C) ), alkylamino (1-6C), di- [(1-6C) alkyl] amino, (2-6C) alkanoyl, (2-6C) alkanoyloxy and a group of the formula: -X6-R22 wherein X6 is a direct bond or is selected from O and N (R23), wherein R23 is hydrogen or alkyl (1-4C), and R22 is halogen-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy ( 1 -4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C), JN-alkylamino (1-4C) -alkyl (1-4C), and JN. N.-di [alkyl (1-4C)] amino-alkyl (1-4C), and wherein Q4 optionally carries 1 or 2 oxo substituents, and wherein any CH2 or CH3 group in a group Z or R14, different from a CH2 group in a heterocyclyl ring, optionally carries in each said CH2 or CH3 group one or more halogen or alkyl (1-6C) substitutes or a subsituitute selected from hydroxy, cyano, amino, (1-6C) alkoxy, alkylamino (1 -6C) and di- [alkyl (1 -6C)] amino; (wwwww) A is a group of the formula Z- (CR12R13) P-, where p is 1 or 2; each R12 and R13, which may be the same or different, is selected from hydrogen and alkyl (1-6C), or a group R12 and R13 attached to the same carbon atom form a cycloalkyl ring (3-7C), and in wherein Z is selected from hydrogen, OR 5, NR16R17 and alkylsulfonyl (1-6C), wherein each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-6C) and alkoxycarbonium (1-6C), and wherein any group CH2 or CH3 in any of R12, R13 and Z, optionally carries in each said group CH2 or CH3 one or more (for example 1, 2 or 3) halogen or alkyl substituents (1-6C) or a substiuent selected from hydroxy and (1-6C) alkoxy; (xxxxx) A is a group of the formula Z- (CR12R13) P-, where p is 1 or 2, each R12 and R13, which may be the same or different, is selected from hydrogen and alkyl (1-6C) , and wherein Z is selected from hydrogen, OR15, NR 6R17 and alkylsulfonyl (1-6C), wherein each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1 - 6C) and alkoxycarbonyl (1-6C), and wherein any CH2 or CH3 group in any of R12, R13 and Z, optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) substituents of halogen, alkyl (1-6C) or hydroxy; (yyyyy) A is a group of the formula Z- (CR12R13) P-, where p is 1 or 2, each R12 and R13, which may be the same or different, is selected from hydrogen and alkyl (1-6C) , or a group R12 and R13 attached to the same carbon atom form a cycloalkyl ring (3-7C), and wherein Z is selected from hydrogen, OR15, NR16R17, wherein each of R15, R16 and R17, which can be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl (2-6C), and wherein any group CH2 or CH3 in any of R12, R13 and Z, optionally it carries in each said group CH2 or CH3 one or more (for example 1, 2 or 3) substituents of halogen or alkyl (1-6C) or a substituent selected from hydroxy and (1-6C) alkoxy; (zzzzz) A is a group of the formula Z- (CR12R13) P-, where p is 1 or 2, each R12 and R3, which may be the same or different, is selected from hydrogen and alkyl (1-4C) ), or a group R12 and R1 3 attached to the same carbon atom form a cycloalkyl ring (3-6C), and wherein Z is selected from hydrogen and OR15, wherein R15 is selected from hydrogen and alkyl (1-6C) ), and wherein any CH2 or CH3 group in any of R12, R13 and Z, optionally bears in each said CH2 or CH3 group one or more (for example 1, 2 or 3) halogen or alkyl (1-4C) substituents or a substituent selected from hydroxy and (1-4C) alkoxy; (aaaaaa) A is a group of the formula Z- (CR12R13) P-, where p is 1 or 2, each R12 and R13, which may be the same or different, is selected from hydrogen and alkyl (1-4C) , or a group R12 and R13 attached to the same carbon atom form a cycloalkyl ring (3-6C), and wherein any CH2 or CH3 group in any of R12 and R13 optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) substituents of halogen or alkyl (1-4C) or a substitute selected from hydroxy and (1-4C) alkoxy, and wherein Z is hydroxy; (bbbbbb) A is a group of the formula Z- (CR12R13) P-, where p is 1 or 2, each R12 and R13, which may be the same or different, is selected from hydrogen and alkyl (1-4C) , or a group R12 and R13 linked to the same carbon atom form a cycloalkyl ring (3-7C), and wherein Z is NR16R17, wherein each of R16 and R17, which may be the same or different, is selected of hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl (2-6C), and wherein any group CH2 or CH3 in any of R12, R13 and Z, optionally bears in each said group CH2 or CH3 one or more (for example 1, 2 or 3) substituents of halogen or alkyl (1-6C) or a substituent selected from hydroxy and (1-6C) alkoxy; (cccccc) A is a group of the formula Z- (CR12R13) P-, where p is 1 or 2, each R12 and R13, which may be the same or different, is selected from hydrogen and alkyl (1-4C) , or a group R12 and R13 attached to the same carbon atom form a cycloalkyl ring (3-6C), stipulating that (i) at least one of the groups R12 and R13 is alkyl (1-4C), or that (ii) ) a group R12 and R13 linked to the same carbon atom form a cycloalkyl ring (3-6C), and wherein Z is selected from hydrogen, OR15, NR16R17 and alkylsulfonyl (1-6C), wherein each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C) and alkoxycarbonyl (1-6C), and wherein any group CH2 or CH3 in any of R12, R13 and Z, optionally carries in each said group CH2 or CH3 one or more (for example 1, 2 or 3) substituyees of halogen or alkyl (1-6C) or a subsituitute selected from hydroxy and alkoxy (1-6C); (dddddd) A is a group of the formula Z- (CR12R 3) P-, where p is 1 or 2, each R12 and R13, which may be the same or different, is selected from hydrogen and alkyl (1-4C) ), or a group R12 and R13 linked to the same carbon atom form a cycloalkyl ring (3-6C), stipulating that (i) at least one of the groups R12 and R1 3 is alkyl (1-4C), or ( ii) that a group R12 and R13 bonded to the same carbon atom form a cycloalkyl ring (3-6C), and wherein Z is selected from hydrogen, OR15, NR16R17, wherein each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), and alkynyl (2-6C), and wherein any group CH2 or CH3 in any of R12, R13 and Z, optionally carries in each said group CH2 or CH3 one or more of (for example 1, 2 or 3) substituents of halogen or alkyl (1-6C) or a substituent selected from hydroxy and (1-6C) alkoxy; (eeeeee) A is R14, wherein R14 is selected from OR19 and NR 6R17, wherein each of R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2) -6C), alkynyl (2-6C) and alkoxycarbonyl (1-6C), and wherein R1 9 is selected from alkyl (1 -6C), alkenyl (2-6C) and alkynyl (2-6C), or R14 is Q4 wherein Q4 is cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1 -6C), cycloalkenyl (3-7C), cycloalkenyl (3-7C) -alkyl (1 -6C), heterocyclyl or heterocyclyl-alkyl (1-6C), and wherein adjacent carbon atoms in any alkylene chain (2-6C) in a group R14 are optionally separated by the insertion in the chain a group is selected from O, S, SO, SO2, N (R21), CO, -C = C- and -C = C-, wherein R21 is hydrogen or alkyl (1-6C), and wherein any heterocyclic group in an optional R14 group carries one or more (for example 1, 2 or 3) substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl ( 2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino, di- [(1-6C) alkyl] amino, alkanoyl ( -6C), alkanoyloxy (2-6C) and a group of the formula: -X6-R22 wherein X6 is a direct bond or is selected from O, CO, SO2 and N (R23), wherein R23 is hydrogen or alkyl (1-4C), and R22 is halo-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C) , amino-alkyl (1-4C), N-alkylamino (1-4C) -alkyl (1-4C), and JN, N.-di [(1-4C) alkyl] amino-alkyl (1-4C), and wherein any heterocyclic group in an optional R14 group carries 1 or 2 thiox substituents or oxo, and wherein any CH2 or CH3 group in a group R14, other than a CH2 group in a heterocyclyl ring, optionally bears in each said CH2 or CH3 group one or more halogen or alkyl (1-6C) subsifluents or a substituent selected from hydroxy, cyano, amine, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C) , alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, JN-alkylcarbamoyl (1-6C), N, N-di [(1-6C) alkyl] carbamoyl , alkanoyl (2-6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), N-alkyl (1-6C) -alkanoylamino (2-6C), JN-alkylsulfamoyl (1-6C), N, N -di [alkyl (1-6C)] sulfamoyl, alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C); (ffffff) A is R14, wherein R14 is selected from OR19 and NR16R17, wherein each of R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-6C) and alkoxycarbonyl (1-) 6C), and wherein R19 is selected from alkyl (1-6C), or R14 is Q4 wherein Q4 is cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1 -6C), heterocyclyl or heterocyclyl-alkyl (1-6C), and wherein any heterocyclyl group in a R14 group optionally carries one or more (eg, 1, 2 or 3) substituents, which may be the same or different , selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C) and alkoxy (1-6C), and wherein any heterocyclyl group in an R14 group optionally carries 1 or 2 sub-bases fioxo or oxo, and wherein any CH2 or CH3 group in a group R14, differentiates a CH2 group in a heterocyclyl ring, optionally carries in each said group CH2 or CH3 one or more substitute halogen or alkyl (1 -6C) or a substituted substituyefe of hydroxy and (1-6C) alkoxy; (gg ggg) is R14 'wherein R14 is OR19, wherein R1 9 is alkyl (1-6C) (particularly alkyl (1 -3C), such as methyl); (hhhhhh) A is R14, where R14 is NR16R17, where each of R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-6C) and alkoxycarbonyl (1-6C), and wherein any CH2 or CH3 group in a group R16 or R17, optionally carries in each said CH2 or CH3 group one or more substituents of halogen or alkyl (1-6C) or a substituent selected from hydroxy and (1-6C) alkoxy; (iiiiii) A is R14, where R1 9 is Q4 where Q4 is cycloalkyl (3-7C), heyerocyclyl or alkyl (1-6C), and wherein any heyerocyclic group in a group R14 optionally bears one or more (for example 1, 2 or 3) substituents, which may be the same or different, selected of halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C) and alkoxy (1-6C), and wherein any group heterocyclyl in a group R14 optionally carries 1 or 2 substitutes fioxo or oxo, and wherein any group CH2 or CH3 in a group R14, other than a group CH2 in a heterocyclyl ring, optionally carries in each said group CH2 or CH3 one or more substitutes for halogen or alkyl (1-6C) or a substitute selected from hydroxy and (1-6C) alkoxy; (jjjjjj) A is Q4 wherein Q4 is a partially saturated or saturated 4, 5, 6 or 7 membered monocyclic heyerocyclic ring containing 1 nitrogen or oxygen heteroatom and optionally 1 additional heteroatom selected from oxygen, nitrogen and sulfur, and where Q4 optionally bears one or more (for example 1, 2 or 3) substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, hydroxy, amino, alkyl (1-6C), alkenyl (2-6C) ), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino, di- [(1-6C) alkyl] amino and alkanoyl (2-6C), alkanoyloxy (2-6C) and a group of the formula: -X6-R22 wherein X6 is a direct bond or is selected from O and N (R23), wherein R23 is hydrogen or alkyl (1-4C), and R22 is halo-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C) , amino-alkyl (1-4C), N-alkylamino (1-4C) -alkyl (1-4C), and N, N-di [alkyl] il (1-4C)] amino-alkyl (1-4C), and wherein Q4 optionally carries 1 or 2 oxo substituents; (kkkkkk) A is Q4 wherein Q4 is a monocyclic heterocyclic ring partially saturated with 5 or 6 membered salts conferring 1 heteroatom of nitrogen or oxygen heteroatom and optionally 1 additional heteroatom is selected from oxygen, nitrogen and sulfur, and wherein Q4 optionally carries one or more (for example 1, 2 or 3) substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, hydroxy, amino, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C) and alkoxy (1-6C), and wherein Q4 optionally bears 1 or 2 substituiofen oxo; (lily) A is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azeidinyl, pyrrolinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, homopiperidinyl, homopiperazinyl, dihydropyridinyl, tetrahydropyridinyl, dihydropyrimidinyl, teirahydropyrimidinyl, tetrahydrofuranyl and tetrahydropyranyl, and wherein A optionally bears one or more substitutes, which may be the same or differentiated, selected from fluoro, chloro, bromo, oxo, hydroxy, meily, ethyl, propyl, bufil, isopropyl, isobufil, frifluoromethyl, vinyl, isopropenyl, allyl, but-2-enyl, efinyl, 2-propynyl, butynyl, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethoxy, acetyl, propionyl, hydroxymethyl, methoxymethyl, ethoxymethyl, 2-hydroxyethyl, 2-methoxyethyl and 2-efoxy-yl; (mmmmmm) A is selected from cyclopropyl, pyrrolidinyl, piperazinyl, morpholinyl and fetrahydrofuranyl, and wherein A optionally bears one or more substituents, which may be the same or different, selected from methyl, ethyl, propyl, butyl, isopropyl and isobutyl (particularly methyl); (nnnnnn) A is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, homopiperidinyl, homopiperazinyl, tetrahydrofuranyl and tetrahydropyranyl, and wherein A optionally bears one or more substituents, which may be the same or different, is selected from fluoro, chloro , bromine, oxo, hydroxy, methyl, ethyl, propyl, propyl, trifluoromethyl, vinyl, allyl, eylinyl, 2-propynyl, methoxy, ethoxy, propoxy, isopropoxy, trifluoromethoxy and acetyl; (ooooo) A is selected from methyl, ethyl, propyl, isopropyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 1-hydroxypropyl, 2-hydroxypropyl, 2-hydroxyprop-2-yl, 1,3-dihydroxypropyl 2- (hydroxymethyl) prop-2-yl, 2-hydroxy-2-methylpropyl, methoxymethyl, 2-methoxy-yl, 1-methoxyethyl, 3-methoxypropyl, 1-methoxypropyl, 2-meioxypropyl, 2-mefoxiprop-2-yl, 2- (Mexoxymethyl) prop-2-yl, 2-meioxy-2-meph I, propyl, ethoxymethyl, 2-ethoxyethyl, 1-ethoxyethyl, 1-hydroxy-3-bromopropyl, (methylsulfonyl) methyl, aminomethyl, 2-amino-eyl, 1-amino-eyl, 3-aminopropyl, 1-aminopropyl, 2-aminopropyl, 2-aminoprop-2-yl, 2- (aminomethyl) prop-2-yl, JN-methylaminomethyl, 2- (JN-methylamino) eyl, 1- (JN-methylamino) ethyl, 3- (JN-methylamino) propyl, 1- (JN-mephilamino) propyl, 2- (N-meitylamino) propyl, 2- (JN- methylamino) prop-2-yl, 2- (JN-methylaminomeyl) prop-2-yl, [(N -methyl) - (N-tert-butoxycarbonyl) amino] methyl, 2- (JN-methylamino) -2-methylpropyl , JN. JN-di methyl ami nomethyl, 2- (JN, JN-dimethylamino) ethyl, 1 - (JN, JN-dimethylamino) yl, 3- (JN, J __- dimethylamino) propi, 1 - (JN, JN-dimethylamino) propyl, 2- (JN, JN-dimethylamino) propyl, 2- (JN, JN-dimethylamino) prop-2-yl, 2- (JN__N-dimethylaminometry) prop-2-yl, 2- (JN, JN-dimethylamino) -2-methylpropyl, methylamino, dimethylamino, erylamino, diethylamino, (2-chloroethyl) amino, methoxy, ethoxy, propoxy, butoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxycyclopropyl, 1-hydroxycyclobutyl, 1 - hydroxycyclooxyethyl, 1-hydroxycyclohexy, 1-hydroxymethyl clopropyl, 1-hydroxymethylcyclobutyl, 1-hydroxymethyl, cyclopentyl, 1-hydroxymethylcyclohexyl, tetrahydrofuran-2-yl, teirahydrofuran-3-yl, tefrahydropyran-2-yl, ephehydro-pyran-3-yl, tetrahydropyran-4-yl, azetidin- 2-yl, azetidin-3-yl, 1-methylazetidin-2-yl, 1-methylazetidin-3-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, 1-methylpyrrolidin-2-yl, 1-me ylpyrrolidin- 3-yl, pyrrolidin-1-ylmethyl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, 1-methylpiperidin-2-yl, 1-methyl-piperidin-3-yl, 1-methyl-piperidin-4- il, morpholin-4-yl, morpholin-4-ylmethyl, 1-methylpiperazin-4-ylmethyl; (pppppp) A is selected from methyl, ethyl, propyl, isopropyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 1-hydroxypropyl, 2-hydroxypropyl, 2-hydroxyprop-2-yl, 2- (hydroxymethyl) prop-2-yl, 2-hydroxy-2-methylpropyl, methoxymethyl, 2-methoxyethyl, 1-methoxy-ethyl, 3-methoxypropyl, 1-methoxypropyl, 2-methoxypropyl, 2-methoxyprop-2-yl, 2- (methoxymethyl) prop -2-yl, 2-methoxy-2-methylpropyl, ethoxymethyl, 2-ethoxyethyl, 1-ethoxyethyl, aminomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 1-aminopropyl, 2-aminopropyl, 2-aminoprop-2 -yl, 2- (aminomethyl) prop-2-yl, 2-amino-2-methylpropyl, JN-methylaminomethyl, 2- (jv? _-methylamino) ethyl, 1- (JN-meitylamino) efil, 3- (JN -methylamino) propyl, 1- (JN-methylamino) propyl, 2- (J_-meylamino) propyl, 2- (JN-methylamino) prop-2-yl, 2- (N-methylaminomethyl) prop-2-yl, 2- (N-methylamino) -2-methylpropyl, JN- N-dimethylaminomethyl, 2- (JN, N-dimethylamino) ethyl, 1- (JN, JN-dimethylamino) ethyl, 3- (JN, JN-dimethylamino) propyl , 1 - (JN, JN-dimethylamino) propiI, 2- (JN, JN-dimethylamino) propyl, 2- (Jl , JN-dimethylamino) prop-2-yl, 2- (J __., JN-dimethylaminometyl) prop-2-yl, 2- (jsL, JN-dimethylamino) -2-methylpropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1 -hydroxycyclopropyl, 1-hydroxycyclobutyl, 1-hydroxycyclopentyl, 1-hydroxycyclohexyl, 1-hydroxymethylcyclopropyl, 1-hydroxymethylcyclobutyl, 1-hydroxymethylcyclopentyl, 1-hydroxymethylcyclohexyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydropyran-2-yl , tetrahydropyran-3-yl, teirahydropyran-4-yl, azetidin-2-yl, azetidin-3-yl, 1-methylazephidin-2-yl, 1 -methylazeidin-3-yl, pyrrolidin-2-yl, pyrrolidin- 3-yl, 1-methylpyrrolidin-2-yl, 1-methyl pyrrolidin-3-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, 1-methyl-piperidin-2-yl and 1-methyl-piperidin -4-il; (aq) A is selected from methyl, ethyl, propyl, isopropyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 1-hydroxypropyl, 2-hydroxypropyl, 2-hydroxyprop-2-yl, 1,3-dihydroxypropyl 2- (hydroxymethyl) prop-2-yl, 2-hydroxy-2-mephylpropyl, methoxymethyl, 2-methoxyethyl, 1-methoxyethyl, 3-methoxypropyl, 1-methoxypropyl, 2-methoxypropyl, 2-methoxyprop-2-yl, 1-Hydroxy-3-bromopropyl, (methylsulfonyl) methyl, aminomethyl, 2-amino-eyl, 1-amino-eyl, 3-aminopropyl, 1-aminopropyl, 2-aminopropyl, 2-aminoprop-2-yl, 2- (aminomethyl) prop -2-yl, 2-amino-2-meitylpropyl, JN-methylaminomethyl, 2- (JN-methylamino) eile, 1 - (JN-meitylamino) efil, r (N-meityl) - (N-tert-butoxycarbonyl) amino ] methyl, JN.JN-d i met i aminomethyl, 2- (JN, JN-dimethylamino) ethyl, 1 - (JN, JN-dimethylamino) ethyl, methylamino, dimethylamino, yylamino, diethylamino, (2-chloroethyl) amino, meioxy, ethoxy, cyclopropyl, cyclobutyl, 1-hydroxycyclopropyl, 1-hydroxycyclobutyl, 1-hydroxymethylcyclopropyl, 1-hydroxymethylcyclobuyl , tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydropyran-2-yl, teirahydropyran-3-yl, tetrahydropyran-4-yl, pyrrolidin-2-yl, pyrroidin-3-yl, 1-methylpyrrolidin-2-yl , 1-methylpyrrolidin-3-yl, pyrrolidin-1-ylmethyl, morpholin-4-yl, morpholin-4-ylmethyl, 1-methyl-piperazin-4-ylmethyl; (rrrrrr) A is selected from methyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxy-yl, 3-hydroxypropyl, 1,3-dihydroxypropyl, 2- (hydroxymethyl) prop-2-yl, methoxymethyl, 1-methoxyethyl, 1-hydroxy- 3-bromopropil, (methylsulfonyl) methyl, aminomethyl, JN-melilaminomefil, [(N-methyl) - (N-tert-bufoxicarbonyl) amino] mephile, meilylamino, (2-chloro-eyl) amino, meioxy, 1-hydroxycyclopropyl, tetrahydrofuran-2-yl, 1-methylpyrrolidin-2-ii, pyrrolidin-1-methylmethyl, morpholin-4-ylmethi, 1-methylpiperazin-4-ylmefyl; (ssssss) A is selected from hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 1-hydroxypropyl, 2-hydroxypropyl, 2-hydroxyprop-2-yl, 2- (hydroxymethyl) prop-2-yl and 2- hydroxy-2-methylpropyl; (íítítít) A is selected from methyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl and 2-hydroxyprop-2-yl; (uuuuuu) A is selected from methyl and hydroxymethyl; (vvvvvv) A is hydroxymethyl; (wwwwww) A is a group of the formula Z- (CR 2R13) P-, where p is 1 or 2, each R12 and R13, which may be the same or different, is selected from hydrogen and alkyl (1 -3C) ), and wherein Z is a group of the formula NR16R17, wherein each of R16 and R17, which may be the same or different, is selected from hydrogen and alkyl (1-6C), and wherein any CH2 or CH3 in any of R12, R13 and Z, optionally carries in each said group CH2 or CH3 one or more (for example 1, 2 or 3) substituents of halogen or alkyl (1-6C), and wherein any CH2 or CH3 group in any of R12, R13 and Z that does not bind to a nitrogen atom optionally carries in each said CH2 or CH3 group a substiuyenyen selected from hydroxy and (1-6C) alkoxy; (xxxxxx) A is selected from aminomethyl, 2-aminoethyl, 1-aminopene, 3-aminopropyl, 1-aminopropyl, 2-aminopropyl, 2-aminoprop-2-yl, 2- (aminomethyl) prop-2-yl, 2- amino-2-methylpropyl, JN-meitylaminomethyl, 2- (JN-methylamino) ethyl, 1- (JN-methylamino) ethyl, 3- (JN-meitylamino) propyl, 1- (JN-methylamino) propyl, 2- (_N-methylamino) propyl, 2- (JN-methylamino) prop-2-yl, 2- (JN-methylaminomethyl) prop-2-yl, 2- (N-methylamino) -2-methylpropyl, JN.JN- dimethylaminomethyl, 2- (N, JN-dimethylamino) ethyl, 1- (Ji, JN-dimethylamino) ethyl, 3- (JN, JN-dimethylamino) propiI, 1 - (JN, JN-dimethylamino) propyl, 2- (JN , JN-dimethylamino) propyl, 2- (JN, _N-dimethylamino) prop-2-yl, 2- (JN, JN-dimethylaminomethyl) prop-2-yl, 2- (JN, J _.- dimethylamino) -2- methylpropyl and [(N-methyl) -N-tert-butoxycarbonyl) amino] methyl; and (yyyyyy) A is selected from aminomethyl, 2-aminoethyl, JN-meitylaminomethyl, 2- (N-methylamino) ethyl, N., J-.- dimethylaminometyl, 2- (JN, JN-dimethylamino) eyl and f (N-methyl) ) - (N-rt-butoxycarbonyl) amino] methyl (Parficularly A is JN, JN-dimethylaminometyl). A particular embodiment of the present invention is a quinazoline derivative of the formula I of the formula la: where: m is 0, 1 or 2; each R1, which may be the same or different, is selected from hydroxy, (1-6C) alkoxy, (3-7C) cycloalkyl, and (3-7C) cycloalkyl-alkoxy (1 -6C), and wherein any CH2 or CH3 group in a substitution R1 optionally carries in each said CH2 or CH3 group one or more halogen substituents or alkyl (1-6C), or a substituent selected from hydroxy and alkoxy ( 1-6C), R3a is selected from cyano, halogen, alkyl (1-4C), trifluoromethyl, alkoxy (1-4C), alkenyl (2-4C) and alkynyl (2-4C); n is 1 or 2; each R3b, which may be the same or different, is selected from cyano, halogen, alkyl (1-4C), trifluoromethyl, alkoxy (1-4C), alkenyl (2-4C) and alkynyl (2-4C) (particularly halogen) and alkyl (1-4C)); X1 is selected from O, S, SO, SO2, N (R7), CH (OR7), CON (R7), N (R7) CO, SO2N (R7), N (R7) SO2, OC (R7) 2, C (R7) 2O, SC (R7) 2, C (R7) 2S, CO, C (R7) 2N (R7) and N (R7) C (R7) 2, wherein each R7, which may be the same or different, it is hydrogen or alkyl (1-6C); Q1 is aryl, or heteroaryl, and wherein Q1 optionally bears one or more substituents (for example 1, 2 or 3), which may be the same or different, selected from halogen, cyano, nitro, hydroxy, amino, carboxy, carbamoyl , sulfamoyl, formyl, mercapto, alkyl (1-6C), alkenyl (2-8C), alkynyl (2-8C), alkoxy (1-6C), alkenyloxy (2-6C), alkynyloxy (2-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, alkoxycarbonyl (1-6C), N-alkylcarbamoyl (1-6C), N, JN-di- [(1-6C) alkyl] carbamoyl, (2-6C) alkanoyl, (3-6C) alkenoyl, (3-6C) alkynyloxy, -6C), alkanoylamino (2-6C), JN-alkyl (1 -6C) -alkylamino (2-6C), alkenoylamino (3-6C), JN-alkyl (1 -6C) -alkenoylamino (3-6C), alkynylamino (3-6C), JN-alkyl (1 -6C) -alkynylamino (3-6C), N-alkylsulfamoyl (1 -6C), N, JN-di- [alkyl (1-6C)] sulfamoyl, alkanesulfonylamino ( 1-6C), JN-alkyl (1-6C) -alkanesulfonylamino (1-6C) and a group of the formula: -X2-R8 wherein X2 is a direct bond or is selected from O, CO and N (R9) , wherein R9 is hydrogen or alkyl (1-6C), and R8 is halogen-alkyl (1-6C), hydroxy-alkyl (1-6C), carboxy-alkyl (1-6C), alkoxy (1-6C) -alkyl (1-6C), cyano-alkyl (1-6C), amino-alkyl (1-6C), JN-alkylamino (1-6C) -alkyl (1-6C), JN, f __- di [alkyl (1- 6C)] amino-alkyl (1-6C), alkanoylamino (2-6C) -alkyl (1-6C), N-alkyl (1-6C) -alkylamino (2-6C) -alkyl (1-6C), alkoxycarbonylamino (1-6C) -alkyl (1-6C), carbamoyl-alkyl (1-6C), N-alkylcarbamoyl (1-6C) -alkyl (1-6C), JN, JN-di [(1-6C) alkyl] carbamoyl-alkyl (1-6C), (1-6C) alkyl- (1-6C) alkyl ), alkylsulfinyl (1-6C) -alkyl (1-6C), alkylsulfonyl (1-6C) -alkylsulfamoyl (1-6C) alkyl (1-6C), N-alkylsulfamoyl (1-6C) alkyl (1-6C), N, J __- di-alkylsulfamoii (1 -6C) alquil (1-6C), (2-6C) alkanoyl-(1-6C) alkyl, (2-6C) alkanoyloxy (1-6C) or (1-6C) alkoxycarbonyl-(1-6C) alkyl, and wherein any CH2 or CH3 group in -X1-Q1 optionally carries in each said CH2 or CH3 group one or more (eg, 1, 2, or 3) halogen substitutes or (1-6C) alkyl or a subsitute selected from hydroxy, cyano, amino, (1-4C) alkoxy, (1-4C) alkylamino, and di- [(1-4C) alkylamino]]; R4, R4a, R5 and R5a, which may be the same or different, are selected from hydrogen and alkyl (1-6C), or R4 and R4a together with the carbon atom to which they are attached form a cycloalkyl ring (3- 7C), or R5 and R5a together with the carbon atom to which they are attached form a cycloalkyl (3-7C) ring, and wherein any CH2 or CH3 group in any of R4, R a, R5 and R5a optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) halogen substituents or a substituent selected from hydroxy, cyano, (1-6C) alkoxy, amino, (2-6C) alkanoyl, alkylamino (1-6C) and di- [alkylamino (1-6C)]; R6 is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C), cycloalkenyl ( 3-7C), cycloalkenyl (3-7C) -alkyl (1-6C), heterocyclyl and heterocyclyl-alkyl (1-6C), and wherein any heterocyclyl group in an optional R6 substituent carries one or more substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C) , alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, (2-6C) alkanoyl, alkanoyloxy ( 2-6C) and a group of the formula: -X3-R1 0 wherein X3 is a direct bond or is selected from O, CO, SO2 and N (R1 1), wherein R1 1 is hydrogen or alkyl (1 -4C), and R 0 is halogen-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino -alkyl (1 -4C), JN-alquila mino (1-4C) -alkyl (1-4C), and N, JN-di- [alkyl (1-4C)] amino-alkyl (1-4C), and wherein any heterocyclyl group in a substituent R6 optionally carries 1 or 2 oxo or thioxo substituents; and wherein any CH2 or CH3 group in a substituent R6, other than a CH2 group in a heterocyclyl group, optionally carries in each said CH2 or CH3 group one or more halogen substituents or alkyl (1-6C) or a substitute selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1 -6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, JN-alkylcarbamoyl (1-6C), J_J_, J_- di [alkyl (1-6C)] carbamoyl, alkanoyl (2-C) -6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), JN-alkyl (1 -6C) -alkanoylamino (2-6C), JN-alkylsulfamoyl (1 -6C), N, JN-di [alkyl (1-6C)] sulfamoyl, alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C); A is selected from hydrogen, a group of the formula Z- (CR12R13) P- and R14, wherein p is 1, 2, 3, or 4, each R12 and R13, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl (2-6C), or a group R12 and R13 attached to the same carbon atom form a ring of cycloalkyl (3-7C) or cycloalkenyl (3-) 7C), and wherein any CH2 or CH3 group in any of R12 and R3 optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) SUBSTITUTE SHEET Halogen or alkyl (1-6C) or a substituent selected from hydroxy, cyano, alkyl (1-6C), alkoxy (1-6C), amino, alkanoyl (2-6C), alkylamino ( -6C) and di- [alkyl (1 -6C)] amino, Z is selected from hydrogen, OR15, NR16R17, alkylsulfonyl (1-6C), alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C), wherein each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C) and alkoxycarbonyl (1-6C), or Z is a group of the formula: Q2-X4-wherein X4 is selected from O, N (R18), SO2, and SO2N (R18), wherein R18 is hydrogen or alkyl (1) -6C), and Q2 is cycloalkyl (3-7C), cycloalkenyl (3-7C) or heterocyclyl, R14 is selected from hydrogen, OR19 and NR16R17, wherein R1 9 is selected from alkyl (1-6C), alkenyl (2) -6C) and alkynyl (2-6C), and wherein R16 and R17 are as defined above, or R14 is a group of the formula: Q3-X5-wherein X5 is selected from O and N (R20), wherein R20 is hydrogen or alkyl (1-6C), and Q3 is cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C), cycloalkenyl (3-7C), cycloalkenyl ( 3-7C) -alkyl (1-6C), heterocyclyl and heterocyclyl-alkyl (1-6C), or R14 is Q4 wherein Q4 is cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1 -6C), cycloalkenyl (3-7C), cycloalkenyl (3-7C) -alkyl (1 -6C), heterocyclyl or heterocyclyl-alkyl (1-6C), and wherein adjacent carbon atoms in any alkylene chain (2-6C) in a substituent Z or R14 are optionally separated by the insertion in the chain of a selected group of O, S, SO, SO2, N (R21), CO, -C = C and -C = C- , wherein R21 is hydrogen or alkyl (1-6C), and wherein any heterocyclyl group in a substrate Z or R14 optionally carries one or more (eg, 1, 2 or 3) substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1- 6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(C 1-6C)] amino, alkanoyl (2-6C), alkanoyloxy (2-6C) and of a group of the formula: -X6-R22 wherein X6 is a direct bond or is selected from O, CO, SO2 and N (R23), wherein R23 is hydrogen or (1-4C) alkyl, and R22 is halo-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-) 4C), amino (1-4C) alkyl, N-alkylamino (1-4C) -alkyl (1-4C), and N, N-di.alkyl (1-4C)] amino-alkyI (1 -4C), and wherein any heterocyclyl group in a Z or R14 substituent optionally carries 1 or 2 oxo or thioxo substituents, and wherein any CH2 or CH3 group in a Z or R14 group, other than a CH2 group in a ring of heterocyclyl, optionally carries in each said group CH2 or CH3 one or more substituents of halogen or alkyl (1-6C) or a substituent selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl ( 2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [alkyl (1-6C)] amino, JN-alkylcarbamoyl (1-6C), JN, J __- d¡ [alkyl (1-6C)] carbamoyl, alkanoyl (2-6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), JN- alkyl (1-6C) -alkylamino (2-6C), JN-alkylsul famoyl (1-6C), N, N-di [alkyl (1-6C)] sulfamoyl, alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C); or a pharmaceutically acceptable salt thereof. Another embodiment of the present invention is a quinazoline derivative of the formula la, wherein; m is 0 or 1; R1 is selected from (1-4C) alkoxy (for example methoxy or ethoxy), and wherein any CH2 or CH3 group in a substituent R1 optionally carries in each said CH2 or CH3 group one or more fluoro or chloro substituents, or a substituent selected from hydroxy and (1-3C) alkoxy; R3a is selected from hydrogen, halogen, trifluoromethyl, alkyl (1-4C), alkoxy (1-4C), alkenyl (2-4C) and alkynyl (2-4C); n is 1 or 2; each R3b, which may be the same or different, is selected from halogen and alkyl (1-4C); X1 is selected from O, S and OC (R7) 2, wherein each R7, which may be the same or different, is hydrogen or alkyl (1-6C); Q1 is aryl, or heteroaryl, and wherein Q1 optionally bears one or more substituents (for example 1, 2 or 3), which may be the same or different, selected from halogen, cyano, nitro, hydroxy, amino, carboxy, carbamoyl , sulfamoyl, formyl, mercapto, alkyl (1-6C), alkenyl (2-8C), alkynyl (2-8C), alkoxy (1-6C), alkenyloxy (2-6C), alkynyloxy (2-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, alkoxycarbonyl (1-6C), JN-alkylcarbamoyl ( 1 -6C), JN, N-di- [(1-6C) alkyl] carbamoyl, (2-6C) alkanoyl, (3-6C) alkenoyl, (3-6C) alkynyl, (2-6C) alkanoyloxy, alkanoylamino (2-6C), JN-alkyl (1-6C) -alkylamino (2-6C), alkenoylamino (3-6C), JN-alkyl (1-6C) -alkenoylamino (3-6C), alkynylamino (3-6C) ), JN-alkyl (1-6C) -alkynylamino (3-6C), N-alkylsulfamoyl (1-6C), JN, JN-di- [alkyl (1-6C)] sulfamoyl, alkanesulfonylamino (1-6C), JN-alkyl (1-6C) -alkanesulfonylamino (1-6C) and a group of the formula: -X2-R8 e n where X2 is a direct bond or is selected from O, CO and N (R9), where R9 is hydrogen or alkyl (1-6C), and R8 is halogen-alkyl (1-6C), hydroxy-alkyl (1-6C), carboxy-alkyl (1-6C), alkoxy (1-6C) -alkyl (1-6C), cyano-alkyl (1) -6C), amino-alkyl (1-6C), N-alkylamino (1-6C) -alkyl (1-6C), JN, JN-di [(1-6C) alkyl] amino-alkyl (1-6C) , alkanoylamino (2-6C) -alkyl (1-6C), N-alkyl (1-6C) -alkylamino (2-6C) -alkyl (1-6C), alkoxycarbonylamino (1-6C) -alkyl (1-6C) ), carbamoyl-alkyl (1-6C), JN-alkylcarbamoyl (1-6C) -alkyl (1-6C), JN, JN-di [(1-6C) alkyl] carbamoyl-alkyl (1-6C), alkylthio (1-6C) -alkyl (1-6C), alkylsulfinyl (1-6C) -alkyl (1-6C), alkylsulfonyl (1-6C) -alkylsulfamoyl (1-6C) alkyl (1-6C), N-alkylsulfamoyl (1-6C) alkyl (1-6C), N, N-di-alkylsulfamoyl (1-6C) alkyl (1-6C), alkanoy (2-6C) -alkyl (1-6C), alkanoyloxy (2-6C) ) -alkyl (1-6C) or alkoxycarbonyl (1-6C) -alkyl (1-6C), and wherein any CH2 or CH3 group in -X1-Q1 optionally carries in each said CH2 or CH3 group one or more (by Example 1, 2, or 3) Substituents of halogen or alkyl (1-6C) or a substituent selected of hydroxy, cyano, amino, alkoxy (1-4C), alkylamino (1-4C) and di- [alkylamino (1-4C)]; R4, R4a, R5 and R5a, which may be the same or different, are selected from hydrogen and alkyl (1-6C), or R4 and R4a together with the carbon atom to which they are attached form a cycloalkyl ring (3- 7C), or R5 and R5a together with the carbon atom to which they are attached form a cycloalkyl (3-7C) ring, and wherein any CH2 or CH3 group in any of R4, R4a, R5 and R5a optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) subsfidients of halogen or a subsystem selected from hydroxy, cyano, (1-6C) alkoxy, amino, alkanoyl (2-6C), alkylamino (1-6C) and di- [alkylamino (1-6C)]; R6 is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C), heterocyclyl and heterocyclyl-alkyl (1-6C), and wherein any heterocyclyl group in a substituent R6 optionally carries one or more substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C) , alkylamino (1-6C), di- [(1-6C) alkyl] amino, (2-6C) alkanoyl, (2-6C) alkanoyloxy and a group of the formula: wherein X3 is a direct bond or select from O, CO, SO2 and N (R1 1), wherein R1 1 is hydrogen or alkyl (1-4C), and R10 is halo-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl ( 1 -4C), cyanoalkyl (1-4C), amino-alkyl (1-4C), JN-alkylamino (1-4C) -alkyl (1-4C), and N, N-di- [alkyl (1 -4C)] amino-alkyl (1-4C), and wherein any heterocyclyl group in a substituent R6 optionally carries 1 or 2 oxo or thioxo substituents; and wherein any CH2 or CH3 group in a R6 substituent, differentiates a CH2 group in a hemerocyclyl group, optionally carries in each said CH2 or CH3 group one or more halogen substituents or alkyl (1-6C) or a substituent selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1 -6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, JN-alkylcarbamoyl (1-6C), JN, N-di [(1-6C) alkyl] carbamoyl, alkanoyl (2C). -6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), N-alkyl (1 -6C) -alkanoyamino (2-6C), JN-alkylsulfamoyl (1 -6C), N, N-di [alkyl (1 -6C)] sulfamoyl, alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C); A is selected from a group of the formula Z- (CR12R13) P- and R14, wherein p is 1, 2 or 3, each R12 and R13, which may be the same or different, is selected from hydrogen, alkyl (1) -6C), alkenyl (2-6C) and alkynyl (2-6C), or a group R12 and R13 attached to the same carbon atom form a cycloalkyl ring (3-7C), and wherein any CH2 or CH3 group in any of R12 and R13 optionally carries in each said group CH2 or CH3 one or more (for example 1, 2 or 3) substituents of halogen or alkyl (1-6C) or a substituent selected from hydroxy, cyano, alkyl (1-6C) ), (1-6C) alkoxy, amino, (2-6C) alkanoyl, (1-6C) alkylamino and di- [(1-6C) alkyl] amino, Z is selected from hydrogen, OR15, NR16R17 and R14 where each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl (2-6C), R14 is a monocyclic heterocyclic ring partially saíurado or saíurado of 4, 5, 6 or 7 members containing 1 heter Oxygen of nitrogen or oxygen and optionally 1 additional heteroalomene selected from oxygen, niorogen and sulfur, and wherein any heterocyclic group in a sub-residue R14 optionally carries one or more (for example 1, 2 or 3) subsitutes, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio ( 1 -6C), alkylsulfinyl (1 -6C), alkylsulfonyl (1 -6C), alkylamino, di- [(1-6C) alkyl] amino, (2-6C) alkanoyl, (2-6C) alkanoyloxy and a group of the formula: -X6-R22 wherein X6 is a direct bond or is selected of O, CO, SO2 and N (R23), wherein R23 is hydrogen or alkyl (1-4C), and R22 is halogen-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C), 4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C), JN-alkylamino (1-4C) -alkyl (1-4C), and JN, JN-di [alkyl (1-4C)] amino-alkyl (1-4C), and wherein any heterocyclyl group in an R 14 substituent optionally carries 1 or 2 oxo or ioxo substityes, and wherein any CH2 or CH3 group in a Z group optionally carries in each said group CH2 or CH3 one or more substituents of halogen or alkyl (1-6C) or a substituent selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2- 6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, JN-alqu ilcarbamoyl (1 -6C), N, J __- di [alk (1 -6C)] carbamoyl, alkanoyl (2-6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), JN-alkyl (1 -6C) -alkanoylamino (2-6C), N-alkylsulfamoyl (1 -6C), N, N-di [(1-6C) alkyl] sulfamoyl, alkanesulfonylamino (1-6C) and N.-alkyl (1-6C) ) -alkanesulfonylamino (1 -6C); or a pharmaceutically acceptable salt thereof. In one embodiment, in the compound of the formula, m is 0 or m is 1 and R 1 is (1-3C) alkoxy, for example methoxy. Particularly m is 0. In another embodiment, in the compound of the formula la, n is 0 and R3a is selected from halogen, trifluoromethyl, alkyl (1-4C), alkoxy (1-4C), alkenyl (2-4C) and alkynyl (2-4C). Particularly R3a is selected from halogen and alkyl (1 -3C), more particularly R3a is selected from chlorine and methyl, even more particularly R3a is chlorine. In this mode n is properly 0 or 1. Particularly n is 0. In another embodiment, in the compound of formula la, X1 is selected from O, S and OC (R7) 2, wherein R7 is hydrogen or alkyl (1 -3C), more particularly X1 is selected from O and OC (R7) 2 for example X1 is selected from O, OCH2 and OC (CH3) 2. In another embodiment, in the compound of the formula la, X1 is selected from S and OC (R7) 2, wherein R7 is hydrogen or alkyl (1 -3C), more particularly X1 is OC (R7) 2, for example X1 is OCH2. In another embodiment, in the compound of the formula la, Q1 is selected from phenyl and a 5- or 6-membered monocyclic heteroaryl ring, such ring contains 1 nitrogen heteroatom and optionally 1 additional hetero-atom is selected from oxygen, nitrogen and sulfur, and wherein Q1 optionally bears one or more substituents (for example 1, 2 or 3), which may be the same or different, selected from halogen, hydroxy, cyano, carboxy, nitro, amino, alkyl (1-4C), alkoxy ( 1 -4C), alkenyl (2-4C), alkynyl (2-4C), alkylthio (1-4C), alkylsulfinyl (1-4C), alkylsulfonyl (1-4C), alkanoyl (2-4C), JN-alkylamino (1 -4C), JN, JN-di [alkyl (1-4C)] amino, alkoxycarbonyl (1-4C), carbamoyl, JN-alkylcarbamoyl (1-4C), JN, J __- di- [alkyl (1 - 4C)] carbamoyl, alkanoyloxy (2-4C), alkanoylamino (2-4C), JN-alkyl (1-4C) -alkylamino (2-4C), halogen-alkyl (1-4C), hydroxy-alkyl (1 - 4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), carboxy-alkyl (1-4C), amino-alkyl (1-4C) ), JN-alkylamino (1-4C) -alkyl (1-4C) and JN, JN-di- [alkyl (1-4C)] amino-alkyl (1-4C) In another embodiment, in the compound of the formula la, Q1 is selected from phenyl, pyridyl, pyrazinyl, thiazolyl and isoxazolyl, optionally substiuted by 1, 2, or 3 sublifuges, which may be the same or different, selected from halogen (for example fluoro or chloro), hydroxy, alkyl ( 1 -4C) and alkoxy (1-4C). For example Q1 is selected from phenyl optionally subsfifuged with 1 or 2 substituents selected from fluoro and chloro or Q1 is selected from 2-pyridyl, 3-pyridyl, 2-pyrazinyl, 1,3-thiazol-2-yl, 1, 3- thiazol-4-yl, 1,3-thiazol-5-yl and isoxazol-3-yl (particularly 2-pyridyl, 3-pyridyl, 2-pyrazinyl, 1,3-thiazol-2-yl, 1,3-thiazole -4-yl and isoxazol-3-yl), and wherein any heterocyclic group in Q1 optionally carries 1, 2, or 3 substituents, which may be the same or different, selected from halogen (for example fluoro or chloro), hydroxy , alkyl (1-4C) and alkoxy (1-4C). In another embodiment, in the compound of the formula la, Q1 is pyridyl (for example 2-pyridyl or 3-pyridyl, particularly 2-pyridyl), which optionally carries 1, 2, or 3 sub-bases, which may be the same or different , selected from halogen (for example fluoro or chloro), hydroxy, alkyl (1-4C) and alkoxy (1-4C). For example, Q1 is particularly pyridyl, optionally substituted by 1 or 2 substituents of (1-4C) alkyl (for example by 1 or 2 substituents of methyl). In another embodiment, in the compound of the formula la, R4, R4a, R5 and R5a are selected from hydrogen and alkyl (1 -3C), for example R4, R4a, R5 and R5a are selected from hydrogen and methyl. In another mode, in the compound of the formula la, R4, R4a, R5 and R5a are all hydrogen. In another embodiment, in the compound of the formula la, R 4, R 5 and R 5a are all hydrogen and R 4 is alkyl (1 -3C), for example methyl. In another embodiment, in the compound of the formula la, R4, R5 and R5a are all hydrogen and R5 is (1 -3C) alkyl, for example, meily.

In another embodiment, in the compound of the formula la, R4 and R4a are both hydrogen and R5 and R5a are both (1 -3C) alkyl, for example methyl. In another embodiment, in the compound of the formula la, R6 is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalkyl (3- 7C) -alkyl (1-6C), heterocyclyl, and heterocyclyl-alkyl (1-6C), wherein any heterocyclyl group in R6 is a 4, 5, 6, or 7-member partially saturated or saturated monocyclic heterocyclyl ring containing 1 or 2 heteroatoms selected from oxygen, nitrogen and sulfur, and wherein any heterocyclyl group in a substituent R6 optionally bears one or more substituents, which may be the same or different, selected from halogen, trifluoromethyl, hydroxy, amino, alkyl (1-6C) ), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylamino (1 -6c), di- [(1-6C) alkyl] amino, (2-6C) alkanoyl, and of a group of the formula: -X3-R10 wherein X3 is a direct bond or is selected from O and N (R1 1), wherein R1 is hydrogen or alkyl (1-4C), and R10 is halogen-alkyl (1-4C), hydroxy-alkyl (1 - 4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C), N-alkylamino (1-4C) -alkyl (1-4C) , and JN, N-di- [alkyl (1-4C)] amino-alkyl (1-4C), and wherein any heterocyclyl group in a SUBSTITUTE R6 optionally carries 1 or 2 oxo substituys.

In another embodiment, in the compound of the formula la, R 6 is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-4C), heterocyclyl and heterocyclyl -alkyl (1-4C), wherein any heterocyclic group in R6 is a 4, 5, 6 or 7 member partially saturated or monocyclic heterocyclyl ring containing 1 or 2 heteroatoms selected from oxygen, nitrogen and sulfur, and wherein any heyerocyclic group in a substituent R 6 optionally carries one or more substituents, which may be the same or different, selected from fluoro, chloro, bromo, hydroxy, alkyl (1-4C), alkenyl (2-4C), alkynyl (2-4C) and alkoxy (1 - 4C), and where any heterocyclic group in a subscript R 6 optionally carries 1 oxo substituent, and wherein any CH2 or CH3 group on a substituent R6, other than a CH2 group on a heterocyclyl ring, optionally carries in each said CH2 or CH3 group one or more substituents selected from fluoro and chloro, or a substituent selected from hydroxy and (1-4C) alkoxy, alkylamino (1-6C) and di- [(1-6C) alkyl] amino. In another embodiment, in the compound of the formula la, R 6 it is selected from hydrogen and alkyl (1-4C). For example R6 is alkyl (1 -3C) such as methyl. In another embodiment, in the compound of the formula la, R 6 is selected from hydrogen, methyl, ethyl, 2-hydroxyethyl, 2-methoxyethyl, propyl, isopropyl, allyl, 2-propynyl, cyclopropyl, cyclobutyl, piperidinyl, tetrahydropyranyl and cyclopropylmethyl, and wherein any CH2 group in a cycloalkyl group in R6 optionally it carries in each group CH2 1 or 2 substituents selected from hydroxy, meily, ethyl, methoxy and ethoxy, and wherein any heterocyclyl group in R6 optionally bears one or more substituents, which may be the same or different, is selected from fluoro, chloro , bromine, oxo, hydroxy, methyl, ethyl, propyl, is'opropyl, trifluoromethyl, methoxy, ethoxy, propoxy, isopropoxy and trifluoromethoxy. In another embodiment, in the compound of the formula la, A is a group of the formula Z- (CR12R13) P-, where p is 1 or 2, each R12 and R13, which may be the same or different, is selected of hydrogen and alkyl (1-4C), or a group R12 and R13 attached to the same carbon atom form a cycloalkyl ring (3-6C), and wherein any CH2 or CH3 group in any of R12 and R13, optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) substituents of halogen or alkyl (1-4C) or a subsitute selected from hydroxy and (1-4C) alkoxy, and wherein Z is selected from hydrogen, OR 5, NR16R17 and alkylsulfonyl (1-6C), wherein each of R15, R16 and R17, which may be the same or different , it is selected from hydrogen, alkyl (1-4C) and alkoxycarbonyl (1-4C). For example, in one embodiment, Z is selected from hydrogen, hydroxy, methoxy, N-methylamino, N, N-dimethylamino, (N-methyl) - (N-tert-butoxycarbonyl) amino and methylsulfonyl (particularly Z is hydroxy). In another modality, in the compound of the formula la, A is a group of the formula Z- (CR12R13) P-, where p is 1 or 2, each R12 and R13, which may be the same or different, is selected of hydrogen and alkyl (1-4C), or a group R12 and R13 attached to the same carbon atom form a cycloalkyl ring (3-6C), and wherein any CH2 or CH3 group in any of R12 and R13, optionally bears in each said group CH2 or CH3 one or more (for example 1, 2 or 3) substituents of halogen or alkyl (1-4C) or a substituent selected from hydroxy and alkoxy (1-4C), and wherein Z is selected from hydrogen, hydroxy and alkoxy (1 -3C). For example Z is hydrogen or hydroxy, particularly Z is hydroxy. In another embodiment, in the compound of the formula la, A is selected from methyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl and 2-hydroxyprop-2-yl. Particularly A is hydroxymethyl. In another embodiment, in the compound of the formula the: m is 0; R3a is selected from fluoro, chloro and alkyl (1 -3C) (for example R3a is chloro or methyl, particularly R3a is chloro); n is 0; X1 is selected from O and OCH2 (for example, X1 is OCH2); R4, R4a, R5, R5a are selected from hydrogen and alkyl (1 -3C), for example R4, R4a, R5, R5a is selected from hydrogen and meityl (for example R4a and R5a are hydrogen and one of R4 and R5 is methyl) and the ear of R4 and R5 is hydrogen or R4 and R4a are both hydrogen and R5 and R5a, both are mephyl); or R4 and R4a june with the carbon atom to which they are attached form cycloalkyl ring (3-6C), or R5 and R5a together with the carbon atom to which they are attached form cycloalkyl ring (3-6C); R6 is hydrogen or alkyl (1 -3C), for example R6 is hydrogen or methyl (a particular value for R6 is methyl); A is a group of the formula Z- (CR12R1 3) P-, where p is 1 or 2, each R12 and R13, which may be the same or different, is selected from hydrogen and alkyl (1 -3C), or a group R12 and R13 linked to the same carbon atom form a cycloalkyl ring (3-6C), and wherein Z is selected from hydrogen, hydroxy and (1-3C) alkoxy (for example Z is hydrogen or hydroxy, particularly Z it is hydroxy). In another embodiment, in the compound of the formula la: m is 0; R3a is selected from fluoro, chloro and alkyl (1 -3C) (for example R3a is chloro or methyl, particularly R3a is chloro); n is 0; X1 is selected from O, OCH2 and OC (CH3) 2 (for example X1 is OCH2); R4, R4a, R5, R5a are selected from hydrogen and alkyl (1 -3C), for example R4, R4a, R5, R5a is selected from hydrogen and meityl (for example, R4, R4a, R5, R5a are hydrogen ions, or R4a and R5a are hydrogen and one of R4 and R5 is methyl and the other of R4 and R5 is hydrogen or R4 and R4a are both hydrogen and R5 and R5a are both methyl); or R6 is selected from hydrogen, alkyl (1 -3C), alkenyl (2-3C), alkynyl (2-3C), cycloalkyl (3-5C), cycloalkyl (3-5C) -alkyl (1 -3C) and heterocyclyl , and wherein any heterocyclyl group in a substituent R6 optionally bears one or more substituents of (1-6C) alkyl (for example R6 is hydrogen or methyl (a particular value for R6 is methyl)); A is selected from a group of the formula Z- (CR12R13) P-, where p is 1 or 2, each R12 and R13, which may be the same or different, is selected from hydrogen and alkyl (1-6C), and wherein any CH2 or CH3 group in any of R12 and R13, optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) halogen substituents or a selected substitution of hydroxy and alkoxy (1-) 6C) (particularly hydroxy), Z is selected from hydrogen, OR15, NR16R17 and alkylsulfonyl (1-6C), wherein each of R15, R16 and R17 which may be the same or different, is selected from hydrogen, alkyl ( 1-6C) and alkoxycarbonyl (1-6C), R14 is selected from OR19 and NR16R17, wherein R19 is selected from alkyl (1-6C) and wherein R16 and R17 are as defined above, or R14 is Q4 in wherein Q4 is cycloalkyl (3-7C), heterocyclyl or heterocyclyl-alkyl (1-6C), and wherein any heterocyclyl group in a substituent Z or R 14 optionally carries one or more (for example 1, 2 or 3) substituents, which may be the same or different, selected from halogen, hydroxy, alkyl (1-6C) and alkoxy (1-6C) (particularly alkyl (1-6C)), and wherein any CH2 group or CH3 in a group Z or R14, different from a group CH2 in a heterocyclyl ring, optionally carries in each said group CH2 or CH3 one or more substitutents of halogen or alkyl (1-6C) or a substituent selected from hydroxy and alkoxy ( 1-6C) (particularly a substituent selected from halogen and hydroxy). Another particular embodiment of the present invention is a quinazoline derivative of the formula I of the formula I b: Ib wherein: R3a is selected from cyano, halogen, alkyl (1-4C), trifluoromethyl, alkoxy (1-4C), alkenyl (2-4C) and alkynyl (2-4C); Q1 is aryl, or heteroaryl, and wherein Q1 optionally bears one or more substituents (for example 1, 2 or 3), which may be the same or different, selected from halogen, cyano, nitro, hydroxy, amino, carboxy, carbamoyl , sulfamoyl, formyl, mercapto, alkyl (1-6C), alkenyl (2-8C), alkynyl (2-8C), alkoxy (1-6C), alkenyloxy (2-6C), alkynyloxy (2-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [alkyl (1- 6C)] amino, alkoxycarbonyl (1-6C), JN-alkylcarbamoyl (1-6C), N, N-di- [(1-6C) alkyl] carbamoyl, (2-6C) alkanoyl, alkenoyl (3-6C) , alkynyl (3-6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), JN-alkyl (1-6C) -alkanoylamino (2-6C), alkenoylamino (3-6C), N-alkyl ( 1-6C) -alkenoylamino (3-6C), alkynylamino (3-6C), JN-alkyl (1-6C) -alkynylamino (3-6C), JN-alkylsulfamoyl (1-6C), JN, JN-di- [alkyl (1-6C)] sulfamoyl, alkanesulfonylamino (1-6C), N-alkyl (1-6C) -alkanesulfonylamino (1-6C) and a group of the formula: -X2-R8 wherein X2 is a direct bond or is selected from O, CO and N (R9), wherein R9 is hydrogen or alkyl (1-6C), and R8 is halogen-alkyl (1-6C), hydroxy-alkyl (1-6C), carboxy-alkyl (1-6C), (1-6C) alkoxy- (1-6C) alkyl, (1-6C) cyanoalkyl, (1-6C) amino-, JN-alkylamino (1-6C) -alkyl (1) -6C), JN, N-di [alkyl (1-6C)] amino-alkyl (1-6C), alkanoylamino (2-6C) -alkyl (1-6C), N-alkyl (1-6C) -alkylamino (2-6C) -alkyl (1-6C), alkoxycarbonylamino (1-6C) - alkyl (1-6C), carbamoyl-alkyl (1-6C), N-alkylcarbamoyl (1-6C) -alkyl (1-6C), N, JN-di [(1-6C) alkyl] carbamoyl-alkyl (1 -6C), alkylthio (1-6C) -alkyl (1-6C), alkylsulfinyl (1-6C) -alkyl (1-6C), alkylsulfonyl (1-6C) -alkylsulfamoyl (1-6C) alkyl (1-6C) ), JN-alkylsulfamoyl (1-6C) alkyl (1-6C), N, N-di-alkylsulfamoyl (1-6C) alkyl (1-6C), alkanoyl (2-6C) -alkyl (1-6C), alkanoyloxy (2-6C) -alkyl (1-6C) or alkoxycarbonyl (1-6C) -alkyl (1-6C), and wherein any group CH2 or CH3 in -X1-Q1 optionally carries in each said group CH2 or CH3 one or more (for example 1, 2, or 3) substituents of halogen or alkyl (1-6C) or a substiuent selected from hydroxy, cyano, amino, alkoxy (1-4C), alkylamino (1-4C) and di- [alkylamino (1-4C)]; R4, R4a, R5 and R5a, which may be the same or different, are selected from hydrogen and alkyl (1-6C), and wherein any CH2 or CH3 group in any of R4, R4a, R5 and R5a optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) halogen substituents or a substituent selected from hydroxy, cyano, (1-6C) alkoxy, amino, (2-6C) alkanoyl, alkylamino (1-6C) ) and di- [alkylamino (1 -6C)]; R6 is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C), cycloalkenyl ( 3-7C), cycloalkenyl (3-7C) -alkyl (1-6C), heterocyclyl and heterocyclyl-alkyl (1-6C), and wherein any heterocyclyl group in a substituent R6 optionally carries one or more substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C) , alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, (2-6C) alkanoyl, alkanoyloxy ( 2-6C) and a group of the formula: -X3-R10 wherein X3 is a direct bond or is selected from O, CO, SO2 and N (R11), wherein R11 is hydrogen or alkyl (1-4C) , and R10 is halo (1-4C) alkyl, hydroxy (1-4C) alkyl, (1-4C) alkoxy- (1-4C) alkyl, cyano (1-4C) alkyl, amino-alkyl (1) -4C), N-alkylamino (1-4C) - alkyI (1-4C), and N, JN-di- [alkyl (1-4C)] amino-alkyl (1-4C), and wherein any heterocyclyl group in a substituent R6 optionally carries 1 or 2 sub-oxi or thioxo subsides; and wherein any CH2 or CH3 group in a substituent R6, other than a CH2 group in a heterocyclyl group, optionally carries in each said CH2 or CH3 group one or more halogen substituents or (1-6C) alkyl or a substifuge selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkyl (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1 -6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, JN-alkylcarbamoyl (1-6C), JN, N.-di [(1-6C) alkyl] carbamoyl, alkanoyl ( 2-6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), JN-alkyl (1-6C) -alkylamino (2-6C), JN-alkylsulfamoyl (1-6C), JN, JN-di [ alkyl (1-6C)] sulfamoyl, alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C); A is selected from hydrogen, a group of the formula Z- (CR12R13) P- and R14, wherein p is 1, 2, 3, or 4, each R12 and R13, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl (2-6C), or a group R12 and R13 attached to the same carbon atom form a ring of cycloalkyl (3-7C) or cycloalkenyl (3-) 7C), and wherein any CH2 or CH3 group in any of R12 and R13 optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) halogen substituents or alkyl (1-6C) or a substituent selected from hydroxy, cyano, alkyl (1-6C), alkoxy (1-6C), amino, alkanoyl (2-6C), alkylamino (1-6C) and di- [alkyl (1-6C)] amino, Z is selected from hydrogen, OR15, NR16R17, alkylsulfonyl (1-6C), alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C), wherein each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl ( 2-6C) and alkoxycarbonyl (1-6C), or Z is a group of the formula: Q2-X4- wherein X4 is selected from O, N (R1 8), SO2 and SO2N (R1 8), wherein R1 8 is hydrogen or alkyl (1-6C), and Q2 is cycloalkyl (3-7C), cycloalkenyl (3-7C) or heterocyclyl, R14 is selected from hydrogen, OR19 and NR16R17, wherein R19 is selected from alkyl (1) -6C), alkenyl (2-6C) and alkynyl (2-6C), and wherein R16 and R17 are as defined above, or R14 is a group of the formula: Q3-X5-wherein X5 is selected from O and N (R20), wherein R20 is hydrogen or alkyl (1-6C), and Q3 is cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C), cycloalkenyl (3-7C), Cycloalkenyl (3-7C) -alkyl (1-6C), heterocyclyl and heterocyclyl-alkyl (1-6C), or R14 is Q4 wherein Q4 is cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C), cycloalkenyl (3-7C), cycloalkenyl ( 3-7C) -alkyl (1-6C), heterocyclic or heterocyclyl-alkyl (1-6C), and wherein adjacent carbon atoms in any (2-6C) alkylene chain in a Z or R14 substituent are optionally separated by the insertion in the chain of a selected group of O, S, SO, SO2, N (R21), CO, -C = C and -C = C-, wherein R21 is hydrogen or alkyl (1-6C), and wherein any heterocyclyl group in a substitutent Z or R14 optionally bears one or more (for example 1, 2 or 3) subsides, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl , mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C) ), alkylamino (1-6C), di- [(1-6C) alkyl] amino, (2-6C) alkanoyl, (2-6C) alkanoyloxy and e is a group of the formula: -X6-R22 wherein X6 is a direct bond or is selected from O, CO, SO2 and N (R23), wherein R23 is hydrogen or alkyl (1-4C), and R22 is halogen -alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C), JN -alkylamino (1-4C) -alkyl (1-4C), and JN, N-di [(1-4C) alkyl] amino-alkyl (1-4C), and wherein any heterocyclyl group in a substituent Z or R14 optionally it carries 1 or 2 substitutes oxo or thioxo, and where any group CH2 or CH3 in a group Z or R14, different to a group CH2 in a heterocyclyl ring, optionally carries in each said group CH2 or CH3 one or more substituents of halogen or alkyl (1-6C) or a substituent selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-) 6C), alkylsulfinyl (1 -6C), alkylsulfonyl (1 -6C), alkylamino (1 -6C), di- [alkyl (1 -6C)] amino, JN-alkylcarbamoyl (1 -6C), N, N-di [(1-6C) alkyl] carbamoyl, (2-6C) alkanoyl, (2-6C) alkanoyloxy, (2-6C) alkanoylamino, (1-6C) JN-alkyl (2-6C) alkylamino ), JN-alkylsulfamoyl (1 -6C), JN, JN-di [alky (1 -6C)] sulfamoyl, alkanesulfonylamino (1 -6C) and JN-alkyl (1 -6C) -alkanesulfonylamino (1 -6C); or a pharmaceutically acceptable salt thereof. Another particular embodiment of the present invention is a quinazoline derivative of the formula I of the formula Ib wherein: R 3a is selected from hydrogen, fluoro, chloro, trifluoromethyl, alkyl (1 -3C), alkoxy (1 -3C), alkenyl (2-4C) and alkynyl (2-4C); Q1 is selected from phenyl, pyridyl, pyrazinyl, thiazolyl and isoxazolyl, optionally substituted by 1, 2, or 3 substituents, which may be the same or different, selected from halogen (for example fluoro or chloro), hydroxy, alkyl (1 - 4C) and alkoxy (1-4C); R4, R4a, R5 and R5a, which may be the same or different, are selected from hydrogen and alkyl (1 -3C), and wherein any CH2 or CH3 group in any of R4, R4a, R5 and R5a optionally bears in each said CH2 or CH3 group one or more (for example 1, 2 or 3) of halogen subsides or a substituent selected from hydroxy and (1-3C) alkoxy; R6 is selected from hydrogen and alkyl (1-4C); A is a group of the formula Z- (CR12R13) P-, where p is 1 or 2, each R12 and R13, which may be the same or different, is selected from hydrogen and alkyl (1-4C), or a group R12 and R13 bound to the same carbon atom form a cycloalkyl ring (3-6C), and wherein any group CH2 or CH3 in any of R12 and R13 optionally carries in each said group CH2 or CH3 one or more (for example 1, 2 or 3) halogen substituents or a substituent selected from hydroxy, and (1-3C) alkoxy, Z is selected from hydrogen, OR1 5 and NR16R17, wherein each of R15, R16 and R17 which may be the same or different, is selected from hydrogen and alkyl (1-6C), and wherein any group CH2 or CH3 in a group Z optionally carries in each said group CH2 or CH3 one or more substituents of fluoro or chloro or a substiuent selected from hydroxy, (2-4C) alkenyl, (2-4C) alkynyl and (1-4C) alkoxy; or a pharmaceutically acceptable salt thereof. In one embodiment, in the compound of the formula Ib, R3a is selected from hydrogen, chlorine and alkyl (1 -3C), particularly R3a is chloro or alkyl (1 -3C) (such as methyl), more particularly R3a is chloro. In another embodiment, in the compound of the formula Ib, Q1 is selected from phenyl optionally subsituted with 1 or 2 substituents selected from fluoro and chloro, or Q1 is selected from 2-pyridyl, 3-pyridyl, 2-pyrazinyl, 1, 3 -thiazol-2-yl, 1,3-thiazol-4-yl, 1,3-thiazol-5-yl and isoxazol-3-yl (particularly 2-pyridyl, 3-pyridyl, 2-pyrazinyl, 1, 3- thiazol-2-yl, 1,3-thiazol-4-yl and isoxazol-3-yl), and wherein Q1 optionally bears 1, 2, or 3 substituents, which may be the same or different, selected from halogen (by example fluoro or chloro), hydroxy, alkyl (1-4C) and alkoxy (1-4C). In another embodiment, in the compound of the formula Ib, Q1 is pyridyl (for example 2-pyridyl or 3-pyridyl, particularly 2-pyridyl). In another embodiment, in the compound of the formula Ib, R4, R4a, R5 and R5a are selected from hydrogen and alkyl (1 -3C), for example R4, R4a, R5 and R5a are selected from hydrogen and methyl. In another embodiment, in the compound of the formula Ib, R4, R4a, R5 and R5a are all hydrogen. In another embodiment, in the compound of formula Ib, R4, R5 and R5a are hydrogen and R4 is alkyl (1-3C), for example methyl. In another embodiment, in the compound of the formula Ib, R4, R5 and R5a are hydrogen and is alkyl (1-3C), for example methyl. In another embodiment, in the compound of the formula Ib, R 4 and R4a are both hydrogen and R5 and R5a are both (1 -3C) alkyl, for example methyl. In another embodiment, in the compound of the formula Ib, R6 is selected from hydrogen, methyl, ethyl, 2-hydroxyethyl, 2-methoxyethyl, propyl, isopropyl, allyl, 2-propynyl, cyclopropyl, cyclobutyl, piperidinyl, tetrahydropyranyl and cyclopropylmethyl, and wherein any CH2 group in a cycloalkyl group in R6 optionally bears in each CH2 group 1 or 2 subsifiuyenles selected from hydroxy, meily, ethyl, methoxy and ethoxy, and wherein any heterocyclyl group in R6 optionally bears one or more substituents, which it may be the same or different, selected from fluoro, chloro, bromo, oxo, hydroxy, methyl, ethyl, propyl, isopropyl, trifluoromethyl, methoxy, ethoxy, propoxy, isopropoxy and trifluoromethoxy. In another embodiment, in the compound of the formula Ib, A is a group of the formula Z- (CR12R1 3) P- where p is 1 or 2, each R12 and R13, which may be the same or different, is selected of hydrogen and alkyl (1-4C), or a group R12 and R13 attached to the same carbon atom form a cycloalkyl ring (3-6C), and wherein any CH2 or CH3 group in any of R12 and R13 optionally carries in each said group CH2 or CH3 one or more (for example 1, 2 or 3) substituents of halogen or alkyl (1-4C) or a substituent selected from hydroxy and alkoxy (1-4C), and wherein Z is selected from hydrogen , OR15, NR16R17 and alkylsulfonyl (1-6C), wherein each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-4C) and alkoxycarbonyl (1-4C). For example, in one embodiment, Z is selected from hydrogen, hydroxy, methoxy, N-meitylamino, N, N-dimethylamino, (N-methyl) - (N-tert-butoxycarbonyl) amino and methylsulfonyl ( particularly Z is hydroxy). In another embodiment, in the compound of the formula Ib, A is a group of the formula Z- (CR12R13) P-, where p is 1 or 2, each R12 and R13, which may be the same or different, is selected of hydrogen and alkyl (1-4C), or a group R 2 and R 13 attached to the same carbon atom form a cycloalkyl ring (3-6C), and wherein any CH 2 or CH 3 group in any of R12 and R13 optionally carries in each said group CH2 or CH3 one or more (for example 1, 2 or 3) halogen substituents or alkyl (1-4C) or a substiuent selected from hydroxy and (1-4C) alkoxy, and wherein Z is selected from hydrogen, hydroxy and (1-3C) alkoxy. For example Z is hydrogen or hydroxy, particularly Z is hydroxy. In another embodiment, in the compound of the formula Ib, A is selected from methyl and hydroxymethyl. Particularly A is hydroxymethyl. In another embodiment, in the compound of the formula Ib, A is a group of the formula Z- (CR12R13) P-, where p is 1 or 2, each R12 and R13, which may be the same or different, is selected of hydrogen and alkyl (1-4C), or a group R12 and R13 attached to the same carbon atom form a cycloalkyl ring (3-6C), and wherein Z is NR16R17, wherein each of R16 and R17 which can be the same or different, it is selected from hydrogen and alkyl (1-4C) (for example Z is selected from amino, JN-methylamino and JN.JN-dimethylamino, particularly Z is JN.JN-dimethylamino). In another embodiment, in the compound of the formula Ib: Q1 is pyridyl (for example 2-pyridyl); R3a is selected from chlorine and methyl (particularly R3a is chlorine); R4, R4a, R5 and R5a, which may be the same or different, are selected from hydrogen and methyl; and A is a group of the formula Z- (CR12R1 3) P-, where p is 1 or 2, each R12 and R13, which may be the same or different, is selected from hydrogen and alkyl (1 -3C) ( for example R12 and R13 are selected from hydrogen and methyl), and Z is selected from hydrogen, and hydroxy (particularly Z is hydroxy). A particular embodiment of the present invention is a quinazoline derivative of the formula I of the formula le: Ic wherein: R3a is selected from cyano, halogen, alkyl (1-4C), trifluoromethyl, alkoxy (1-4C), alkenyl (2-4C) and alkynyl (2-4C); n is 0, 1 or 2; each R3, which may be the same or different, is selected from cyano, halogen, alkyl (1-4C), trifluoromethyl, alkoxy (1-4C), alkenyl (2-4C) and alkynyl (2-4C); R3a is selected from halogen and alkyl (1-4C); R4, R4a, R5 and R5a, which may be the same or different, are selected from hydrogen and alkyl (1-6C), or R4 and R4a together with the carbon atom to which they are attached form a cycloalkyl ring (3- 7C), or R5 and R5a together with the carbon atom to which they are attached form a (3-7C) cycloalkyl ring, and wherein any CH2 or CH3 group in any of R4, R4a, R5 and R5a optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) substituents of halogen or a substituent selected from hydroxy, cyano, (1-6C) alkoxy, amino, (2-6C) alkanoyl, alkylamino (1-6C) ) and di- [alkylamino (1 -6C)]; R6 is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalky (3-7C) -alkyl (1-6C), cycloalkenyl ( 3-7C), cycloalkenyl (3-7C) -alkyl (1-6C), heterocyclyl and heterocyclyl-alkyl (1-6C), and wherein any heterocyclyl group in a substituent R6 optionally carries one or more substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C) , alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, (2-6C) alkanoyl, alkanoyloxy ( 2-6C) and a group of the formula: wherein X3 is a direct bond or is selected from O, CO, SO2 and N (R11), wherein R11 is hydrogen or alkyl (1-4C), and R10 is halogen-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C), JN-Alkylamino (1-4C) -alkyl (1-4C) ), and JN, JN-di- [alkyl (1-4C)] amino-alkyl (1-4C), and wherein any heyerocyclyl group in a substituent R6 optionally carries 1 or 2 substituents oxo or fioxo; and wherein any CH2 or CH3 group in a R6 substituent, differentiates a CH2 group in a heterocyclyl group, optionally carries in each said CH2 or CH3 group one or more halogen substituents or (1-6C) alkyl or a substituent selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1 -6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, N-alkylcarbamoyl (1-6C), JN, N-di [(1-6C) alkyl] carbamoyl, alkanoyl (2C) -6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), N-alkyl (1-6C) -alkylamino (2-6C), N-alkylsulfamoyl (1-6C), N, N-di [alkyl (1-6C)] suIfamoil, alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonamino (1-6C); A is selected from hydrogen, a group of the formula Z- (CR12R13) P- and R14, wherein p is 1, 2, 3, or 4, each R12 and R13, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl (2-6C), or a group R12 and R13 attached to the same carbon atom form a ring of cycloalkyl (3-7C) or cycloalkenyl (3-) 7C), and wherein any CH2 or CH3 group in any of R12 and R13 optionally carries in each said CH2 or CH3 group one or more (for example 1, 2 or 3) halogen or alkyl (1-6C) substituents or a substituent selected from hydroxy, cyano, alkyl (1-6C), alkoxy (1-6C), amino, alkanoyl (2-6C), alkylamino (1-6C) and di- [alkyl (1-6C)] amino, Z is selected from hydrogen, OR15, NR16R17, alkylsulfonyl (1-6C), alkanesulfonylamino (1-6C) and N-alkyl (1-6C) -alkanesulfonamino (1-6C), wherein each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2- 6C) and alkoxycarbonyl (1-6C), or Z is a group of the formula: Q2-X4- wherein X4 is selected from O, N (R18), SO2 and SO2N (R18), wherein R18 is hydrogen or alkyl (1 -6C), and Q2 is cycloalkyl (3-7C), cycloalkenyl (3-7C) or heterocyclyl, R14 is selected from hydrogen, OR19 and NR16R17, wherein R19 is selected from alkyl (1-6C), alkenyl ( 2-6C) and alkynyl (2-6C), and wherein R16 and R17 are as defined above, or R14 is a group of the formula: Q3-X5-wherein X5 is selected from O and N (R20), wherein R20 is hydrogen or alkyl (1-6C), and Q3 is cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1 - 6C), cycloalkenyl (3-7C), cycloalkenyl (3-7C) -alkyl (1-6C), heterocyclyl and heterocyclyl-alkyl (1-6C), or R14 is Q4 wherein Q4 is cycloalkyl (3-7C) , (3-7C) cycloalkyl-(1-6C) alkyl, (3-7C) cycloalkenyl, (3-7C) cycloalkenyl (1-6C), heterocyclyl or heterocyclyl-alkyl (1-6C), and wherein adjacent carbon atoms in any alkylene chain (2-6C) in a substituent Z or R14 are optionally separated by the insertion in the chain of a selected group of O, S, SO, SO2, N (R21), CO, - C = C and -C = C-, wherein R21 is hydrogen or alkyl (1-6C), and wherein any heterocyclyl group in a substituent Z or R4 optionally bears one or more (for example 1, 2 or 3) subsitutes, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1 -6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkyl (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino ( 1 -6C), di- [alkyl (1-6C)] amino, (2-6C) alkanoyl, (2-6C) alkanoyloxy, and a group of the formula: -X6-R22 wherein X6 is a direct bond or is selected from O, CO, SO2 and N (R23), wherein R23 is hydrogen or alkyl (1-4C), and R22 is halo-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy ( 1 -4C) -alkyl (1-4C), cyanoalkyl (1-4C), amino-alkyl (1-4C), N-alkylamino (1-4C) -alkyl (1-4C), and N, N -di [alkyl (1-4C)] amino-alkyl (1-4C), and wherein any heterocyclyl group in a substituent Z or R14 optionally carries 1 or 2 oxo or thioxo substituents, and wherein any CH2 or CH3 group in a group Z or R14, other than a CH2 group on a heterocyclyl ring, optionally carries in each said group CH2 or CH3 one or more halogen or alkyl (1-6C) subsififuents or a substituent selected from hydroxy, cyano, amino, carbo xi, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino ( 1 -6C), di- [alkyl (1 -6C)] amino, JN-alkylcarbamoyl (1 -6C), JN, JN-di [(1-6C) alkyl] carbamoyl, (2-6C) alkanoyl, alkanoyloxy ( 2-6C), alkanoylamino (2-6C), JN-alkyl (1 -6C) -alkylamino (2-6C), JN-alkylsulfamoyl (1 -6C), N., N.-di [alkyl (1-6C) )] sulfamoyl, alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C); or a pharmaceutically acceptable salt thereof. In another embodiment, in the compound of the formula le, n is 0 and R3a is selected from halogen, trifluoromethyl, alkyl (1-4C), alkoxy (1-4C), alkenyl (2-4C) and alkynyl (2-4C) ). Particularly R3a is selected from halogen and alkyl (1 -3C), more particularly R3a is selected from chloro and methyl, even more particularly R3a is chloro. In this mode n is properly 0 or 1. Parficularly n is 0. In another embodiment, in the compound of the formula le, R3c is alkyl (1-4C), particularly mephile.

In another embodiment, in the compound of the formula le, R, R4a, R5 and R5a, are selected from hydrogen and alkyl (1 -3C), for example R4, R4a, R5 and R5a are selected from hydrogen and methyl. In another embodiment, in the compound of the formula le, R4, R4a, R5 and R5a iodos are hydrogen. In another embodiment, in the compound of the formula le, R 4, R 5 and R 5a are hydrogen and R 4 is alkyl (1 -3C), for example methyl. In another embodiment, in the compound of the formula le, R 4, R 4a and R 5a, is alkyl (1 -3C), for example meily. In other modality, in the compound of the formula le, R4 and R4a are both hydrogen and R5 and R5a are both (1 -3C) alkyl, for example methyl. In another embodiment, in the compound of the formula le, R6 is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalkyl (3- 7C) -alkyl (1-6C), heterocyclyl and heterocyclyl-alkyl (1-6C), wherein any heterocyclyl group in R6 is a partially saturated or saturated monocyclic heterocyclyl ring., 5, 6 or 7 members containing 1 or 2 heteroatoms selected from oxygen, nitrogen and sulfur, and wherein any heterocyclyl group in a R6 substituent optionally carries one or more substituys, which may be the same or different, selected from halogen, trifluoromethyl , hydroxy, amino, alkyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylamino (1-6C), di- [(C 1-6C)] amino, alkanoyl (2) -6C), and from a group of the formula: _X _ R10 wherein X3 is a direct bond or is selected from O and N (R11), wherein R1 1 is hydrogen or alkyl (1-4C), and R1 0 is halogen-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C) , N-alkylamino (1-4C) -alkyl (1-4C) and N, N-di- [alkyl (1-4C)] aminoalkyl (1-4C), and wherein any heterocyclic group in a substifuyeníe R6 optionally carries 1 or 2 oxo subsfituyentes. In another embodiment, in the compound of the formula le, R6 is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalkyl (3- 7C) -alkyl (1-4C), heterocyclyl and heterocyclyl-alkyl (1-4C), wherein any heterocyclyl group in R6 is a partially saturated, saturated or monocyclic saturated heterocyclic ring of 4, 5, 6 or 7 members containing 1 or 2 heteroatoms selected from oxygen, nitrogen and sulfur, and wherein any heterocyclyl group in a sub-affinity R6 optionally bears one or more substituents, which may be the same or different, selected from fluoro, chloro, bromo, hydroxy, alkyl (1 -4C), alkenyl (2-4C), alkynyl (2-4C) and alkoxy (1-4C), and wherein any heterocyclyl group in a substituent R6 optionally carries 1 oxo substituent, and wherein any CH2 group or CH3 in a substituent R6, different from a group CH2 in a heterocyclyl group, optionally carries in each said group CH2 or CH3 one or more substituents selected from fluoro and chloro, or a substituent selected from hydroxy and alkoxy (1-4C), alkylamino and di- [alkyl (1 -6C)] amino. In another embodiment, in the compound of the formula le, R6 is selected from hydrogen, methyl, ethyl, 2-hydroxyethyl, 2-methoxyethyl, propyl, isopropyl, allyl, 2-propynyl, cyclopropyl, cyclobutyl, piperidinyl, hydroxyaryl and cyclopropylmethyl, and wherein any CH2 group in a cycloalkyl group in R6 optionally carries in each CH2 group 1 or 2 substituents selected from hydroxy, methyl, ethyl, methoxy and eioxy, and wherein any heterocyclic group in R6 optionally bears one or more substituents, which it can be the same or different, selected from fluoro, chloro, bromo, oxo, hydroxy, methyl, ethyl, propyl, isopropyl, trifluoromethyl, methoxy, ethoxy, propoxy, isopropoxy and urea fluoride. In another modality, in the compound of the formula le, A is a group of the formula Z- (CR12R13) p-, where p is 1 or 2, each R12 and R13, which may be the same or different, is selected of hydrogen and alkyl (1-4C), or a group R 2 and R 13 attached to the same carbon atom form a cycloalkyl ring (3-6C), and wherein any CH 2 or CH 3 group in any of R 12 and R 13, optionally it carries in each said group CH2 or CH3 one or more (for example 1, 2 or 3) substituents of halogen or alkyl (1-4C) or a substituent selected from hydroxy and alkoxy (1-4C), and wherein Z is selected of hydrogen, OR15, NR16R17 and alkylsulfonyl (1-6C), wherein each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-4C) and alkoxycarbonyl (1-4C) ). For example, in one embodiment, Z is selected from hydrogen, hydroxy, methoxy, N-methylamino, N, N-dimethylamino, (N-methyl) - (N-tert-butoxycarbonyl) amino and methylsulfonyl (particularly Z is hydroxy). A parficular compound of the invention is, for example, one or more quinazoline derivatives of the formula I selected from:? / -. { 2 - [(4- {3-chloro-4- (pyridin-2-ylmeyoxy) anilino} quinazolin-5-yl) oxy] ethyl} -2-methoxy -? / - methylacetamide; ? / -. { 2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] etiI} -2- (dimethylamino) -? / - methyllacetamide; ? / -. { (29) -2 - [(4-. {3-Chloro-4- (pyridin-2-ylmeyoxy) anilino} quinazolin-5-l) oxy] propyl} -2-methoxy -? / - methylacetamide; 2-hydroxy -? / - methyl -? / -. { 2 - [(4- {3-meityl-4- (pyrazin-2-ylmeyoxy) anilino} quinazolin-5-yl) oxy] elil} acef amide; 2-hydroxy -? / - methyl -? / -. { 2 - [(4- {3-methyl-4- (1, 3-yiazol-4-ylmethoxy) anilino} quinazolin-5-yl) oxy} ethyl} acef amide; 2-hydroxy -? / - methyl -? / - (2- { [4- (3-methyl-4 - [(5-methylisoxazol-3-yl) methoxy] anilino) quinazolin-5-yl] oxy] ethyl) acetamide; ? / -. { (2f?) - 2 - [(4. {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} -2-methoxyacetamide; ? / - (2- { [4- (3-chloro-4 - [(6-methylpyridin-2-yl) mephoxy] anilino) quinazoIin-5-yl] oxy}. Eyl) -2-hydroxy- ? / - methylaceaemide; ? / - ((2R) -2- { [4- (3-chloro-4 - [(6-meilypyridin-2-yl) methoxy] anilino) quinazolin-5-yl] oxy}. Propyl) - 2-hydroxy -? / - meyilaceiamide; ? / - (2- {[[4- (3-chloro-4 - [(6-mepylpyridin-2-yl) methoxy] anilino) quinazolin-5-yl] oxy} ethyl) -? / - methylacefamide; ? / - (2- {[[4- (3-chloro-4 - [(2-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy} ethyl) - / V-meitylazefamide; ? / - (2- { [4- (3-chloro-4 - [(3-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy} ethyl) - / V-methylacetamide; ? / -. { 2 - [(4- {3-chloro-4- (1, 3-thiazol-4-ylmethoxy) anilino} quinozin-5-yl) oxy] eyl} -? / - methylaceaemide; ? / -. { 2 - [(4-. {3-Chloro-4- (pyrazin-2-ylmeyoxy) anilino} quinazolin-5-yl) oxy] ethyl} -? / - methylacetamide; ? / -. { (2 /?) - 2 - [(4. {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} -2-hydroxyacetamide; ? / -. { 2 - [(4-. {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} - -methylacetamide; 2-hydrox / -? / - methyl- / -. { 2 - [(4- {3-methyl-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} acef amide; ? / -. { (1 R) -2 - [(4-. {3-Chloro-4- (pyridin-2-ylmeyoxy) anilino} quinazolin-5-yl) oxy] -1-methylethyl} acetamide; ? / -. { (1 R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] -1-methyl-ethyl} -2-hydroxy acetamide; ? / -. { 2 - [(4-. {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy -? / - methylacetamide; ? / - (2- { (4- (3-chloro-4 - [(3-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy} ethyl) -2-hydroxy-? / -methylacetamide;? / - { 2 - [(4- { 3-Chloro-4- (1, 3-yiazol-4-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl]. 2-hydroxy -? / - mefilacetamide;? / - { 2 - [(4- {3-chloro-4- (pyrazin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] efil .} - 2-hydroxy -? / - meitylacetamide;? / - { 2 - [(4. {3-chloro-4- (pyridin-2-ylmeyoxy) anilino}. Quinazolin-5-yl. ) oxy] efil.} acetylamide;? / - { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmefoxy) anilino} quinazolin-5-yl ) oxy] propyl} acetamide;? / -. {(2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anionic} quinazolin-5 -yl) oxy] propyl.} -2-hydroxy- / V-methylacetamide;? / - { (2f?) - 2 - [(4- { 3-chloro-4- (prazni- 2-ylmethoxy) anilino} quinazolin-5-i I) oxy] propyl} -2-hydroxy- / V-methyl I acetamide;? / - ((2 /?) -2- { [4 - (3-chloro-4 - [(3-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy} propyl) -2-hydroxy-γ / -methylacetamide;? / -. {(2R) - 2 - [(4- { 3-chloro-4- ( 1,3-thiazole-4-i I methoxy) indigo ino} quinazoli n-5-yl) oxy] propyl} -2-hydroxy -? / - methylacetamide; ? / -. { (2R) -2 - [(4. {3-chloro-4- (pyridin-2-ylmefoxy) anilino} quinazolin-5-yl) oxy] propyl} -? / - mefilacefamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} - / V-efilacetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5- ii) oxy] ethyl} -? / - ethyl-2-hydroxyacetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - propylacetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy- / V-propylacetamide; ? / -. { 2 - [(4- {[3-chloro-4- (pyridin-2-ylmefoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - iso propyl acetamide; / V-. { 2 - [(4- {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy -? / - isopropylacetamide; ? / - alil -? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; / V-alil -? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxyacetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazoIin-5-yl) oxy] ethyl} -? / - cyclopropylacetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - cyclopropyl-2-hydroxyaceiamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmefoxy) phenyl] amino} quinazolin-5-yl) oxy] eyl} -? / - (cyclopropylmethyl) acetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - (cyclopropylmethyl) -2-hydroxyacetamide; / V-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - cyclobutylacetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - cyclobutyl-2-hydroxyacetamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] efil} } -? / - (1-methylpiperidin-4-yl) acetylamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] efil} } -? / - (tetrahydro-2H-pyran-4-yl) acetamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} } -2-hydroxy -? / - (teirahydro-2H-pyran-4-i I) acetamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} } -? / - (2-hydroxief¡]) acef amide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} } -2-hydroxy -? / - (2-hydroxyethyl) acetamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} } -? / - (2-methoxyethyl) acetamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] efil} } -2-hydroxy -? / - (2-meioxyethyl) acetamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} } -? / - prop-2-in-1 -i I acetamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} } -2-hydroxy -? / - prop-2-in-1-ylacetamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} } -2-hydroxy -? / - methylpropanamide; / V-. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} } -? / - methyl-tetrahydrofuranyl-2-carboxamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} } -N, 1 -di mef i I prolinamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} -2-hydroxy -? /, 2-dimethylpropanamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -1-hydroxy -? / - methylcyclopropanecarboxamide; ? / í-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? /?,? / 2-dimethylglycinamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -3-h id roxi -? /, 2, 2-tri-methyl propan amide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -3-hydroxy- / V-methylpropanamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazoIin-5-yl) oxy] propyl} acetamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxyacetamide; ? / í-. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / 2,? / 2-dimethylglycinamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-mexoxyacefamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2- (methylsulfonyl) acetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] eyl} -2-hydroxyacefamide; ? / í-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / 2,? / 2-dimethylglycinamide; ? / -. { 2 - [(4- {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] eti} -2-methoxyaceta measure; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2- (methylsulfonyl) acetamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / - methylacetamide; ? / -. { (2S) -2 - [(4. {[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxy -? / - meth I acetamide; ? / í-. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / 1,? / 2,? / 2-trimethylglycinamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amine} quinazolin-5-yl) oxy] propyl} -2-methoxy -? / - methylacetamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / - mephyl-2- (methylsulfonyl) acetamide; ? / -. { (2 c?) - 2 - [(4- {[[3-chloro-4- (pyrazin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / - methylacetamide; / V-. { (2f?) - 2 - [(4- {[3-chloro-4- (1,3-thiazol-4-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / - methylaceaemide; ? / - ((2R) -2-. {(4- ( { 3-chloro-4 - [(3-fluorobenzyl) oxy] phenyl} amino) quinazolin-5-yl] oxy}. propyl) -? / - methylacetamide; / V - ((2R) -2-. {(4- ( { 3-chloro-4 - [(2-fluorobenzyl) oxy] phenyl}. amino) quinazolin- 5-yl] oxy}. Propyl) -? / - methylacetamide;? / - { (1 R) -2 - [(4- {[3-chloro-4- (pyridin-2-ylmefoxy) phenyl] amino} quinozolin-5-yl) oxy] -1-methylphylethyl} -2-hydroxy-? / - meitylacetamide; N- { (1 R) -2 - [(4 - { [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] -1-methylethyl.} -? / - m ethyl acetamide; - { (1 S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl .} -2-hydroxy -? / - methylacetamide;? / - { (1 S) -2 - [(4. {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] am No.}. Quinazoln-5-yl) oxy] -1-methylethyl.} -? / - m ethyl acetamide;? / - { (1 S) -2 - [(4- { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino.} Quinazolin-5-yl) oxy] -1-methyl-ethyl} -2-mephoxy-β-methylacefamide; . (1 S) -2 - [(4- {[3-chloro-4- (pyridin-2-ylmetox i) phenyl] amino} quinazolin-5-yl) oxy] -1-methyleryl} -2-hydroxyaceiamide; ? / -. { (1 S) -2 - [(4. {[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methylethyl} acetamide; ? / í-. { (1 S) -2 - [(4. {[3-chloro-4- (pyridin-2-ylmeyoxy) phenyI] amino} quinazolin-5-yl) oxy] -1-methylphilethyl} -? / 2,? / 2-dimethylglycine amide; ? / í-. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / 2,? / 2-dimethylglycinamide; (2S) -? / -. { 2 - [(4- {[3-cioro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2,4-dihydroxybutanamide; (2R) - -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ei i l} -2, 4-d i hydroxy bufan amide; (2R) -? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4-dihydroxybutanamide; (2S) -? / -. { (2R) -2-I (4- { _3-chloro-4- (pyridn-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] propyl} -2,4-dihydroxybutanamide; (2/?)-?/-. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4- dihydroxy butan amide; (2S) -? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4-dihydroxybutanamide; (2S) -? / -. { (1 R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyleryl} -2,4-dihydroxibulanamide; (2R) -? / -. { (1 R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} -2,4-dihydroxybutanamide; (2f?) - / V-. { 2 - [(4- {[3-chloro-4- (1, 3-thiazol-4-ylmefoxy) phenyl] amino} quinazolin-5-yl) oxy] efil} -2,4-dihydroxybuanamide; (2S) - / V-. { 2 - [(4. {[3-chloro-4- (1, 3-yiazol-4-ylmefoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2,4-dihydroxybuanamide; (2R) - / V-. { (1 ft) -2 - [(4- {[3-chloro-4- (1, 3-yiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl ethyl } -2,4-dihydroxybutanamide; (2S) -? / -. { (1 R) -2 - [(4- {[3-chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl } -2,4-dihydroxybutanamide; ? / - methyl- / V-. { 2 - [(4- {[[3-meityl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / - methyl- / V-. { 2 - [(4- {[3-methyl-4- (1, 3-thiazol-4-ylmefoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetylamide; / V-meityl- / V- (2- { [4- ( { 3-meityl-4 - [(5-methylisoxazol-3-yl) methoxy] phenyl} amino) quinazolin-5-yl. ] oxy] ethyl) acetamide; 2-hydroxy -? / - methyl -? / -. { 2 - [(4- {[3-methyl-4- (1, 3-thiazol-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] elil} acetamide; 2-hydroxy -? / -. { 2 - [(4- {[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; 2-hydroxy -? / -. { 2 - [(4- {[3-methyl-4- (1, 3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy} ethyl} acetylamide; ? / -. { 2 - [(4- {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1,1 -dimethylethyl} -2-hydroxyacetamide; 2-hydroxy -? / -. { (2R) -2 - [(4- {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; 2-hydroxy -? / -. { (2R) -2 - [(4- {[3-methyl-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetylamide; ? - ((2R) -2- { [4- ( { 4 - [(3-Fluorobenzyl) oxy] -3-methylphenyl}. Amino) quinazoIin-5-yl] oxy}. Propyl) - 2-hydroxyacetamide; 2-hydroxy -? / -. { (2R) -2 - [(4- {[3-methyl-4- (1, 3-thiazol-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; ? / -. { (2R) -2 - [(4- {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acef amide; ? / -. { (2R) -2 - [(4- {[3-methyl-4- (1, 3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acefamide; ? / - ((2R) -2- { [4- ( { 4 - [(3-Fluorobenzyl) oxy] -3-methylphenyl} amino) quinazolin-5-yl] oxy} propyl acefamide; ? / -. { (2R) -2 - [(4- {[3-methyl-4- (1, 3-thiazol-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; 2-hydroxy- / V-methyl -? / -. { (2R) -2 - [(4- {[3-meityyl-4- (pyridin-2-lmetoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; 2-hydroxy- / V-methyl -? / -. { (2R) -2 - [(4- {[3-methyl-4- (1, 3-yiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; 2-hydroxy -? / - methyI -? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(5-methylisoxazol-3-yl) methoxy] phenyl} amino) quinazolin-5-yl] oxy}. propyl) acetamide; / V-methyl- / V-. { (1 R) -1-methyl-2 - [(4. {[[3-meth] l-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / - methyl -? / -. { (1 R) -1-methyl-2 - [(4- {[[3-methyl-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinine-5- il) oxy] efil} acetamide; ? / -. { (1 R) -2 - [(4- {[3-chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1 - methyleryl } -2-hydroxy -? / - methylacecemide; 2-hydroxy -? / - methyl -? / -. { (1 R) -1-methyl-2 - [(4. {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetylamide; 2-hydroxy- / V-melil- / V-. { (1 R) -1 -meM-2 - [(4- {[[3-methyl-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -1-hydroxy -? / - methylcyclopropanecarboxamide; (2S) -? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxy- / V-methylpropanamide; ? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxy -? /, 2-d imefil pro pana mide; (2R) -? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxy -? / - methylpropanamide; (2R) -? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-methoxy -? / - methylpropanamide; 2-hydroxy -? / - methyl -? / - ((2R) -2- { [4 - ([3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl}. ) quinazolin-5-yl] oxy}. propyl) acetamide; ? / - methyl -? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl.} amino) quinazoline -5-yl] oxy}. Propyl) aceia ida; ? I, N2,? / 2-yrimethyl-N1 - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl .}. amino) quinazolin-5-yl] oxy}. propyl) glycinamide; ? / - methyl -? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl.} amino) quinazoline -5-yl] oxy}. Propyl) -2-pyrrolidin-1-ylacetamide; ? / - meyil -? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazoline -5-yl] oxy}. Propyl) -2-morpholin-4-ylazefamide; ? / - methyl -? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazoline -5-yl] oxy}. Propyl) -2- (4-methylpiperazin-1-yl) acetamide; 2-hydroxy -? / - methyl -? / - ((2S) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazolin-5-yl] oxy}. propyl) acetamide; ? / -methyl-? / - ((2SJ-2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl}. amino) quinazolin-5-yl] oxy}. propyl) acetamide;? / - methyl -? / - ((2S) -2- { [4- (. {3-methyl-4 - [(6-meilypyridin -3-yl) oxy] phenyl.}. Amino) quinazolin-5-yl] oxy}. Propyl) -2-pyrrolidin-1-alaceiamide; (2S) -2,4-dihydroxy-? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazoIin-5-yl] oxy}. propyl) butanamide; (2S) -4-bromo-2-hydroxy-N - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-meilypyridin-3-yl) oxy] phenyl .}. amino) quinazolin-5-yl] oxy}. propyl) butanamide; W- (2-chloroethyl) -? / '- ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazolin-5-yl] oxy}. propyl) urea; 2-hydroxy -? / - methyl-N - ((1 R) -1-methyl-2 { [4- ( { 3-methy-4 - [(6-methylpyridin-3-yl) oxy] ] phenyl} amino) quinazolin-5-yl] oxy}. ethyl) acetylamide; ? / - methyl -? / - ((1 R) -1-methyl-2- { [4- ( { 3-meityl-4 - [(6-meilypyridin-3-yl) oxy] phenyl} amino) quinazolin-5-yl] oxy}. eyl) acetylamide; 2-hydroxy -? / - mephyl -? / - ((1 S) -1-methyl-2- { [4- ( { 3-meyyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl.}. amino) quinazolin-5-yl] oxy} ethyl) acetamide; ? / - methyI-? / - ((1 S) -1-methyl-2 { [4- ( { 3-meiyl-4 - [(6-meilypyridin-3-yl) oxy] phenyl} amino) quinazolin-5-yl] oxy} ethyl) acetamide; methyl-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinozolin-5-yl) oxy] ethyl} methylcarbamate; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy ] ethyl} -? /, / V '-dimethyl urea; ? / '- (2-chloroethyl) -? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} - V-meyilurea; ? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmehoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / '- methylurea; Acid [((R) -2- { 4- [3-chloro-4- (pyridin-2-ylmethoxy) phenylamino] quinazolin-5-yloxy}. Propylcarbamoyl) mephile) mefylcarbamic eery-builyl ester; ?/1-. { (2R) -2- (4- { [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazo m-5-yl) oxy] propyl} -N2-melilglicinamide; 2-hydroxy- / V-methyl-? / - (2 { [4- ( { 3-methyl-4 - [(6-meilypyridin-3-yl) oxy] phenyl} amino) quinazoline -5-yl] oxy} ethyl) acetamide; ? / - methyl -? / - (2- { [4- ( { 3-meityl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazolin-5-yl. ] oxy] ethyl) acetamide; and N-. { 2 - [(4- {[3-chloro-4- (1-methyl-1-pyridin-2-yl-phoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -N-methylacetamide; or a pharmaceutically acceptable salt thereof A particular compound of the invention is, for example, one or more quinazoline derivatives of the formula selected from: ? / -. { 2 - [(4-. {3-Chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} -2-methoxy-N-methylacetamide; ? / -. { 2 - [(4-. {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} -2- (dimethylamino) -N-mellylacelamide; ? / -. { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazoIin-5-yl) oxy] propyl} -2-methoxy -? / - meth I acetamide); 2-hydroxy -? / - methyl -? / -. { 2 - [(4- {3-methyl-4- (pyrazin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} acelamide; 2-hydroxy -? / - meyil -? / -. { 2 - [(4-. {3-methyI-4- (1, 3-thiazol-4-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} acetamide; 2-hydroxy -? / - methyl -? / - (2 { [4- (3-methyl-4 - [(5-methylisoxazol-3-yl) methoxy] anilino) quinazolin-5-yl] oxy} ethyl) acetamide; ? / -. { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} -2-mephoxyacetamide; ? / - (2- {[4- (3-chloro-4 - [(6-methylpyridin-2-yl) methoxy] anilino) quinazolin-5-yl] oxy} ethyl) -2-hydroxy -N-methylacetamide; ? / - ((2R) -2- { [4- (3-chloro-4 - [(6-methylpyridin-2-yl) methoxy] anilino) quinazolin-5-yl] oxy}. Propyl) - 2-hydroxy -? / - methylacetamide; ? / - (2- {[[4- (3-chloro-4 - [(6-methylpyridin-2-yl) -methio] anilino) quinazolin-5-yl] oxy}. Efil) -N -methylaceiamide; ? / - (2- {[[4- (3-chloro-4 - [(2-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy} ethyl) -? / - mefilacetamide; ? / - (2- {[[4- (3-chloro-4 - [(3-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy} ethyl) -? / - mephilaceiamide; ? / -. { 2 - ((4- {3-chloro-4- (1, 3-fiazol-4-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} -? / - methyl I acetamide; ? / - {2 - [(4- { 3-Chloro-4- (pyrazan-2-ylmethoxy) anilino}. Quinazoln-5-yl) oxy] ethyl.} - ? / - methylacetamide;? / - { (2R) -2 - [(4- { 3-chloro-4- (pyridin-2-ylmethoxy) anilino}. quinazolin-5-yl) oxy] propyl .) -2-hydroxyaceiamide;? / - {2 - [(4. {3-chloro-4- (pyridin-2-ylmehoxy) anilino} quinazolin-5-yl) oxy] ethyl} -? / - methylacetamide; 2-hydroxy -? / - methyl -? / -. {2 - [(4- {3-methyl-4- (pyridin-2-ylmethoxy) anilino} quinazolin -5-yl) oxy] ethyl) acetamide; / V-. {(1 R) -2 - [(4. {3-chloro-4- (pyridin-2-ylmethoxy) anilino}. quinazolin-5-yl) oxy] -1-methylethyl.) acelamide;? / - { (1 R) -2 - [(4- { 3-chloro-4- (pyridin-2-ylmethoxy) anilino.}. quinazolin-5-yl) oxy] -1-methylethyl.} -2-hydroxyacetamide;? / -. {2 - [(4- { 3-chloro-4- (pyridin-2- ylmetoxy) anilino.}. quinazolin-5-yl) oxy] ethyl.} -2-hydroxy -? / - melamine lamellae;? / - (2- { [4- (3-chloro-4- [ (3-fluorobenzyl) oxy] anilino) q uinazolin-5-iI] oxy} ethyl) -2-hydroxy -? / - methylacetamide; ? / -. { 2 - [(4- {3-chloro-4- (1, 3-thiazol-4-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy-N-methylacetamide; ? / -. { 2 - [(4- {3-chloro-4- (pyrazin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy) ethyl} - 2-hydroxy -? / - methylacetamide; ? / -. { 2 - [(4-. {3-Chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy) efil} acetylamide; ? / -. { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) aniIino} quinazolin-5-yl) oxy] propyl} acetamide; ? / -. { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} -2-hydroxy -? / - methylacecemide; ? / -. { (2R) -2 - [(4- {3-chloro-4- (pyrazin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} -2-hydroxy -? / - methylacetamide; ? / - ((2R) -2- { [4- (3-chloro-4 - [(3-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy}. Propyl) -2-hydroxy- ? / - meyilaceiamide; ? / -. { (2R) -2 - [(4- {3-chloro-4- (1, 3-thiazol-4-ylmeyoxy) anilino} quinazoIin-5-yl) oxy] propyl} -2-h id roxi-N-meti I acetamide; -. { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propi} -? / - methylacetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - ethylacetamide; ? / -. { 2 - [(4- {[3-chloro-4- (pyridin-2-methyl-phenyl) -phenyl] -amino} quinazolin-5-yl) oxy] eti} -? / - ethyl-2-hydroxy acetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] eyl} -? / - propylacefamide; / V-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5- 2-hydroxy -? / - propylacetamide; 3-chloro-4- (pyridine) -2-ylmeyoxy) phenyl] amino.}. Quinazolin-5? / - isopropylacetamide; 3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino.}. Quinazolin-5- 2-hydroxy -? / - isopropylacetamide; - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-cetamide; - [(4- {[3-chloro-4} - (pyridin-2-ylmeyoxy) phenyl] amino.} quinazolin-5- 2-hydroxyaceiamide; 3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino}. quinazolin-5-? / - cyclopropylaceaemide; [3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino.}. Quinazplin-5? / - cyclopropyl-2-hydroxyaceiamide; [3-chloro-4- (pyridin-2-ylmefoxy) phenyl] amino} quinazolin-5-? / - cyclopropylmethyl) acetylamide; [3-chloro-4- (pyridin-2-ylmehoxy) phenyl] amino} quinazolin-5-? / - (cyclopropylmethyl) -2-hydroxyacetamide; 3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-? / - cyclobuphylacetamide; 3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-? / - cyclobufyl-2-hydroxyaceiamide; 3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-? / - (1-methylpiperidin-4-yl) acetamide; 3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazoIin-5- N- (ε-tetrahydro-2H-pyran-4-yl) acetamide; N-. { 2- [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) ox ethyl} } -2-h id roxi -? / - (íetrahydro-2H-pyran-4-i I) acetamide; ? / -. { 2- [(4- { { [3-chloro-4- (pyridin-2-ylmefoxy) phenyl] amino}. Quinazolin-5-I) OXY; eil } } -? / - (2-h id roxiet i I) acetamide; ? / -. { 2- I (4- { { [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5- i) oxy; eil } } -2-hydroxy-N- (2-hydroxy-yl) -acetylamide; ? / -. { 2- [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino.}. Quinazolin-5- I I) OX ?; ethyl} } -? / - (2-methoxyeti I) acetamide; ? / -. { 2- [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-ii) ox ethyl} } -2-hydroxy -? / - (2-methoxy-ethyl) acetamide; ? / -. { 2- [(4- { { [3-chloro-4-pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-ii) or? ¡; ethyl} } -? / - prop-2-in-1-ylacetamide; ? / -. { 2- [(4- { { [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5- i) oxy; ethyl} } -2-hydroxy -? / - prop-2-in-1 -i lame measure; ? / -. { 2- [(4- { { [3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino}. Quinazolin-5-M) ox ethyl} } -2-hydroxy -? / - methylpropanamide; ? / -. { 2- [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino.}. Quinazolin-5- i) or?; ethyl} } -? / - methyl-tetrahydrofuranyl-2-carboxamide; ? / -. { 2- I (4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-ii) oxy; eil } } -? /, 1-dimethylprolinamide; ? / -. { 2- [(4- { { [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5- i) oxy; eil } } -2-h id roxi -? /, 2-d i methyl pro pan amide; ? / -. { 2- [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-y I) oxT ethyl} } -1-hydroxy -? / - methylcyclopropanecarboxamide; ^ -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? /?,? / 2-dimethylglycinamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -3-h id roxy- / V, 2, 2-tri-methyl propan amide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -3-hydroxy-N-metylpropanamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetylamide; / V-. { (2S) -2 - [(4- {[3-Cyoro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-h id roxi aceta mida; ?/1-. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? /,? / 2-dimethylglycinamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-methoxyacetamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2- (methylsulfonyl) acetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazoIin-5-yl) oxy] ethyl} -2-hydroxyacetamide; / V1-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] eyl} -N2, N2-dimethylglycinamide; N-. { 2 - [(4- {[3-chloro-4- (pyridin-2-ylmefoxy) phenyl] amino} quinazolin-5-yl) oxy] eyl} -2-methoxy acetamide; ? / -. { 2 - [(4. {[3-Cyoro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] efil} -2- (meilylsulfonyl) acetylamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / - methylazepha measure; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxy- / V-mephilaceiamide; ? / í-. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / í,? / 2; ? / -trimethylglycinamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-methoxy -? / - methyl I acetamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -N-methyl-2- (methylsulfonyl) acetamide; ? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyrazin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / - meti I acetamide; ? / -. { (2R) -2 - [(4- {[3-chloro-4- (1, 3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / - met i I acetamide; ? / - ((2R) -2- { [4- ( { 3-Chloro-4 - [(3-fluorobenzyl) oxy] phenyl} amino) quinazolin-5-yl] oxy}. propyl) -? / - mephilaceiamide; ? / - ((2R) -2- { [4- ( { 3-chloro-4 - [(2-fluorobenzyl) oxy] phenyl} amino) quinazolin-5-yl] oxy} propyl) - / V-meti I aceta mida; ? / -. { (1) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-lefil} -2-hidrox¡ -? / - mef¡ lácela mida; ? / -. { (1) -2 - [(4- {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methylphylethyl} -? / - methylacetamide; ? / -. { (1S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} -2-hydroxy -? / - methylacetamide; ? / -. { (1S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} - / V-methylacetamide; ? / -. { (1 S) -2 - [(4. {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} -2-meioxy -? / - meyilacefamide; ? / -. { (1S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} -2-hydroxyacetamide; ? / -. { (1S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} acetamide; ? / í-. { (1S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} - 2,? / 2-dimethylglycinamide; ? / í-. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / 2, / V2-dimethyglycinamide; (2S) -? / -. { 2 - [(4- {[3-chloro-4- (pyridin-2-ylmefoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2,4-dihydroxybutanamide; (2R) -? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2, 4-d i hydroxy butan amide; (2R) -? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4-dihydroxybuanamide; (2S) -? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4-dihydroxybutan amide; (2R) -? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4-dihydroxybutanamide; (2S) -? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4-dihydroxybutanamide; (2S) -? / -. { (1 R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methylethyl} -2,4-d i hydroxy butan amide; (2R) -? / -. { (1 R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} -2,4-dihydroxybutanamide; (2R) -? / -. { 2 - [(4- {[3-chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2, 4-d i hydroxy butan amide; (2S) -? / -. { 2 - [(4- {[3-chloro-4- (1, 3-liazol-ylmethoxy) phenyl] amino} quininaiin-5-yl) oxy] ethyl} -2, 4-d i hydroxy butan amide; (2R) -N-. { (1 R) -2 - [(4- {[3-chloro-4- (1,3-thiazol-4-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methylene } -2,4-dihydroxybuanamide; (2S) -N-. { (1 R) -2 - [(4- {[3-chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl ethyl } -2,4-dihydroxybufanamide; ? / - methyl -? / -. { 2 - [(4- {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] etiI} acetamide; ? / - methyl -? / -. { 2 - [(4- {[3-methyl-4- (1, 3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy} ethyl} acetamide; ? / - methyl -? / - (2- {[[4- ( { 3-methyl-4 - [(5-methylisoxazol-3-yl) methoxy] phenyl} amino) quinazolin-5-yl. ] oxy] ethyl) acetamide; 2-hydroxy -? / - methyl -? / -. { 2 - [(4- {[3-methyl-4- (1, 3-yiazol-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy} eyl} acetylamide; 2-hydroxy -? / -. { 2 - [(4- {[[3-mephyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; 2-hydroxy -? / -. { 2 - [(4- {[3-methyl-4- (1, 3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy} ethyl} acef amide; ?F-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1, 1 -dimethylethyl} -2-hydroxyacetamide; 2-hydroxy -? / -. { (2R) -2 - [(4- {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; 2-hydroxy -? / -. { (2R) -2 - [(4- {[3-methyl-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; ? / - ((2R) -2- { [4- ( { 4 - [(3-Fluorobenzyl) oxy] -3-methylphenyl} amino) quinazolin-5-yl] oxy} propyl ) -2-hydroxyacetamide; 2-hydroxy -? / -. { (2R) -2 - [(4- {[3-methyl-4- (1, 3-thiazol-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetylamide; ? / -. { (2R) -2 - [(4- {[3-mephyl-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; ? / -. { (2R) -2 - [(4- {[3-meityl-4- (1, 3-yiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] pro pil} acetamide; ? / -. { (2R) -2-. { [4- ( { 4 - [(3-Fluorobenzyl) oxy] -3-methylphenyl}. Amino) quinazolin-5-yl] oxy} prop I) acetamide; ? / -. { (2R) -2 - [(4- {[3-methyl-4- (1, 3-yiazol-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; 2-hydroxy -? / - methyl -? / -. { (2R) -2 - [(4- {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; 2-hydroxy -? / - methyl -? / -. { (2R) -2 - [(4- {[3-methyl-4- (1, 3-thiazoI-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; 2-hydroxy- / V-methyl-N - ((2R) -2- { [4- (. {3-meityl-4 - [(5-methylisoxazol-3-yl) methoxy] phenyl}. amino) quinazolin-5-yl] oxy}. propyl) acetamide; ? / - methyl -? / -. { (1 R) -1-methyl-2 - [(4. {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / - methyl -? / -. { (1 R) -1-methyl-2 - [(4- {[3-meiyl-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / -. { (1 R) -2 - [(4- {[3-chloro-4- (1, 3-thiazol-4-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl } -2-hydroxy -? / - methylacecemide; 2-hydroxy -? / - methyl -? / -. { (1 R) -1-methyl-2 - [(4. {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; 2-hydroxy -? / - methyl -? / -. { (1 R) -1-methyl-2 - [(4- {[3-methyl-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} - 1-hydroxy -? / - melylcyclopropanecarboxa mida; (2S) -? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxy -? / - methylpropanamide; ? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazoIin-5-yl) oxy] propiI} -2-hydroxy -? /, 2-dimethylopropanamide; (2R) - V-. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxy-? -methylpropanamide; (2R) -? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-methoxy -? / - methylpropanamide; methyl-. { 2 - [(4- {[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-l) oxy] ethyl} methylcarbamate; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? /,? / '- dimethylurea; ? / '- (2-chloroethyl) -? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -N-methylurea; ? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amine} quinazolin-5-yl) oxy] propyl} -? / '- methylurea; Acid [((R) -2- { 4- [3-chloro-4- (pyridin-2-ylmethoxy) phenylamino] quinazolin-5-yloxy}. Propylcarbamoyl) methyl] methylcarbamic tert-butyl ester; ? / í-. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -N-2-methyglycinamide; and N-. { 2 - [(4- {[[3-chloro-4- (1-methyl-1-pyridin-2-ylethoxy) phenyl] amino} quinazolin-5-yl) oxy} ethyl} -? / - mefilacetamide; or a pharmaceutically acceptable salt thereof. A particular compound of the invention is, for example, one or more quinazoline derivatives of the formula Ib selected from: ? / -. { 2 - [(4-. {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} -2-mefoxy -? / - meíi I aceta mide; ? / -. { 2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] eyl} -2- (dimethylamine) -? / - mephilaceiamide; ? / -. { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-i I) oxy] pro pil} -2-methoxy -? / - meth I acetamide); 2-hydroxy -? / - methyl -? / -. { 2 - [(4-. {3-methyl-4- (pyrazin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] etl} acetylamide; 2-hydroxy- / V-methyl -? / -. { 2 - [(4- {3-methyl-4- (1, 3-yiazol-4-ylmethoxy) anilino} quinazolin-5-yl) oxy} ethyl} acetamide; 2-hydroxy-γ -methyl-? / - (2- { [4- (3-methyl-4 - [(5-methylisoxazol-3-yl) methoxy] anilino) quinazolin-5-yl] oxy} ethyl) acetamide; ? / -. { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} -2-methoxyacetamide; ? / - (2- { [4- (3-chloro-4 - [(6-methylpyridin-2-yl) methoxy] anilino) quinazolin-5-yl] oxy) ethyl) -2-hydroxy -? -methylacetamide; ? / - ((2R) -2- { [4- (3-chloro-4 - [(6-methylpyridin-2-yl) -methio] anilino) quinazolin-5-yl] oxy) propyl) -2- hydroxy -? / - methylacecemide; ? / - (2- {[[4- (3-chloro-4 - [(6-mepylpyridin-2-yl) methoxy] anilino) quinazolin-5-yl] oxy} ethyl) -? / - methylacefamide; ? - (2- { [4- (3-chloro-4 - [(2-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy} ethyl) -? / - methylacecemide; ? / - (2- { [4- (3-chloro-4 - [(3-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy]. Ethyl) -? / - methylacetamide; ? / -. { 2 - [(4- {3-chloro-4- (1, 3-thiazol-4-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} -? / - methylacetamide; ? / -. { 2 - [(4- {3-chloro-4- (pyrazin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} - / V-methylacetamide; ? / -. { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) aniIino} quinazolin-5-yl) oxy] propyl} -2-hydroxyacetamide; ? / -. { 2 - [(4-. {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} -? / - methylacetamide; 2-hydroxy -? / - meyil -? / -. { 2 - [(4-. {3-mephyl-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy) ethyl} acetamide; ? / -. { (1 R) -2 - [(4- { 3-Chloro-4- (pyridin-2-ylmethoxy) anilino}. Quinazolin-5-yl) oxy] -1-methylethyl} acetamida; ? / -. { (1 R) -2 - [(4- { 3-Chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] -1-methylethyl} -2-hydroxyacefamide; ? / -. { 2 - [(4- {{3-chloro-4- (pyridin-2-ylmefoxy) anilino} quinazolin-5-yl) oxy] eiI} -2-hydroxy -? / - methylacetamide; ? / - (2- { [4- (3-chloro-4 - [(3-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy} ethyl) -2-hydroxy -? -methylacetamide; ? / -. { 2 - [(4- {3-chloro-4- (1, 3-thiazol-4-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy -? / - methylacetamide; ? / -. { 2 - [(4- {{3-chloro-4- (pyrazin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy]] yl} - 2-hydroxy-N-methylacetamide; ? / -. { 2 - [(4-. {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / -. { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} acefamide; ? / -. { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} -2-hydroxy -? / - methylacecemide; ? / -. { (2R) -2 - [(4- {3-chloro-4- (pyrazin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} -2-hydroxy -? / - methylacetamide; ? / - ((2R) -2- { [4- (3-chloro-4 - [(3-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy} propyl) -2-hydroxy- ? / - meyilaceiamide; ? / -. { (2R) -2 - [(4- {3-chloro-4- (1, 3-thiazol-4-ylmethoxy) anilino} quinazoIin-5-yl) oxy] propyl} -2-hydroxy -? / - methylacetamide; ? / -. { (2R) -2 - [(4. {3-chloro-4- (pyridin-2-ylmethoxy) aniIino} quinazolin-5-yl) oxi propyl} -? / - meti I aceta mida; ? / -. { 2- (4-. {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl} amino} quinazolin-5-yl) oxy ethyl} -? / - ethylacef amide; ? / -. { 2- (4- { [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy I. I. - W-et i I-2-h id roxy acetamide; ?F-. { 2- (4- { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy ethyl} -? / - propylacetamide; ? / -. { 2- (4- { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy ethyl} -2-hydroxy-W-propylacetamide; ? / -. { 2- (4- { [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy ethyl} -? / - isopropylacetamide; N-. { 2- (4- { [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. QuinazoIin-5-yl) oxy ethyl} -2-hydroxy -? / - isopropylacetamide; ? / - ali -? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy ethyl} acetamide; ? f-ali -? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy ethyl} -2-hydroxyacetamide; ? / -. { 2- (4- { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy ethyl} -? / - cyclopropyl acetamide; ? / -. { 2- (4- { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy ethyl} -? / - cyclopropylo-2-hydroxyacetamide; ? / -. { 2- (4- { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy ethyl} -? / - (cyclopropylmethyl) acetamide; ? / -. { 2- (4- { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} } -? / - (cyclopropylmethyl) -2-hydroxyaceiamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmehoxy) phenyl] amino}. Quinazolin-5-yl) oxy) ethyl} } -? / - cyclobuti I aceta mide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} } - / V-cyclobufil-2-hydroxyaceiamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} } -? / - (1-methylpiperidin-4-yl) acetamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} } -? / - (tetrah id ro-2 - -piran-4-i I) acetamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} } -2-hydroxy -? / - (tetrahydro-2 / - / - pyran-4-yl) acetamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} } -? / - (2-hydroxyethyl) acetamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] elil} } -2-hydroxy- / V- (2-hydroxy-ethyl) acefamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy) eyl} } -? / - (2-methoxyeti I) acetamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amine.} Quinazolin-5-l) oxy] efil} } -2-h id roxi -? / - (2-mefoxieti I) acetamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino}. Quinazolin-5-yl) oxy] iiiI} } - / V-prop-2-in-1-ylacetamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino.}. QuinazoIin-5-yl) oxy) efil} } -2-hydroxy -? / - prop-2-in-1-ylacetamide; ? / -. { 2 - [(4- { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} } -2-hydroxy -? / - metylpropanamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmefoxy) phenyl] amino} quinazolin-5-yl) oxy] etl} -N-methyl-tetrahydrofuranyl-2-carboxamide; ? / -. { 2 - [(4- { [3-chloro-4- (pyridin-2-ylmefoxy) phenyl] amino}. Quinazolin-5-i I) oxy] eti} -? /, 1 -di met i I prolinamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy -? /, 2-dimethylpropanamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -1-hydroxy -? / - methylcyclopropanecarboxamide; ? / í-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? /?,? / 2-dimethylglycinamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -3-hydroxy -? /, 2,2-trimethylpropanamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -3-hydroxy -? / - methylpropanamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxyacetamide; ? / í-. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / 2,? / 2-dimethylglycinamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-methoxyacetamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2- (methylsulfonyl) acetamide; ? / -. { 2 - [(4- {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxyacetamide; ? í-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / 2,? / 2-dimethylglycinamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-methoxyacetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] efil} -2- (methylsulfonyl) acetamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / - mef¡lacef amide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-h id roxy- / V-meti I acetamide; ? / í-. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? /?,? / 2,? / 2-trimethylglycinamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-methoxy -? / - methylacetamide; / V-. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmeloxy) phenyl] amino} quinozolin-5-yl) oxy] propyl} -? / - methyl-2- (methylsulfonyl) acetylamide; ? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyrazin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / - methylacetamide; ? / -. { (2R) -2 - [(4- {[3-chloro-4- (1, 3-yiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / - meyilaceiamide; ? / - ((2R) -2- { [4- ( { 3-Chloro-4- (3-fluorobenzyl) oxy] phenyl} amino) quinazolin-5-yl] oxy} propyl ) -? / - methylacetamide; ? / - ((2R) -2- { [4- ( { 3-chloro-4 - [(2-fluorobenzyl) oxy] phenyl} amino) quinazolin-5-yl] oxy}. propyl) -? / - methylacetamide; ? / -. { (1 R) -2 - [(4- {[[[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl ) -2-hydroxy -? / - methylacetamide; ? / -. { (1 R) -2 - [(4- {[[[3-chloro-4- (pyridin-2-ylmehoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl; } -? / - m ethyl aceta mide; ? / -. { (1S) -2 - [(4-. {[[[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. QuinazoIin-5-yl) oxy] -1-methyl 3ttil} -2-hydroxy -? / - methylacecemide; ? / -. { (1 S) -2 - [(4- {([[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl ethyl .} -? / - methylaceaemide;? / -. {(1 S) -2 - [(4- {[[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} -2-methoxy-? / -methylacetamide;? / - { (1 S) -2 - [(4- { [( (3-Chloro-4- (pyridin-2-ylmehoxy) phenyl] amino}. Quinazolin-5-yl) oxy] -1-methyl-ethyl} -2-hydroxyaceiamide;? / -. {(1 S) -2 - [(4- {[[[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-3-ethyl. acetamide; / í.. (1 S) -2 - [(4 - { { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino.}. quinazolin -5-yl) oxy] -1-methyl-3-ethyl} -? / 2,? / 2-dimethylglycinamide;? /? - { (2R) -2 - [(4- - { [3- chloro-4- (pyridin-2-ylmethoxy) phenyl] amino.}. quinazolin-5-yl) oxy] propyl.] -? / 22,? / 2-dimethyglycinamide; (2S) - / -. - [(4- {[[[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] etl.} -2.4-d iihydroxybutanamide; (2R) -? / - { 2 - [(4- { [[[3-clor o-4- (pyridin-2-ylmethoxy) phenyl] amino) quinazolin-5-yl) oxy] eyl} -2,4-dihydroxybufanamide; (2R) -? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4-d hydroxy bufan amide; (2S) -? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4-dih id roxy butan amide; (2R) -? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4-dih id roxy butan amide; (2S) -? / -. { (2S) -2 - [(4- {[3-chloro-4- (pipdin-2-ylmethoxy) phenyl] amino} quinazolin-5-M) oxy] propyl} -2,4-dihydroxybutanamide; (2S) -? / -. { (1 R) -2 - [(4- {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methylethylaryl} -2,4-dihydroxybuanamide; (2R) -? / -. { (1 R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazoIin-5-yl) oxy] -1-methylethyl} -2,4-dihydroxybutanamide; (2R) -? / -. { 2 - [(4- {[3-chloro-4- (1, 3-thiazol-4-ylmeloxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2,4-dihydroxybutanamide; (2S) -? / -. { 2 - [(4- {[3-chloro-4- (1, 3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2,4-dihydroxybutanamide; (2R) -? / -. { (1 R) -2 - [(4- {[3-chloro-4- (1, 3-fiazol-4-ylmeloxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyleryl } -2,4-dihydroxybuanamide; (2S) -? / -. { (1 R) -2 - [(4- {[3-chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl } -2,4-dihydroxybutanamide; ? / - methyl -? / -. { 2 - [(4- {[3-meityyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinozolin-5-yl) oxy] efil} acetylamide; ? / - methyl -? / -. { 2 - [(4- {[3-methyl-4- (1, 3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / - methyl -? / - (2- {[[4- ( { 3-methyl-4 - [(5-methylisoxazol-3-yl) methoxy] phenyl} amino) quinazolin-5-yl. ] oxy} efil) acetylamide; 2-hydroxy -? / - methyl -? / -. { 2 - [(4- {[3-meityl-4- (1, 3-yiazol-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy} ethyl} acetamide; 2-hydroxy -? / -. { 2 - [(4- {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; 2-hydroxy -? / -. { 2 - [(4- {[3-methyl-4- (1, 3-yiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acefamide; / V-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] -1,1-dimethyryl} -2-hydroxyacetamide; 2-hydroxy -? / -. { (2R) -2 - [(4- {[[3-meiyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; 2-hydroxy -? / -. { (2R) -2 - [(4- {[3-methyl-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; ? / - ((2R) -2- { [4- ( { 4 - [(3-Fluorobenzyl) oxy] -3-methylphenyl} amino) quinazolin-5-yl] oxy} propyl ) -2-hydroxyacelamide; 2-hydroxy -? / -. { (2R) -2 - [(4- {[3-methyl-4- (1, 3-thiazol-2-lmetoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; ? / -. { (2R) -2 - [(4- {[3-methyl-4- (pyridin-2-ylmeyoxy) phenyl] amine} quinazolin-5-yl) oxy] propyl} acetamide; ? / -. { (2R) -2 - [(4- {[3-methyl-4- (1, 3-thiazol-4-ylmethoxy) phenyl] amino} quinazoIin-5-yl) oxy] propyl} acetamide; ? / - ((2R) -2- { [4- ( { 4 - [(3-tluorobenzyl) oxy] -3-methylphenyl} amino) quinazoIin-5-yl] oxy} propiI acef amide; N-. { (2R) -2 - [(4- {[3-methyl-4- (1, 3-thiazol-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acefamide; 2-hydroxy- / V-methyl -? / -. { (2R) -2 - [(4- {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetylamide; 2-hydroxy -? / - meyil -? / -. { (2R) -2 - [(4- {[3-meityl-4- (1, 3-yiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; 2-hydroxy- / V-methyl-? / - ((2R) -2- { [4- (. {3-methyl-4 - [(5-methylisoxazoI-3-yl) methoxy] phenyl} amino) quinazolin-5-yl] oxy]. propyl) acetamide; ? / - methyl -? / -. { (1) -1-methyl-2 - [(4. {[[3-mephyl-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetylamide; ? / - meil -? / -. { (1 R) -1-methyl-2 - [(4- {[3-methyl-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / -. { (1) -2 - [(4. {[3-chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazoIin-5-yl) oxy] -1-methyl-ethyl} -2-hydroxy -? / - methylacetamide; 2-hydroxy -? / - methyl-? -. { (1 R) -1-methyl-2 - [(4. {[3-methyl-4- (p.pdin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} acetamide; 2-hydroxy -? / - methyl -? / -. { (1 R) -1-methyl-2 - [(4- {[3-meityl-4- (1, 3-fiazol-4-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) ox ] ethyl} acetamide; ? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -1-hydroxy-β- / -methylcyclopropanecarboxamide; (2S) - / v-. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxy -? / - methylpropanamide; ? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxy -? /, 2-d imeti I propane measure; (2R) -? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxy -? / - mephylpropanamide; (2R) -? / -. { (2R) -2- (4- { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-methoxy -? / - methylpropanamide; methyl-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} methylcarbamate; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? /,? / '- dimethylurea; ? / '- (2-chloroethyl) -? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - meililurea; ? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / '- mefylurea; [((R) -2- { 4- [3-chloro-4- (pyridin-2-ylmethoxy) phenylamino] quinazolin-5-yloxy} propylcarbamoyl) methyl] methylcarbamic tert-butyl ester; and? / í-. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / 2-methylglycinamide; or a pharmaceutically acceptable salt thereof. A particular compound of the invention is, for example, one or more quinazoline derivatives of the formula selected from: 2-hydroxy -? / - methyl -? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy) phenyl} amino) quinazolin-5-yl] oxy} propyl) acetamide; / V-methyl -? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl}. ) quinazoIin-5-yl] oxy}. propyl) acetamide; ? /?,? / 2,? / 2-lrimethyl-N1 - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpridine-3-l) oxy] phenyl.}. amino) quinazolin-5-yl] oxy], propyl) glycinamide; ? / - methyl -? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazoline -5-yl] oxy}. Propyl) -2-pyrrolidin-1-yl-acetamide; ? / - meilyl -? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl.} amino) quinazoline -5-yl] oxy}. Propyl) -2-morpholin-4-ylacetamide; ? / - methyl -? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl.} amino) quinazoline -5-yl] oxy}. Propyl) -2-. { 4-methylpiperazin-1-yl) acetamide; 2-Hydroxy -? / - methyl -? / - ((2S) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl}. amino) quinazolin-5-yl] oxy}. propyl) acetylamide; / V-meityl -? / - ((2S) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazoline -5-yl] oxy}. Propyl) acetamide; ? / - meth-? - ((2S) -2- { [4- ( { 3-methyl-4 - [(6-methyl-pyridin-3-yl) oxy] phenyl} amino) quinazolin-5-yl] oxy .}. propyl) -2-pyrrolidin-1-ylacetamide; (2S) -2,4-dihydroxy-? / - ((2R) -2- { [4- (. {3-Methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazolin-5-yl] oxy}. propyl) butanamide; (2S) -4-bromo-2-hydroxy -? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl.}. amino) quinazolin-5-yl] oxy}. propyl) buanamide; ? / - (2-Chloro-yiyl) -? / '- ((2R) -2- { [4- ( { 3-meyyl-4 - [(6-meilypyridin-3-yl) oxy] phenyl.}. amino) quinazolin-5-yl] oxy}. propyl) urea; 2-hydroxy -? / - methyl -? / - ((1 R) -1-methyl-2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl) amino) quinazolin-5-yl] oxy} ethyl) acetamide; ? / - methyl -? / - ((1 R) -1-methyl-2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazolin-5-yl] oxy} ethyl) acetylamide; 2-hydroxy -? / - methyl -? / - ((1 S) -1-methyl-2 { [4- ( { 3-methyl-4 - [(6-meilypyridin-3-yl) oxy] phenyl.}. amino) quinazolin-5-yl] oxy} ethyl) acetamide; ? / - methyl -? / - ((1 S) -1-methyl-2 { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazolin-5-yl] oxy} ethyl) acetamide; 2-hydroxy -? / - methyl -? / - (2- {[[4- ( {3-methyl-4 - [(6-mephylpyridin-3-yl) oxy] phenyl} amino) quinazoline -5-yl] oxy} ethyl) acetamide; and? / - methyl -? / - (2- {[[4- ( {3-methyl-4 - [(6-methylpyridin-3-M) oxy] phenyl} amino) quinazoIin-5- il] oxy] ethyl) acetamide; or a pharmaceutically acceptable salt thereof. A quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, can be prepared by any process known to be applicable for the preparation of chemically related compounds. Suitable processes include, for example, those illustrated in International Patent Applications WO 96/1 51 1 8, WO 01/94341, WO 03/040108 and WO 03/040109. Such processes, when used to prepare a quinazoline derivative of the formula I, are provided as a further feature of the invention, and are illustrated by the following representative process variants in which, unless stated otherwise, R1 , R2, R3, R4, R4a, R5, R5a, R6, X1, Q1, A, m, and n have any of the meanings defined above in the présenle. The necessary initial materials can be obtained by standard procedures of organic chemistry.

The preparation of such initial materials is described in conjunction with the following representative process variants and within the accompanying Examples. Alternatively, the necessary starting materials are obtained by procedures analogous to those illustrated which are within the ordinary experience of an organic chemist. Process (a) the coupling, conveniently in the presence of a suitable base, of a quinazoline of the formula I I: p wherein R1, R2, R3, R4, R4a, R5, R5a, R6, X1, Q1, m, and n have any of the meanings defined above in the present except that any functional group is proiected if necessary, with an acid carboxylic acid of the formula III, or a reactive derivative thereof: A-COOH III wherein A has any of the meanings defined hereinbefore that any functional group is protected if necessary: o Process (b) for the preparation of those compounds of the formula I wherein X1 is OC (R7) 2, SC (R7) 2 or? / (R7) C (R7) 2, the reaction, conveniently in the presence of a suitable base, of a quinazoline of the Formula IV: IV wherein X1 a is O, S or N (R7) and R1, R2, R3, R4, R4a, R5, R5a, R6, R7, A, and m have any of the meanings defined herein above except that any functional group is protected if necessary, with a compound of the formula V or a salt thereof: Q1-C (R7) 2-L1 V where L1 is a suitable displaceable group and Q1 and R7 have any of the meanings defined above in the present except that any functional group is protected if necessary; Process (c) for the preparation of those compounds of formula I wherein A is R14 and R14 is NHR17 or Q3-X5- (wherein R17 and Q3 has any of the meanings defined hereinbefore and X5 is NH), the coupling of a quinazoline of the formula II as defined above with an isocyanate of the formula I: A-NCO Illa wherein A is R14 as previously defined in this section except that any functional group is protected if necessary; Process (d) the reaction of a quinazoline of the formula I I wherein R6 is hydrogen: p wherein R1, R2, R3, R4, R4a, R5, R5a, X1, Q1, m and n have any of the meanings defined herein above except that any functional group is protected if necessary, with α-hydroxy -? - butyrolactone (for example (S) - (-) - α-hydroxy-β-butyrolactone or (R) - (+) - a-hydroxy -? - butyrolactone) where any functional group is professed if necessary; Process for the coupling of a quinazoline of formula VI: VI wherein R1, R4, R4a, R5, R5a, R6, A and m have any of the meanings defined herein above except that any functional group is protected if necessary, with a compound of the formula lb: llb wherein R2, R3, X1, Q1 and n have any of the meanings defined herein above except that any functional group is protected if necessary; Process (f) for the preparation of those compounds of the formula I wherein X 1 is O and Q 1 is 2-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl. 2-pyrazinyl or 3-pyridazinyl, the reaction, conveniently in the presence of a suitable base and a suitable catalyst, of a quinazoline of the formula Vi: vp wherein R 1, R 2, R 3, R 4, R a, R 5, R 5 a, R 6, A, m and n have any of the meanings defined herein above except that any functional group is protected if necessary, with 2-bromopyridine, -bromopyridine, 2-chloropyrimidine, 4-chloropyrimidine, 2-chloropyrazine or 3-chloropyridazine; Process (q) for the preparation of those compounds of the formula I wherein A is Z- (CR12R13) P-, wherein Z is NR16R17, the reaction, conveniently in the presence of a suitable base, of a quinazoline of the Formula VI II: Vffl where L1 is a suitable displaceable group and R1, R2, R3, R4, R4a, R5, R5a, R6, R12, R13, X1, Q1, m, n and p have any of the meanings defined herein above except that any functional group is protected if necessary, with a compound of the formula IXa, or a reactive derivative thereof: H-NR1 6R17 IXa wherein R16 and R17 have any of the meanings defined herein above except that any functional group is protected if required; and then, if necessary: (i) converting a quinazoline derivative of the formula I into another quinazoline derivative of the formula I; (ii) remove any protective group that is present by conventional means; (iii) forming a pharmaceutically acceptable salt. The specific conditions of the above reactions are as follows: Process (a) The coupling reaction is conveniently carried out in the presence of a suitable coupling agent, such as carbodiimide, or a suitable peptide coupling agent, for example O- (7-azabenzotriazol-1-yl) - N, N, N ', N'-Iemeramide hexafluoro-phosphate (HATU) or a carbodiimide such as optionally in the presence of a catalyst such as dimethylaminopyridine or 4-pyrrolidinopyridine. The coupling reaction is conveniently carried out in the presence of a suitable base. A proper base is, for example, an organic amine base such as, for example, pyridine, 2,6-lutidine, collidine, 4-dimethylaminopyridine, ithylamine, di-isopropylethylamine, JN-methylmorpholine or diazabicyclo [5.4.0] undec-7-ene , or, for example, a carbonation of alkaline or alkali earth mefal, for example, sodium carbonate, potassium carbonate, cesium carbonate, calcium carbonate. The reaction is conveniently carried out in the presence of a suitable inert solvent or diluent, for example a ester such as ethyl acetate, a halogenated solvent such as methylene chloride, chloroform or carbon tetrachloride, an ether such as tetrahydrofuran or , 4-dioxan, an aromatic solvent such as toluene, or a dipolar aliphatic solvent such as JN, J __- d¡melylformamide, JN. N-dimethylacetamide, JN-methylpyrrolidin-2-one or dimethylsulfoxide. The reaction is conveniently carried out at a temperature in the range, for example, from 0 to 120 ° C, conveniently at or near room temperature. By the term "reactive derivative" of the carboxylic acid of the formula I I I means a carboxylic acid derivative which will react with the quinazoline of the formula I I to give the corresponding amide. A suitable reactive derivative of a carboxylic acid of the formula I I I is, for example, an acyl halide, for example an acyl chloride formed by the reaction of the acid and an inorganic acid chloride, for example thionyl chloride; a mixed anhydride, for example an anhydride formed by the reaction of the acid and a chloroform such as isobutyl chloroformoate; an active ester, for example an ester formed by the reaction of the acid and a phenol such as pentafluorophenol, a ester such as penofluorophenyl-rifluoroacetate or an alcohol such as melanol, eneol, isopropanol, butanol or JN-hydroxybenzotriazole; an acyl azide, for example an azide formed by the reaction of the acid and azide such as diphenylphosphoryl azide; an acyl cyanide, for example a cyanide formed by the reaction of an acid and a cyanide such as diethylphosphoryl cyanide; or an acetoxy acetylchloride. The reaction of such reactive derivatives of carboxylic acid with amines (such as a compound of formula II) is well known in the maigery, for example it can be reacted in the presence of a base, such as those described above, and in a suitable solvency. , such as those described above. The reaction can be conveniently carried out at a temperature as described above. Preparation of Initial Processes for the Process (a) The compounds of the formula I I (and reactive derivatives thereof) are commercially available compounds or are known in the literature, or can be prepared by standard processes known in the art. The quinazoline of the formula I I can be obtained by conventional methods. For example, as illustrated in Reaction Scheme 1: IW Reaction Scheme 1 where L2 and L3 are suitable displaceable groups, provided that L3 is more labile than L2, and R1, R2, R3, R4, R4a, R5, R5a, R6, X1, Q1, m, and n have any of the meanings defined hereinbefore except that any functional group is protected if necessary during the reaction set forth above, such protective group (s) are removed if necessary to an appropriate step in Reaction Scheme 1 For example, instead of using the compound of formula I id in step (ii) of Reaction Scheme 1, the compound id (including a protecting group) could be used: lid1 followed by withdrawal from the protection group, by an appropriate method known to a person experienced in maieria. A suitable displaceable group L2 is, for example, halogen or a sulphonyloxy group, for example fluoro, chloro, methylsulfonyloxy or toluene-4-sulfonyloxy group, particularly fluoro. A suitable displaceable group L2 is, for example, halogen (such as fluoro or chloro) or an alkoxy, aryloxy, mercapto, alkylthio, arylthio, alkylsulfinyl, arylsulphyl, alkylsulfonyl, arylsulphonyl, alkylsulfonylxy or arylsulphonylxy group, for example a chloro group, bromine, methoxy, phenoxy, pentafluorophenoxy, methylthio, methanesulfonyl, methanesulfonylxy or toluene-4-sulfonyloxy. Preferably L2 and L3 are both halogen, for example L2 is fluoro and L3 is chloro. Notes for Reaction Scheme 1: Step (i) The reaction is conveniently carried out in the presence of an acid. Suitable acids include, for example, hydrogen chloride gas (suitably dissolved in a suitable inert solvent such as diethyl ether or dioxane) or hydrochloric acid. Most preferably the quinazoline derivative of the formula Ha, wherein L3 is halogen (for example chlorine), can be reacted with the compound of the formula lb in the absence of an acid or a base. In this reaction shift of the leaving group of halogen L3 resulted in the formation of H L3 acid in situ and the autocatalysis of the reaction. Alternatively, the reaction of the quinazoline derivative of the formula lal with the compound of the formula 1 lb can be carried out in the presence of a suitable base. A suitable base is, for example, an organic amine base such as, for example, pyridine, 2,6-lutidine, collider, 4-dimethylaminopyridine, triethylamine, diisopropylethylamine, JN-methylmorpholine or diazabicyclo [5.4.0] undec-7. -nene, or, for example, an alkali metal or alkali metal carbonate, for example, sodium carbonate, pofasium carbonate, cesium carbonate, calcium carbonate, or, for example, an alkali metal hydride, for example sodium hydride. The above reactions are conveniently carried out in the presence of a suitable inert solvent or diluent, for example, an alcohol or an ester such as methanol, ethylene, isopropanol or ethyl ether, a halogenated solvent such as methylene chloride, chloroform or carbon tetrachloride, an ial ether such as fetrahydrofuran or 1,4-dioxan, an aromatic solvent such as toluene, or a dipolar aprotic solvent such as JN, JN-dimethylformamide,, JN-d-methylacefamide, JN-methylpyrrolidin-2 -one or dimethylsulfoxide. The above reactions are conveniently carried out at a temperature in the range, for example, 0 to 250 ° C, conveniently in the range of 40 to 80 ° C, preferably at or near the reflux temperature of the solvent when used . Step (ii) The reaction of a quinazoline of the formula Ie and the alcohol of the formula I id is suitably carried out in the presence of a suitable base, for example a strong non-nucleophilic base such as an alkali metal hydride, for example sodium hydride, or an alkali metal amide, for example lithium diisopropylamide (LDA). The reaction of the quinazoline of the formula Ie and the alcohol of the formula I id is conveniently carried out in the presence of a suitable inert solvent or diluent., for example a halogenated solvent such as methylene chloride, chloroform or carbon tetrachloride, an ether such as tetrahydrofuran or 1,4-dioxan, an aromatic solvent such as toluene, or a dipolar aprotic solvent such as JN, JN-dimet Iformamide, JN. JN-dimethylacetamide, JN-methylpyridin-2-one or dimethylsulfoxide. The reaction is conveniently carried out at a temperature in the range of, for example, 1 0 to 250 ° C, preferably in the range of 40 to 150 ° C. Conveniently, this reaction can also be performed by heating the reagents in a sealed container using a suitable heating apparatus such as a microwave heater. Conveniently, the reaction of a quinazoline of the formula Ie and the alcohol of the formula I id is carried out in the presence of a suitable calychator, for example, a crown emulsion, such as 15-crown-5. Plain Materials for Reaction Scheme 1 Quinazoline of the formula Ha can be obtained using conventional methods, for example, when m is 0, L2 is fluoro and L3 is halogen (eg, chlorine), 5-fluoro-3,4- Dihydroquinazolin-4-one can be reacted with a suitable halogenating agent such as thionyl chloride, phosphoryl chloride or a mixture of carbon tetrachloride and triphenylphosphine. The starting material 5-fluoro-3,4-dihydroquinazoline is commercially available or can be prepared using conventional methods, for example as described in J. Org. Chem. , 1 952, 17, 164-1 76. Compounds of the formula I lb are commercially available compounds or are known in the literature, or can be prepared by standard processes known in the art. For example, the compound of the formula l lb in which R2 is hydrogen and wherein X1 is O, S, SO, SO2, N (R7), OC (R7) 2, SC (R7) 2 or N (R7) C (R7) 2 can be prepared according to Reaction Scheme 2: Reaction Scheme 2 wherein L4 is a suitable displaceable group as defined herein above (for example, halogen such as chlorine) and Q1, X1, R3 and n are as defined in the foregoing, except any functional group is protected if necessary, and any proiector group that is present in Reaction Scheme 2 is removed if necessary to an appropriate stage of Reaction Scheme 2 by conventional means. Notes for Reaction Scheme 2 Step (i): Compounds of the formula HX1Q1 are commercially available, or are known in the literature, or can be prepared using processes well known in the art. For example, compounds of the formula Q 1 CH 2 OH can be prepared using known methods, for example, by reduction of the corresponding ester of the formula Q 1 COOR, wherein R is, for example alkyl (1-6C), or benzyl, with an agent suitable reducing agent, for example, sodium borohydride, followed by ester hydrolysis. The reaction in step (i) is conveniently carried out in the presence of a suitable base and in the presence of a suitable inert diluent or solvent. The suitable reaction conditions, solvents and bases to be used in step (i) are analogous to those used in Process (b) described below. Step (ii): The reduction of the nitro group in step (ii) can be carried out under standard conditions. For example, by cagelitic hydrogenation on a platinum / carbon, palladium / carbon or nickel caffler, a metal oxide such as iron, thifanium chloride, sodium II or indium chloride, or treatment with another suitable reducing agent such as dithionium sodium. Compounds of the formula I lb wherein X 1 is OC (R 7) 2, SC (R 7) 2 or N (R 7) C (R 7) 2, for example, can be prepared according to Reaction Scheme 3: Reaction Scheme 3 wherein L1 is a suitable leaving group as defined herein below in relation to Process (b), X1 a is as defined above in the present in Process (b), and R3, R7 , Q1, X1 and are not as defined herein except that any functional group is protected if necessary, and any protecting group that is present in Reaction Scheme 3 is removed if necessary at an appropriate stage of the Reaction Scheme. 3 by conventional means. Notes for the Reaction Scheme 3 Stage (i): Conditions analogous to those used in the Process (b) Eíapa (ii): Conditions analogous to those used in the Reaction Scheme 2. Other suitable methods for preparing the compounds of the formula l lb are described in for example, WO 03/0401 08 and as illustrated by the examples in the present. Compounds of formula 11b wherein X 1 is OC (R 7) 2 may also be prepared by coupling the appropriate initial nitro phenol in Reaction Scheme 3 (X 1 to H is OH) with a compound of the formula Q 1 C (R 7) 2 OH, conveniently in the presence of a suitable dehydrating agent. A dehydrating agent is, for example, a carbodiimide reagent such as dicyclohexylcarbodiimide or 1- (3-dimethylaminopropyl) -3-efilcarbodiimide or a mixture of an azo compound such as diethyl and di-éri-butyl azodicarboxylafo and a phosphine such as triphenylphosphine. The reaction is conveniently carried out in the presence of a suitable inert solvent or diluent, for example, a halogenated solveny such as methylene chloride, chloroform or carbon tetrachloride and at a temperature in the range, for example, 0 to 150 °. C, preferably at or near room temperature. The alcohols of the formula I id used in Reaction Scheme 1 are commercially available compounds or are known in the literature, or can be prepared by standard processes known in the maigery. For example, alcohols of the formula I id can be prepared according to Reaction Scheme 4: lid 'Reaction Scheme 4 where Pg is a suitable amine protecting group such as ally, and R4, R4a, R5, R5a and R6 are as defined herein above. Notes for Reaction Scheme 4 EIApa (i): The ring and coupling aberration reaction is conveniently carried out in the presence of a suitable mehal catalyst such as ytterbium trifluoromethanesulfonate (I I I). The reaction is carried out suitably in the presence of an inert solvent such as dioxane. The reaction is carried out preferably at an elevated temperature, for example from 50 to approximately 150 ° C. Step (i): The Pg protein group can be removed using conventional methods, for example, when Pg is an allyl group by metalized separation of metal. A suitable catalyst is, for example, chlorotris (triphenylphosphine) rhodium (I). As it was previously mentioned, in modalities, the alcohol of formula I 'in Reaction Scheme 4 can be used directly in Process (a) (or in the preparation of intermediary compounds used in process (b) described down). In this embodiment the amine protecting group, Pg, can be removed at a convenient stage in the process of coupling the acid of the formula II I. The quinazoline of the formula II can be obtained alternatively from a conventional procedure, for example, as illusive in Reaction Scheme 1a: Reaction Scheme 1a wherein L1 and L2 are suitable displaceable groups and R1, R2, R3, R4, R4a, R5, R5a, R6, X1, Q1, m, and n have any of the meanings defined herein above except that any The functional group is protected if necessary during the reaction described above, if the group (s) profecfor (s) is removed if necessary in a suitable step in Reaction Scheme 1a.

A suitable displaceable group L2 is for example a halogen or a sulphonyloxy group, for example, a fluoro, chloro, meilylsulfonyloxy or toluene-4-sulfonyloxy group, particularly fluoro. Preferably L2 is halogen, for example L2 is fluoro. A suitable displaceable group L1 in the compound of the formula He 'is, for example, a halogen or a sulfonylxy group, for example, a fluoro, chloro, methylsulfonylxy or toluene-4-sulfonyloxy group. A particular group L1 is fluoro, chloro, or methylsulfonylxy, particularly chloro. Notes for Reaction Scheme 1 a: Stage (i): Conditions analogous to those used in stage (ii) of Reaction Scheme 1. Step (ii): Conducted by using an appropriate conversion reaction. For example, when L1 is chlorine, step (ii) is conducted using an appropriate chlorinating agent, for example, thionyl chloride. Step (iii): The reaction of the compound of the formula He 'with the amine of the formula Ilf can be conveniently carried out in the presence of a suitable base. A suitable base is, for example, an organic amine base such as pyridine, 2,6-lutidine, collidine, 4-dimethylaminopyridine, urea-amylamine, diisopropylethylamine, JN-methylmorpholine or diazabicyclo [5.4.0] undec-7-ene, or a carbonation of alkaline earth metal or alkali as sodium carbonate, pofasium carbonate, cesium carbonate, calcium carbonate, or an alkaline metal hydride such as sodium hydride.

Alternately, the reaction can use an excess of the amine of formula I, instead of the appropriate base mentioned above. If necessary, the reaction can be conveniently carried out in the presence of a suitable catalyst, for example, iorabutylammonium iodide. The reaction of the compound of the formula I 'and the amine of the formula I is conveniently carried out in the presence of a suitable inert solvent or diluent, for example an ether such as tetrahydrofuran or 1,4-dioxane, a solvent aromatic such as uenole, or a dipolar aprolic solution such as JN, JN-dimethylarformamide, JN.JN-dimethylacetamide, N-methylpyrrolidin-2-one or dimethylsulfoxide. The reaction is conveniently carried out at an hour in the range of, for example, 25 to 150 ° C, conveniently about 1 00 ° C. Useful Materials for Reaction Scheme 1a Compounds of formula I can be prepared using conventional procedures, for example, as discussed above in relation to Reaction Scheme 1. Compounds of formulas He and I are commercially available compounds or are known in the literature, or can be prepared by standard processes known in the art. Process (b) A suitable displaceable group L 1 in the compound of the formula V is for example a halogen or a sulphonyl group, for example a fluoro, chloro, methylsulphonyloxy or toluene-4-sulfonyloxy group.

A particular group L1 is fluoro, chloro or methylsulfonylxi. The reaction of the formula of the formula IV with the compound of the formula V is conveniently carried out in the presence of a suitable base. Suitable bases include, for example, an organic amine base such as, for example, pyridine, 2,6-lutidine, collidine, 4-dimethylaminopyridine, triethylamine, diisopropylethylamine, JN-methylmorpholine or diazabicyclo [5.4.0] undec-7-ene. , or, for example, an alkali or alkali earth metal carbonate, for example, sodium carbonate, pofasium carbonate, cesium carbonate, calcium carbonate or, for example, an alkali metal hydride, eg, sodium hydride . A parficular base is an alkali earth or alkali metal carbonate, for example, potassium carbonate. The reaction of the quinazoline of the formula IV and the compound of the formula V is conveniently carried out in the presence of a suitable inert solvent or diluted, for example, with a halogenated solvent such as methylene chloride, chloroform or carbon tetrachloride, an ether such as tetrahydrofuran or 1,4-dioxane, an aromatic solvent such as toluene, or a dipolar aprotic solvent such as JN, JN-dimethylformamide, JN, JN-dimethylacetamide, JN-methylpyridinidin-2-one or dimethisulfoxide. The reaction is conveniently carried out at a temperature in the range of, for example, 25 to 100 ° C, conveniently at or near room temperature. The reaction of the quinazoline of the formula IV and the compound of the formula V is conveniently carried out in the presence of a suitable catalyst, for example, a crown ether such as 18-crown-6. Preparation of Initial Processes for the Process (b) The compounds of formula V are commercially available compounds or are known in the literature, or can be prepared by standard processes known in the art. The quinazoline of formula IV can be prepared using conventional methods, for example, when X1 a is O, according to Reaction Scheme 5: Reaction Scheme 5 wherein L2 and L3 are suitable displaceable groups, provided that La is more labile than L2, as defined above in relation to Reaction Scheme 1, and R1, R2, R3, R4, R4a, R5a, R6 , A, m and n have any of the meanings defined hereinbefore except that any functional group is protected if necessary during the above reaction, the protecting group (s) is removed if necessary in a suitable step in the Reaction Scheme 5. Noahs for Reaction Scheme 5: Eíapa (i): Conditions analogous to those used in stage (i) in the Reaction Scheme 1. Stage (ii): Conditions analogous to those used in stage (ii) in Reaction Scheme 1. Stage (iii): Conditions analogous to those used in Process (a) or Process (c). As discussed in relation to Process (a), the compound of the formula I I can be used as the free acid as represented in Reaction Scheme 5 or as a reactive derivative of the compound of the formula I I I. Suitable reactive derivatives of the compound of formula III are described in relation to Process (a) above. Preparation of Initial Guidelines for the Reaction Scheme 5 The compounds of the formulas Ha and l can be obfened by conventional procedures, as discussed above. Anilines of the formula IVa are commercially available compounds or are known in the literature, or can be prepared by standard processes known in the art. Process (c) The reaction of a compound of formula ll with an isocyanate of formula I is conveniently carried out in the presence of a suitable inert solvent or diluent, for example, an ester such as ethyl acetate, a solvenle halogenated lal as methylene chloride, chloroform or carbon tetrachloride, an ether such as tetrahydrofuran or 1,4-dioxan, an aromatic solvent such as toluene, or a dipolar aprotic solvent such as JN.JN-dimethylformamide, JN.JN- dimethylacetamide, JN-methylpyrrolidin-2-one and dimethisulfoxide. The reaction is conveniently carried out at a temperature in the range, for example, from 0 to 50 ° C. Preparation of Inicidal Materials for Process (c) The quinazoline of formula I I can be obtained by conventional procedures, as discussed above. The compounds of formula I are commercially available compounds or are known in the art, or can be prepared by standard processes known in the art. Process (d) The reaction of the compound of the formula I I a-hydroxy-γ-butyrolactone is conveniently carried out in the presence of a suitable inert solvent or dilute, for example, xylene, uenole or dichlorobenzene (particularly xylene). The reaction is conveniently carried out at a temperature in the range, for example, from 1 00 to 180 ° C. Preparation of Initial Materials for the Process (d) The quinazoline of the formula I I can be obtained by conventional procedures, as discussed above. The α-hydroxy-γ-butyrolactones are commercially available compounds or are known in the literature, or can be prepared by standard processes known in the maigery. Process (e) The reaction of the compounds of formula VI and formula Ib is conveniently carried out using conditions analogous to those described above for Step (i) of Reaction Scheme 1. Quinazoline of formula VI can obtained by conventional procedures, as outlined above. The compounds of formula I lb can be obtained by conventional procedures, as discussed above. Process (f) A catalyst suitable for the reaction of a quinazoline of the formula Vi 1 and 2-chloropyrimidine, 4-chloropyrimidine, 2-chloropyrazine or 3-chloropyridazine is, for example, a crown ether such as 18-crown-6. A suitable catalyst for the reaction of a quinazoline of the formula Vi 1 and 2-bromopyridine or 4-bromopyridine is a palladium catalyst, for example, a catalyst formed in situ by the reaction of bis (dibenzylideneacetone) palladium and 9,9-dimethylamino-4,5-bis (diphenylphosphino) xanthene. The reaction is conveniently carried out in the presence of a suitable base. A suitable base is, for example, an alkali or alkali earth metal carbonate, for example, sodium carbonate, potassium carbonate, cesium carbonate or calcium carbonate. The reaction is conveniently carried out in a suitable inert solvent or diluent, for example an ether such as tetrahydrofuran or 1,4-dioxane, or a dipolar aprotic solvent such as acetonitrile. Suitably the reaction is carried out at a temperature of, for example, 0 to 1 80 ° C, particularly 20 ° C at the reflux temperature of the solvent / diluent. Conveniently, the reaction can also be carried out by heating the reagents in a sealed container using a suitable heating apparatus such as a microwave heater. Preparation of Initial Materials for the Process (f) The quinazoline of the formula VI can be obtained by conventional procedures, as discussed above. The reagents of 2-bromopyridine, 4-bromopyridine, 2-chloropyrimidine, 4-chloropyrimidine, 2-chloropyrazine and 3-chloropyridazine are commercially available compounds or are known in the literature, or can be prepared by processes known in the art.

Process (g) The reaction of the compound of formula VI H and the amine of formula IXa is conveniently carried out using conditions analogous to those used in step (iii) in Reaction Scheme 1a.

Preparation of Inicidal Materials for the Process (g) The quinazoline of the formula VI H can be obtained by conventional procedures, as it was brought up. The amines of the formula IXa are commercially available compounds or are known in the literature, or can be prepared by standard processes known in the art. The quinazoline derivative of the formula I can be obtained from the above processes in the form of the free base or alternatively it can be obtained in the form of a salt, such as an acid addition salt. When it is desired to obtain the free base of a salt of the compound of the formula I, the salt may be treated with a suitable base, for example, an alkali metal or alkali metal hydroxide or carbonate, for example, sodium carbonate, carbonate poiasium, calcium carbonate, sodium hydroxide or potassium hydroxide, or by ammonia treatment, for example using a solution of melanic ammonia fal as 7N ammonia in meianol. The protecting groups used in the above processes may in general be chosen from any of the groups described in the text or known by the chemical expert as appropriate for the projection of the group in question and may be introduced by conventional methods. The protecting groups can be removed by any conventional method as described in the literature or known by the experienced chemist as appropriate for the removal of the protecting group in question, such methods being chosen to effect the removal of the protecting group with minimal disturbance of groups in any part in the molecule. Specific examples of protecting groups are given below for convenience, in which "lower", as in, for example, lower alkyl, means that the group to which it is applied preferably has 1 to 4 carbon atoms. It will be understood that these examples are not exhaustive. Although specific examples of methods for removal of protecting groups are given below these are similarly not exhaustive. The use of protecting groups and deprotection methods not specifically mentioned are, of course, within the scope of the invention. A carboxy-protecting group may be the residue of an ester-forming aliphatic or arylaliphatic alcohol or of an ester-forming silanol (said alcohol or silanol preferably containing 1 to 20 carbon atoms). Examples of carboxy-protecting groups include straight and branched chain alkyl groups (1 -12 C) (eg, isopropyl, and tert-butyl); lower alkoxy-lower alkyl groups (for example methoxymethyl, ethoxymethyl and isobuoxymethyl); lower acyloxy-lower alkyl groups (for example acetoxymethyl, propionyloxymethyl, buyryloxymethyl and pivaloyloxymethyl); lower alkoxycarbonyloxy-lower alkyl groups (for example 1-methoxycarbonyloxy-1-yl-ethoxycarbonyloxyethyl); aryl-lower alkyl groups (for example benzyl, 4-methoxybenzyl, 2-nitrobenzyl, 4-nitrobenzyl, benzhydryl and eftalidyl); tri (lower alkyl) silyl groups (for example trimethylsilyl and tert-butyidylmethylsilyl); tri (lower alkyl) silyl-lower alkyl groups (for example trimethylsilylethyl); alkenyl (2-6C) groups (for example allyl). Particularly suitable methods for removal of carboxyl protecting groups include for example enzymatically catalyzed separation of metal, base or acid. Examples of hydroxy protecting groups include lower alkyl groups (for example tert-butyl), lower alkenyl groups (for example allyl); lower alkanoyl groups (for example acetyl); lower alkoxycarbonyl groups (for example, rt-budoxycarbonyl); lower alkenyloxycarbonyl groups (for example allyloxycarbonyl); lower α-alkoxycarbonyl groups (for example benzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl and 4-nitrobenzyloxycarbonyl); tri (lower alkyl) silyl groups (for example trimethylsilyl and terf-buildyldsilylsilyl) and aryl-lower alkyl (for example benzyl). Examples of amino protecting groups include formyl, aryl-lower alkyl groups (for example benzyl and substituted benzyl, 4-methoxybenzyl, 2-nitrobenzyl and 2,4-dimethoxybenzyl, and triphenylmethyl); lower alkenyl groups (for example allyl); di-4-anisylmethyl and furylmethyl groups; alkoxycarbonyl groups (for example tert-bufoxicarbonyl); lower alkenyloxycarbonyl (for example allyloxycarbonyl); aryl-lower alkoxycarbonyl (for example benzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl and 4-nitrobenzyloxycarbonyl); lower alkanoyloxyalkyl groups (for example pivaloyloxymethyl); trialkylsilyl (for example trimethylsilyl and tert-butyidylmethylsilyl); alkylidene (for example methylidene) and benzylidene and substituted benzylidene groups.

Appropriate methods for the removal of amino and hydroxy protecting groups include, for example, enzymatically catalyzed hydrolysis of metal, base or acid for groups such as 2-nitrobenzyloxycarbonyl and allyl, hydrogenation for groups such as benzyl and photolytically for groups such as 2- nifrobenzyloxycarboniI. For example, a tert-butoxycarbonyl protecting group can be removed from an amino group by an acidic hydrolysis using trifluoroacetic acid. The reader refers to Advanced Organic Chemistry, 4th Edition, by J. March, published by John Wiley & Sons 1 992, for general guidance under reaction conditions and reagents and to Protective Groups in Organic Synthesis, 2nd Edition, by T. Green et al. , also published by John Wiley & They are, for general guidance in protective groups. It will be appreciated that certain of the various ring substituents in the compounds of the present invention can be produced by standard aromatic sub-affinity reactions or generated by modifications of the conventional functional group either before or immediately after the processes mentioned above, and as such are included in the aspect of the process of the invention, such reactions and modifications include, for example, introduction of a substituent by means of an aromatic substitution reaction, reduction of substituents, alkylation of substituents and oxidation of substituents. The reactants and reaction conditions for such processes are well known in the chemical field. Particular examples of aromatic substitution reactions include the inroduction of a nitro group using concentrated nitric acid, the introduction of an acyl group using, for example, an acyl halide and Lewis acid (eg as aluminum fluoride) under Friedel Crafts conditions; the inroduction of an alkyl group using a halide alkyl and Lewis acid (such as aluminum chloride) under Friedel Crafts conditions; and the introduction of a halogen group. When a pharmaceutically acceptable salt of a quinazoline derivative of the formula I is required, for example an acid addition salt, it can be obtained by, for example, reacting said quinazoline derivative with a suitable acid using a conventional procedure. As mentioned above in the presence of the compounds according to the present invention, one or more chiral centers can be formed and therefore can exist as stereoisomers (for example, when R 4 is alkyl and R 4a is hydrogen). The stereoisomers can be separated using conventional techniques, for example, chromatography or fractional chrysphalization. The enantiomers can be isolated by separation of a racemate, eg by fractional crystallization, resolution or HPLC. The diastereoisomers can be isolated by separation by virtue of the different physical properties of the diastereoisomers, for example, by fractional crystallization, HPLC or flash chromatography. Alternatively, particular stereoisomers can be made by chiral synthesis of chiral starting materials under conditions that will not cause racemization or epimerization, or by derivatization, with a chiral agent. When a specific stereoisomer is isolated it is suitably isolated substantially free of other isomers, for example, containing less than 20%, particularly less than 10% and more particularly less than 5% by weight of the other stereoisomers. In the lower section relating to the preparation of the quinazoline derivative of the formula I, the term "inert solvent" refers to a solvent that does not react with the initial materials, reagents, intermediate compounds or products in a manner that adversely affects the production of the desired product. Experts in the field will appreciate that, in order to obey the compounds of the invention in an alirnative way and in some occasions, more convenient, the individual steps of the process mentioned hereinbefore can be performed in a different order, and / or the individual reactions can be performed at a different stage in the total route (i.e., chemical transformations can be performed on different intermediary compounds to those associated in the present before with a parficular reaction). Intermediate composite screens used in the process described above are new and form an additional feature of the present invention. According to the foregoing, a compound of formula IV as defined herein, or a salt thereof, is provided. The intermediate compound can be in the form of an intermediate compound salt. Such salts do not need to be a pharmaceutically acceptable salt. For example, it may be useful to prepare an intermediate compound in the form of a pharmaceutically unacceptable salt if, for example, such salts are useful in the manufacture of a compound of formula I. Biological Analysis The inhibitory activities of the compounds are assessed in non-cell-based protein tyrosine kinase assays as well as in cell-based proliferation assays before their in vitro activity were assessed in Xenograft studies. a) Protein Tyrosine Kinase Phosphorylation Assays This test measures the ability of a test compound to inhibit the phosphorylation of a tyrosine-containing polypeptide substrate by an erb receptor tyrosine kinase enzyme. The recombinant intracellular fragments of EGFR, erbB2 and erbB4 (accession numbers X00588, X03363 and L07868 respectively) are cloned and expressed in the baculovirus / Sf21 system. The lysates are prepared from these cells by treatment with cold lysis regulator (20mM N-2-hydroxyethylpiperazine-N'-2-phenyanosulfonic acid (HEPES) pH7.5, 150 mM NaCl, 1 0% glycerol, 1% Triton X- 1 00, 1.5 mM MgCl2, 1 mM Ethylene glycol-bis (ß-aminoethyl) acid, N 'N', N'-tetraacetic acid (EGTA), plus protease inhibitors and then cleaved by centrifugation.

Recombinant protein kinase activity is deferred by its ability to phosphorylate a synthetic peptide (made from a random copolymer of glutamic acid, alanine and tyrosine in the ratio of 6: 3: 1). Specifically, the Maxisorb ™ 96-well immunoplates are coated with synthetic peptide (0.2 μg of peptide in 200 μl phosphate-buffered saline (PBS) and incubated at 4 ° C overnight). The plates are rinsed in 50 mM H EPES pH 7.4 at room temperature to remove any excess unbound synthetic peptide. EGFR or erbB2 activities are assessed by incubation in peptide-coated plates for 20 minutes at room temperature in 100 mM HEPES pH 7.4 at room temperature, adenosine triphosphate (ATP) at Km concentration for the respective enzyme, 1.0 mM MnCl2, 0 1 mM Na3VO4, 0.2 mM DL-dithiothreitol (DTT), 0.1% Triton X-100 with test compound in DMSO (final concentration 2.5%). The reactions are terminated by the removal of the liquid components of the assay followed by rinsing the plates with PBS-T (phosphate-regulated salt with 0.5% Tween 20). The immobilized phospho-peptide product of the reaction is detected by immunological methods. First, plates are incubated for 90 minutes at room temperature with primary anti-phosphotyrosine antibodies originating in the root (4G10 from Upsfaie Biotechnology). Following extensive rinsing, the plates are treated with sheep anti-mouse secondary antibody conjugated with Horseradish Peroxidase (H RP) (NXA931 from Amersham) for 60 minutes at ambient temperature. After further rinsing, the RP H acfivity in each plate cavity is measured colorimically by using salt crystals 22'-Azino-di- [3-eylbenzfiazoline sulfonate (6)] diammonium (ABTS ™ from Roche) as a subframe . The quantification of color development and thus enzyme activity is achieved by measuring absorbance at 405nm in a TermoMax microplate reader from Molecular Devices. The inhibition of kinase for a given compound is expressed as an IC50 value. This is determined by calculating the concentration of compound that is required to give 50% inhibition of phosphorylation in this assay. The phosphorylation range is calculated from the positive control values (vehicle plus ATP) and negative (vehicle minus ATP). b) KBFR cell proliferation assay driven by EGFR This assay measures the ability of a test compound to inhibit the proliferation of KB cells (human naso-pharyngeal carcinoma obtained from the American Type Culture Collection (ATCC)). The KB cells are cultured in Dulbecco's Modified Eagle's Medium (DMEM) containing 1% of fetal bovine serum, 2 mM of glutamine and non-essential amino acids at 37 ° C in a 7.5% CO2 air incubator. The cells are harvested from the reserve flasks using ipsin / ethylaminodiatetraacetic acid (EDTA). The cell density is measured using a hemocytometer and the viability is calculated using blue fripan solution before sowing at a density of 1.25x103 cells per well of a 96-well plate in DMEM containing 2.5% serum in carlon strips, 1 mM of glufamine and non-essential amino acids at 37 ° C in 7.5% CO2 and allowed to stand for 4 hours. After adhesion to the plate, the cells were brought with or without EGF (final concentration of 1 ng / ml) and with or without compound in a range of concentrations in dimethylsulfoxide (DMSO) (0.1% final) before incubation by 4 days. After the incubation period, cell numbers are determined by the addition of 50 μl of 3- (4,5-Dimethylthiazol-2-yl) -2,5-diphenyl-tert-amolol (MTT) bromide (5 mg / ml stock) ) for 2 hours. The MTT solution is then uncovered, the plate is capped dry and the cells are dissolved in the addition of 1000 μl of DMSO. The absorbance of the solubilized cells is read at 240 nm using a Molecular ThermoMax microplate reader Devices. Proliferation inhibition is expressed as a pc50 value. This is determined by calculating the concentration of compound that is required to give 50% inhibition of proliferation. The proliferation range is calculated from the negative (vehicle plus EGF) and negative (vehicle minus EGF) control values. c) Cellular EGFR phosphorylation assay This assay measures the ability of a test compound to inhibit EGFR phosphorylation in KB cells (human nasopharyngeal carcinoma obtained from the American Type Culíivo Collection (ATCC).

The KB cells are cultured in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum, 2 mM glutamine and essential amino acids at 37 ° C in 7.5% CO2 air incubator. Cells were harvested from the reserve flasks using trypsin / ethylaminadiamine tetraacetic acid (EDTA). Cell density is measured using a hemocytometer and viability is calculated using blue trypan solution before being seeded at a density of 2x105 cells per cavity of a 6-well plate in DMEM containing 2.5% serum in cardboard strips, 2mM glutamine and amino acids non-essential at 37 ° C in 7.5% CO2 and allowed to settle for 72 hours. After the 72 hour incubation period, serum in medium-containing sera is then replaced with serum-free medium (DMEM containing 2 mM glutamine and non-essential amino acids) and incubated at 37 ° C in 7.5% CO2 for 72 hours. After this incubation period, the cells are treated with or without compound in a concentration range in dimethylsulfoxide (DMSO) (final 0.1%) in serum free DMEM. After incubation for 1.5 hours at 37 ° C in 7.5% CO2, cells were drained with EGF (final concentration of 1 μg / ml) and incubated at 37 ° C in 7.5% CO2 for 3 min. The medium is then removed and the cells are rinsed twice in cold phosphate Regulated Saline before lysis of the cells with 1 ml of cold lysis buffer containing 120 mM NaCl2, 25 mM HEPES, pH 7.5, 5 mM B-Glycerophosphate, 2.5 mM HEPES, pH 7.6 5 mM B-Glycerophosphate, 2.5 mM MgCl2, 1 mM EGTA, 0.2 mM EDTA, 1 mM Na3VO4, 1% Triton X-1 00, 1 00 mM NaF, 1 mM DTT, 1 mM PMSF, 1 0 μg / ml Leupeptin and 10 μg / ml Benzamidine. The lysates are centrifuged in a microfuge at 13000 rpm for 15 minutes and the supernatants taken before analysis by Elisa sandwich. The F96 Maxisorb Nunc immunoplates were screened with EGFR capture antibody (sc-120, Santa Cruz Biotechnology, Inc.) by incubation at a concentration of 0.16 μg / ml in 100 μl of 50 mM carbonate / bicarbonate buffer, pH 9.6. The plates are incubated at 4 ° C overnight with a gentle shaking action. After incubation overnight, the plates are extensively rinsed with PBS containing 0.05% Tween before blocking with Superblock (Pierce). 1 00 μl of lysate is then added to each well and incubated overnight at 4 ° C with an exfoliating rinse with PBS containing 0.05% Tween. Immobilized EGFR is then probed with a HRP anti-phosphoyrosine conjugated antibody (4G 10, Upstate Bio-technology Inc.) at a dilution of 1 in 800 in PBS containing 0.05% Tween plus 0.5% Albumen Bovine Serum. After further rinsing, the HRP activity in each well of the plate is measured colorimically using Tetra Methyl Benzidine (TMB) from Bushranger (Roche Applied Sciences) in phosphate-citrate-perborate buffer containing 1.0% DMSO as a substrafo. This reaction is stopped by the addition of 1 00ul of 1 M H2SO4 after 12 minutes and is quantified by absorbance measurement at 450 nm using a ThermoMax microplate lecimer from Molecular Devices.

The inhibition of EGFR phosphorylation for a given compound is expressed as an IC50 value. This is determined by calculating the compound concentration that is required to give 50% inhibition of phosphorylation in this assay. The phosphorylation range is calculated from the positive (vehicle plus EGF) and negative (vehicle minus EGF) control values. d) 24-phospho-erbB2 clone cell assay The end-point assay of this immunofluorescence measures the ability of a test compound to inhibit the phosphorylation of erbB2 in an MCF7 derived cell line (breast carcinoma) that is generated by transfecting the MCF7 cells with the full-length erbB2 gene using standard methods to give a cell line overexpressing the erbB2 protein of long-range silvesire fiber (hereinafter "Clone 24" cells). Clone 24 cells are grown in Culture Medium (Dulbecco's modified Eagle's medium free of red phenol (DMEM) containing 1 0% of fetal bovine serum, 2 mM glutamine and 1.2 mg / ml G41 8) in 7.5% CO2 of air incubator at 37 ° C. Cells are harvested from T75 stock flasks by rinsing once in PBS (phosphate buffered saline, pH 7.4, Gibco No. 1 001 0-0.15) and harvested using 2 ml of Trypsin solution (1.25 mg (ml)). / ethylaminadiaminotetraacetic acid (EDTA) (0.8mg / ml) Cells are resuspended in Growth Medium Cell density is measured using a haemocytoimage and viability is calculated using Tripan Blue solution before being further diluted in Growth Medium and sowed at a cell density of 1 x1 04 per well (in 100ul) in 96-well clear-bottom wells (Packard, No. 60051 82) 3 days later, the growth medium is removed from the wells and replaced with 1 00 ul Analysis Medium (DMEM free of red phenol, 2mM glutamine, 1.2mg / ml G41 8) either with or without erB inhibitor compound.The plates are returned to the incubator for 4 hours and then 20μl of formaldehyde solution in PBS is added to each cavity and the plate is left to temperaíura ambienie for 30 minutes. This fixed solution is removed with a multichannel pipette, 100 μl of PBS is added to each well and then removed with a multi-channel pipette and then 50 μl PBS is added to each well. The plates are then sealed and stored for up to 2 weeks at 4 ° C. Immunostaining is performed at room temperature.

The wells are rinsed once with 200 μl PBS / Tween 20 (made by adding 1 sachet of dry powder PBS / Tween (Sígma No. P3563) to 1 L of double distilled H2O) using a plate washer after 200 μl of Blocking (5% Marvel dried deslactose milk (Nestle) in PBS / Tween 20) is added and incubated for 10 minutes. The blocking solution is removed using a plate washer and 200 μl of 0.5% Triton X-100 / PBS is added to permeabilize the cells. After 10 minutes, the plate is rinsed with 200 μl PBS / Tween 20 and then 200 μl of Blocking Solution is then added again and incubated for 15 minutes. Following the release of the Blocking Solution with a plate washer, 30 μl of rabbit polyclonal anti-phospho-IgG ErbB2 antibody (epitope phospho-Tyr 1248, Santa Cruz, No. SC-12352-R), diluted 1: 250 in Blocking solution is added, to each cavity and incubated for 2 hours. Then this primary antibody solution is removed from the cavities using a plate washer followed by two washes of 200 μl PBS / Tween using a plate washer. After 30 μl of secondary goat ani-rabbit IgG antibody Alexa-Fluor 488 (Molecular Probes, No. A-1 1008), diluted 1: 750 in Blocking Solution, is added to each well. From now on, when possible, the plates are projected from exposure to light, at this stage when sealing with black backing tape. The plates are incubated for 45 minutes and then the secondary antibody solution is removed from the cavities followed by two washes 200ul PBS / Tween 20 using a plate washer. Then 100 μl of PBS is added to each plate, incubated for 10 minutes and then removed using a plate washer. Then an additional 1 00 μl PBS is added to each plate and then, without prolonged incubation, it is removed using a plate washer. Then 50 μl of PBS is added to each cavity and the plates are resealed with black backing cinya and stored for 2 days at 4 ° C before analysis. The Fluorescence signal in each cavity is measured using an Acumen Bioscience Lid., A plate reader that can be used to quickly quantify the characteristics of images generated by laser scanning. The instrument is set to measure the number of fluorescent objects above a pre-set threshold value and a measurement of the phosphorylation status is provided of the erbB2 protein. The fluorescence dose response obtained with each compound is exported in a suitable software package (such as Origin) to perform the curve fit analysis. The inhibition of erbB2 phosphorylation is expressed as an IC50 value. This is determined by calculating the concentration of compound that is required to give 50% inhibition of erbB2 phosphorylation signal. e) BT-474 Xenograft Assay in vivo This assay measures the ability of a test compound to inhibit the growth of a tumor cell xenograft BT-474 (human mammary carcinoma obtained from Dr Baselga, Oncology Research Laboratory, Paseo Valí D'Hebron 1 1 9-129, Barcelona 08035, Spain) in Swiss amicic mice (Alderley Park, genoípo nu / nu) (Baselga, J. et al. (1 998) Cancer Research, 58 , 2825-2831). Female Swiss nude mice (genotype nu / nu) are fed and maintained at Park Alderley in Negative Pressure Isolators (Sisiemas PFI Ltd.). The mice are housed in a barrier equipment with 12hr light / dark cycles and is provided with food and water ad libitum. All procedures are performed on mice at least 8 weeks old. Tumor cell xenografts BT-474 are established on the hidden flank of donor mice by subcutaneous injection of 1 x 10 7 cells newly cultured in 100 μl of serum free medium with 50% Matrigel per animal. On the 14th day after implantation, the roots are alloyed in groups of 10% of the treatment with compound or vehicle control that is administered only once a day at 0.1 ml / 10 g of body weight. Tumor volume is titrated twice per week by bilateral Vernier caliper measurement, using the formula (length x width) xV (longifudx width) x (p / 6), where the length was the longest diameter across the tumor, and the width was the corresponding perpendicular. The inhibition of growth from the beginning of the frafamienfo is calculated in comparison of the average changes in tumor volume for the control and treated groups, and the statistical significance between the two groups is evaluated using a Studenís t test. f) Potassium Channel Inhibition Assay encoded by hERG This assay determines the ability of a test compound to inhibit the subsequent current flowing through the potassium channel encoded by the ether related gene (Herg). Human embryonic kidney (HEK) cells expressing the hERG-encoded channel where they develop in Eagle's Minimum Essential Medium (EMEM); catalog number Sigma-Aldrich M2279), supplemented with 1 0% Fetal Bovine Serum (Labtech International, product number 4-101 -500), 10% serum-free complement (Egg Technologies, product number 70916) and 0.04 mg / ml Generation G418 (Sigma-Aldrich, catalog number G7034). One or two days before each experiment, the cells are separated from the culture flasks with Accuíase (TCS Biologícals) using standard yeast culture methods. They are then placed on glass slides resting in cavities of a 12-well plate and covered with 2 ml of the growth medium. For each registered cell, a glass slide containing the cells is placed in the bottom of a Perspex chamber containing bath solution (see below) at room temperature (~ 20 ° C). This camera is fixed at the stage of a phase contrasie microscope, inverted. Immediately after placing the slide in the chamber, the bath solution is filtered in the chamber from a container fed by gravity for 2 min. At a rate of ~2 ml / min. After this time, the perfusion stops. A patch pipette made of borosilicate glass tubing (GC120F, Harvard Apparatus) using a P-97 micropipette handler (Sutimer I nsfrument Co.) is filled with pipette solution (see hereafter). The pipette is connected in the upper layer of the patch clamp amplifier (Axopatch 200B, Axon Insfrumenís) through a silver / platinum chloride wire. The terrain in the upper stage is connected to the earth electrode. This consists of a silver / silver chloride wire embedded in 3% agar made with 0.85% sodium chloride. The cell is recorded in the complete cell configuration of the patch clamp technique. Following the "introduction", which is done at a conservation potential of -80 mV (fixed by the amplifier), and appropriate adjustment of series resistance and capacitance levels, electrophysiology software (Clampex, Axon Instrumenís) is used to fix a conservation potential (-80 mV) and to supply a voltage procedure. This procedure is applied every 1 5 seconds and consists of a 1 s to +40 mV step followed by a 1 s to -50 mV step. The current response to each imposed voltage procedure is filtered in low pass through the amplifier at 1 kHz. The filtered signal is then acquired, online, by digitizing this analog signal from the amplifier with an analog-to-digital converter. The digitized signal is then captured on a computer running Clampex software (Axon I nstruments). During the conservation potential and the stage at +40 mV the current is sampled at 1 kHz. The sampling rate is then set to 5 kHz for the rest of the voltage procedure. The compositions, pH and osmolarity of the bath and pipette solution are tabulated below.

The amplitude of the downstream stream of poiasis channel encoded by hERH following the step from +40 mV to -50 mV is recorded online by Clampex software (Axon Instruments). Following the stabilization of the rear current amplitude, the bath solution containing the vehicle for the test subsidence is applied to the cell. Providing the vehicle application had no significant effect on subsequent current amplitude, a cumulative concentration effect curve to the composite is then considered. The effect of each concentration of test compound is quantified by expressing the subsequent current amplitude in the presence of a given concentration of a test compound as a percentage of that in the presence of vehicle. The power of compound test (IC50) is determined by adjusting the percentage inhibition values by elaborating the concentration effect to a Hill equation of four parameters using a standard data adjustment package. If the level of inhibition observed at the test concentration plus alpha does not exceed 50%, no power value is produced and a percentage inhibition value at that concentration is quoted. Although the pharmacological properties of the compounds of the formula I vary with structural change as expected, in general activity possessed by the compounds of the formula I, they can be demonstrated in the following concentrations or doses in one or more of the above tests (a) , (b), (c) and (d) -: Test (a): - IC50 in the range, for example, 0.001 -5 μM; Test (b): - IC50 in the range, for example, 0.001 -5 μM; Test (c): - IC50 in the range, for example, 0.001 -5 μM; Test (c): - IC50 in the range, for example, 0.001 -5 μM; Test (d) activity in the range, for example, 1 -200 mg / kg / day; No physiologically acceptable toxicity is observed in Test (d) at the effective dose for the tested compounds of the present invention. Accordingly, non-toxicological effects are not expected when a compound of formula I, or a pharmaceutically acceptable salt thereof, as defined herein above is administered in the dosage ranges defined below. By way of example, Table A illustrates the activity of representative compounds according to the invention. Column 2 of Table A shows IC50 data from Test (a) for the inhibition of phosphorylation of EFGR tyrosine kinase profine, column 3 shows IC 50 data from Test (a) for the inhibition of tyrosine kinase phosphorylation erbB2; and column 4 shows IC 50 for inhibition of erbB2 phosphorylation in a cell derivative MCF7 in Test (d) described above.

Table A According to a further aspect of the invention there is provided a pharmaceutical composition comprising a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, as defined hereinbefore in association with a pharmaceutically acceptable diluent or carrier. The compositions of the invention may be in a form suitable for oral use (for example, as tablets, dragees, hard or soft capsules, aqueous or oily suspensions, emulsions, granules or dispersible powders, syrups or elixirs), for topical use (for example as creams, ointments, gels or suspensions or aqueous or oily solutions), for administration by inhalation (for example as a finely divided powder or a liquid aerosol), for administration by insufflation (for example, as a finely divided powder) or for parenteral administration (eg, as a sterile aqueous or oily solution for intravenous, subcutaneous, intramuscular dosing or as a suppository for rectal dosing). The compositions of the invention can be obtained by conventional procedures using conventional pharmaceutical excipients, well known in the art. In this way, compositions proposed for oral use may contain, for example, one or more colorant, sweetening, flavoring and / or preservative agents. The amount of the active ingredient that is combined with one or more excipients to produce a single dosage form will necessarily vary depending on the host treated and the particular route of administration. For example, a proposed formulation for oral administration to humans will generally contain, for example, 0.5 mg to 0.5 g of the active agent (more preferably 0.5 to 100 mg, for example 1 to 30 mg) composed of an appropriate amount and convenience of excipients which may vary from about 5 to about 98 weight percent of the oral composition. The size of the dose for prophylactic or therapeutic purposes of a quinazoline derivative of formula I will naturally vary according to the nature and severity of the conditions, the age and sex of the animal or patient and the route of administration, according to principles of well-known medicine. When using a quinazoline derivative of formula I for prophylactic or therapeutic purposes it will generally be administered so that a daily dose in the range, for example, 0.1 mg / kg to 75 mg / kg of body weight is received, given if required in divided doses. In general, lower doses will be administered when a parenteral route is used. Thus, for example, for intravenous administration, a dose in the range, for example, 0.1 mg / kg to 30 mg / kg body weight will generally be used. Similarly, for administration by inhalation, a dose in the range, for example, 0.05 mg / kg to 25 mg / kg of body weight will be used. Oral administration, however, is preferred, particularly in the form of diabetes. Typically, the unit dosage forms will contain about 0.5 mg to 0.5 g of a compound of this invention. We have found that the compounds of the present invention possess anti-proliferative propes such as anti-cancer propes that are believed to originate from their erb-B, particularly EGFR and more particularly inhibitory activity of receptor tyrosine kinase erbB2. In addition, cin of the compounds according to the present invention possess substantially better potency against the tyrosine receptacle kinase erbB2, than against other tyrosine kinase enzymes, such as EGFR tyrosine kinase. Such compounds possess sufficient potency against the erbB2 receptor tyrosine kinase which can then be used in a sufficient amount to inhibit tyrosine kinase of the erbB2 receptor while showing little, or significantly low activity against other tyrosine kinases such as EGFR. Such compounds are probably useful for the selective inhibition of erbB2 receptor tyrosine kinase and are probably useful for effective treatment of, for example, erbB2-driven tumors. Accordingly, the compounds of the present invention are expected to be useful in the treatment of diseases or medical conditions mediated alone or in part by an erb-B receptor tyrosine kinases, particularly erbB2, ie the compounds can be used to produce an erb-B receptor tyrosine kinase inhibitory effect, particularly an erbB2 in a warm-blooded animal in need of such treatment. In this manner, the compounds of the present invention provide a method for the eradication of malignant cells characterized by inhibition of the tyrosine kinase of the erb-B receptor, particularly erbB2. Particularly the compounds of the invention can be used to produce an antimicrobial and / or pro-apoptotic and / or anti-proliferative effect mediated alone or in part by the inhibition of receptor tyrosine kinases erb-B, particularly erbB2. Particularly, the compounds of the present invention are expected to be useful in the prevention or treatment of those tumors that are sensitive to inhibition of an erb-B receptor tyrosine kinase., particularly erbB2, which are included in the signal transduction stages that trigger the proliferation and survival of these tumor cells. In accordance with the foregoing, the compounds of the present invention are expected to be useful in the irradiation and / or prevention of a number of hyperproliferative disorders by providing an anti-proliferative effect. These disorders include, for example, psoriasis, benign prostatic hyperplasia (BPH), atherosclerosis and resenosis, and receptor-activated tyrosine kinase, in particular erb-B, more particularly erb-B2.

Such benign or malignant tu can affect any tissue and include non-solid tu such as leukemia, multiple myeloma or lymphoma, and also solid tu, eg, bile duct, bone, bladder, brain / CNS, breast, colorectal, cervical, endometrial, gastric, head and neck, hepatic, lung, muscle, neuronal, osophageal, ovarian, pancreatic, pleural / peri-neal, prosaic, renal, skin, testicular, thyroid, uterine, and vulvar tu. According to this aspect of the invention there is provided a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, to be used as a medicament. Thus according to this aspect of the invention there is provided the use of a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, as defined herein above in the manufacture of a medicament for use in the production of an antiproliferative effect in a warm-blooded animal such as human. According to a further feature of this aspect of the invention there is provided a method for producing an anti-proliferafive effect in a warm-blooded animal, such as human, in need of irradiation which comprises administering to said mammal an effective amount of a a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, as defined herein above. According to a further aspect of the invention there is provided a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, to be used in the production of an anti-proliferative effect in a warm-blooded animal such as human. According to a further aspect of the invention there is provided the use of a quinazoline derivative of formula 1, or a pharmaceutically acceptable salt thereof, as defined herein above in the manufacture of a medicament for use in the production of an anti-proliferative effect, such an effect occurs only or in part by inhibiting the receptor tyrosine kinase erbB2 in a warm-blooded animal such as human. According to a further feature of this aspect of the invention, a method is provided for producing an amino-proliferative effect, the effect being produced only or in part by inhibiting tyrosine kinase of the erbB2 receptor in a warm-blooded animal, such as human, in need of such a process comprising administering to said animal an effective amount of a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt, as defined hereinbefore. According to a further aspect of the invention there is provided a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, for use in the production of an anti-proliferative effect, such effect occurs only or in part to the inhibiting receptor tyrosine erbB2 kinase in a warm-blooded animal such as human.

According to a further aspect of the present invention there is provided in this way the use of a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, as defined above in the present in the manufacture of a medicament for use in the treatment of a disease or medical condition (eg, a cancer as mentioned herein) mediated alone or in part by tyrosine kinase of the erb-B receptor, particularly erbB2. According to a further feature of this aspect of the invention there is provided a method for bringing a disease or medical condition (eg, a cancer as mentioned herein) mediated alone or in part by tyrosine kinase of the erb-B receptor, particularly erbB2, in a warm-blooded animal, such as human, in need of treatment, which comprises administering to said animal an effective amount of a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, as defined hereinbefore. According to a further aspect of the invention there is provided a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt, for use in the eradication of a disease or medical condition (for example, a cancer as mentioned in the present) mediated alone or in part by erin-B receptor tyrosine kinase, particularly erbB2. According to a further aspect of the invention there is provided in this way the use of a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, as defined herein above in the manufacture of a medicament for use in the prevention or treatment of those tumors that are sensitive to tyrosine kinase inhibition of the erbB2 receptor that is included in the signal transduction steps that leads to the proliferation of tumor cells. According to a further feature of this aspect of the invention, a method is provided for the prevention or treatment of those tumors that are sensitive to the inhibition of tyrosine kinase of the erbB2 receptor, which is included in the signal transduction cells that lead to the proliferation and / or survival of tumor cells in a warm-blooded animal, such as human, in need of such an irradiation, which comprises administering to said animal an effective amount of a quinazoline derivative of the formula I, or a pharmaceutically salt thereof. acceptability thereof, as defined in the foregoing. According to a further aspect of the invention there is provided a chenazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, for use in the prevention or treatment of those tumors which are sensitive to inhibition of the receptor tyrosine kinase erbB2 , which is included in the signal transduction pathways that lead to the proliferation and / or survival of tumor cells. According to a further aspect of the invention there is provided the use of a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, as defined herein above in the manufacture of a medicament for use in providing an effec tyrosine kinase inhibitor of the erbB2 receptor. According to a further feature of this aspect of the invention, a method is provided for providing a receptor tyrosine kinase inhibitor erbB2 effect in a warm-blooded animal, such as human, in need of such treatment, comprising administering to said animal a effective amount of a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt, as defined herein above. According to a further aspect of the invention there is provided a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, to be used to provide an inhibitory effect of erbB2 receptor kinase. According to a further aspect of the invention there is provided the use of a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, as defined hereinabove in the manufacture of a medicament for use in providing an effect erbB2 kinase inhibitor. According to a further feature of this aspect of the invention there is provided a method for providing a selective erbB2 kinase inhibitory effect in a warm-blooded animal, such as human, in need of such a fratamment, which comprises administering to said animal an amount of a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt, as defined herein. According to a further aspect of the invention there is provided a quinazoline derivative of the formula I, or an acceptable pharmaceutically acceptable salt thereof, for use in providing a selective erbB2 kinase inhibitory effect. By "selective erbB2 kinase inhibitory effect" is meant that the quinazoline derivative of Formula I is more potent against tyrosine kinase of the erbB2 receptor which is against other kinases. In particular, some of the compounds according to the invention are more potential confra receptors kinase erbB2 which is conira oras firosin kinases such as other receptor tyrosine kinases erb-B, particularly EGFR tyrosine kinase. For example, a selective erb-B2 kinase inhibitor according to the invention is at least 5-fold, preferably at least 10-fold, more preferably at least 100-fold more likely than the receptor kinase erbB2 which is against EGFR tyrosine kinase, as is determined from the relative IC 50 values in suitable assays (eg, by comparing the IC50 value of the phospho-erbB2 cell Clone 24 assay (assay d) described above which measures the inhibition of erb-B2 phosphorylation in cells) with IC5_ of the assay of cellular EGFR phosphorylation KB (assay c) described above which measures the inhibition of EGFR phosphorylation in cells) for a given test compound as described above). According to a further aspect of the present invention there is provided the use of a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, as defined herein above in the manufacture of a medicament for use in treatment of a cancer, for example, a cancer selected from leukemia, multiple myeloma, lymphoma, bile duct, bone, bladder, brain / CNS, breast, colorectal, cervical, endometrial, gastric, head and neck, hepatic, lung, muscle, neuronal , osophageal, ovarian, pancreatic, pleural / peritoneal membranes, prostate, renal, skin, soleus, thyroid, uterus and vulval cancer. According to a further feature of this aspect of the invention a method for irradiating a cancer is provided, for example a cancer selected from leukemia, multiple myeloma, lymphoma, bile duct, bone, bladder, brain / CNS, breast, colorectal, cervical , endometrial, gastric, head and neck, hepatic, lung, muscle, neuronal, osophageal, ovarian, pancreatic, pleural / peri-neal, prostate, renal, skin, testicular, thyroid, uterine, and vulval cancer in a warm-blooded animal, such as a human, in need of such a trait, comprising administering to said animal an effective amount of a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, as defined herein. According to a further aspect of the invention there is provided a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, for use in the treatment of a cancer, for example a cancer selected from leukemia, multiple myeloma, lymphoma, biliary duct, bone, bladder, brain / CNS, breast, colorectal, cervical, endometrial, gastric, head and neck, hepatic, lung, muscle, neuronal, osofageal, ovarian, pancreatic, pleural / peritoneal membranes, prostate, renal, skin, Indicate, thyroid, uterine and vulval cancer. The anti-proliferative treatment defined herein may be applied as a single therapy and may include, in addition to the quinazoline derivative of. the invention, conventional surgery or radiotherapy or chemotherapy. Such chemotherapy may include one or more of the following categories of antimicrobial agents: as mentioned above, the dose size required for the therapeutic or prophylactic irradiation of a particular disease will necessarily vary depending on, among other things, the trampled host, the route of administration and the severity of the disease being treated. The anti-proliferative trafficking defined herein may be applied as a single therapy or may include, in addition to the quinazoline derivative of the invention, conventional surgery or radiotherapy or immunotherapy. Such chemo-therapy may include one or more of the following categories of amphe-tumor agents: (i) antiproliferative / antineoplastic drugs and combinations thereof, as used in medical oncology, such as alkylating agents (eg cis-platin, carboplatin) , cyclophosphamide, nifrogen mustard, melphalan, chlorambucil, busulfan and nitrosureas); antimetabolites (for example, antifolates such as fluoropyrimidines such as 5-fluorouracil and tegafur, raltitrexate, methotrexate, cytosine arabinoside and hydroxyurea; antitumor antibiotics (eg, anthracyclines such as adriamycin, bleomycin, doxorubicin, daunomycin, epirubicin, idarubicin, miomycin-C, dactinomycin and mitramycin), antimitotic agents (for example, vinca alkaloids such as vincrastine, vinblastine, vindesine and vinorelbiba and taxoids such as taxol and taxotere), and topoisomerase inhibitors (for example, epipopophyllotoxins such as etoposide and teniposide, amsacrine, topotecan and canpothecin); (ii) cytostatic agents such as antiestrogens (e.g., tamoxifen, toremifene, raloxifene, droloxifene, and iodoxifene), estrogen receptor sub-regulators (e.g., fulvestrant), antiandrogens (e.g., bicalutamide, flutamide, nilutamide, and cyproterone acetate) , LHRH anolygonias or LHRH agonisías (for example goserelin, leuprorelin and busereli na), progestogens (e.g., megestrol acetate), aromaroma inhibitors (e.g., anastrazole, letrozole, vorazole and exemesin) and 5a-reductase inhibitors such as finasteride; (ii) agents that inhibit cell invasion by cancer (eg, metallopropylinase inhibitors such as marimastat and inhibitors of urokinase plasminogen activator receptor function); (iv) inhibitors of growth factor function, for example such inhibitors include growth factor antibodies, growth factor receptor antibodies (for example, the anti-erbB2 transuzuzumab [Herceptin ™] antibody and the anti-erbB1 cetuximab antibody [C225]), farnesyl transferase inhibitors, tyrosine kinase inhibitors, and threonine serine / kinase inhibitors, for example, other inhibitors of the epidermal growth factor family (eg, EGFR family tyrosine kinase inhibitors such as JN- (3-chloro-4-fluorophenyl) -7-methoxy-6- (3-morpholinopropoxy) quinazolin-4-amine (gefitinib, AZD1 839), JN- (3-ethynylphenyl) -6,7-bis (2 -methoxy-exoxy) quinazolin-4-amine (erlotinib, OSI-774) and 6-acplamido-JN- (3-chloro-4-p-fluorophenyl) -7- (3-morpholinopropoxy) quinazolin-4-amine (Cl 1 033)) , for example inhibitors of the platelet derived growth factor family and for example inhibitors of the growth factor family of and hepatocyst; (v) antiangiogenic agents such as those that inhibit the effects of vascular endothelial growth factor, (e.g., the anothelial vascular endothelial cell growth factor antibody bevacizumab [Avastin ™], compounds such as those described in the patent applications. International patent WO 97/22596, WO 97/30035, WO 97/32856 and WO 98/1 3354) and compounds which function by other mechanisms (for example, linomide, inhibitors of avß3 function and angiosphaine); (vi) vascular damage agents such as Combretastatin A4 and compounds described in International Patent Applications WO 99/02166, WO 00/40529, WO 00/41669, WO 01/9224, WO 02/04434 and WO 02/0821 3; (vii) aníisentido ferapias, for example those that address the objectives listed above, such as ISIS 2503, an anti-ras antisense; (viii) gene therapy approaches, including for example plans to replace aberrant genes such as aberrant p53 or aberrant BRCA1 or BRCA2, GDEPT (gene-directed enzyme pro-drug therapy) such as those using cytosine deaminase, kinase of thymidine or a bacterial nitroreductase enzyme and approaches to increase patient tolerance to chemotherapy or radiation therapy as genetic therapy for multidrug resistance; and (x) immunotherapy approaches, including for example ex vivo and in vivo approaches to increase the immunogenicity of patient tumor cells, as well as transfection with cytokines such as interluequin 2, inerieucin 4 or macrophage colony stimulating factor. granulocyte, approaches to reduce the energy of the T cell, approaches using transfected immune cells such as dendritic cells transfected by cytokine, approaches using tumor cell strains transfected by cytokine and approaches using anti-idiotypic antibodies. Such joint treatment can be achieved in the manner of simultaneous, sequential or separate dosing of the individual components of the treatment. Such combination products employ the compounds of this invention within the dosage range described hereinbefore and the other pharmaceutically active agent within its approved dosage range. According to this aspect of the invention there is provided a pharmaceutical product comprising a quinazoline derivative of the formula I as defined hereinbefore and an additional anti-tumor agent as defined hereinbefore for the combined traisation of cancer. Although the compounds of formula I are primarily of value as therapeutic agents for use in warm-blooded animals (including human), they are also useful whenever required to inhibit the effects of receptor tyrosine protein kinases erbB. In this way, they are useful as pharmacological standards to be used in the development of new biological tests and in the search for new pharmacological agents. The invention will now be illustrated by the following non-limiting examples in which, unless stated otherwise: (i) temperatures are given in degrees Celsius (° C); operations are carried out at ambient temperalure, that is, at an operation in the range of 8-25 ° C; (ii) organic solutions are dried over anhydrous magnesium sulfate; Solvent evaporation is carried out using a rotary evaporator under reduced pressure (600-4000 Paséales; 4.5-30mmHg) with a bath temperature of up to 80 ° C; (iii) chromatography means flash chromatography on silica gel; Thin layer chromatography (TLC) is carried out on silica gel plates; (iv) in general, the course of reactions is followed by TLC and / or analytical LC-MS, and reaction times are given for illustration only; (v) final products had satisfactory proton nuclear magnetic resonance (NMR) spectra and / or mass spectral data; (vi) products are given for illustration only and are not necessarily those that can be obtained by diligent process development; preparations are repeated if more material is required; (vii) when given, NMR data are in the form of delta values for major diagnostic protons, given in parts per million (ppm) relative to tetramethylsilane (TMS) as an internal standard, determined at 300 MHz using dimethyl sulfoxide perdeuterio (DMSO-d6) as solvents unless otherwise indicated; the following abbreviations have been used: s, singlet; d, doublet; t, complete it; q, cuarfeío; m, multiplet; b, broad; (viii) chemical symbols have their usual meanings; SI units and symbols are used; (ix) solvent proportions are given in terms of volume: volume (v / v); and (x) mass spectra are run with an electron energy of 70 volts of elecron in the chemical ionization mode (Cl) using a direct exposure probe; wherein the indicated ionization is effected by electron impact (El), fast atom bombardment (FAB) or electroacoustic (ESP); values for m / z are given; Generally, only ions that indicate the mass of origin are reported; and unless stated otherwise, the graded mass ion is (MH) + which refers to the mass ion profonated; reference to M + is the mass ion generated by loss of an electrophile; and reference to M- H + is the mass ion generated by the loss of a proton; (xi) unless otherwise stated the compounds containing an asymmetrically substituted carbon and / or sulfur atom have not been resolved; (xii) where a synthesis is described as being analogous to that described in a previous example, the used quantities are the millimolar ratio equivalents to those used in the previous example; (xiíi) all microwave reactions are carried out in a microwave synthesis CEM Discover ™ or microwave synthesizer CEM Marrs; (xiv) preparative high performance liquid chromatography (HPLC) is performed on a Wilson instrument using the following conditions: Column: 21 mm x 10 cm Hichrom RPB Solvenie A: Water + 0.1% trifluoroacetic acid, Solvent B: Acetonitrile + 0.1% acid trifluoroacetic, Flow rate: 18 ml / min Run time: 15 minutes with a gradient of 1 0 min. of 5-95% B Wavelength: 254 nm, bandwidth 10 nm Injection volume: 2.0-4.0 ml; (xv) the following abbreviations have been used: HATU O- (7-Azabenzoyriazol-1-yl) -N, N, N ', N'-TetrameyyluroniumHexafluoro-Phosphation; and THF εtrahydrofuran; DMF? /,? / - dimethylformamide; DMA? /,? / - dimethylacetamide; DCM dichloromethane; DIPEA N, N-diisopropylethylamine; DMSO dimethylsulfoxide; IPA isopropyl alcohol; and Diethyl ether.

Example 1 W-. { 2 - [(4-. {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} -? / - methylacetamide A mixture of HATU (1 97 mg), diisopropylethylamine (90 μl), acetic acid (22 μl) and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (methylamino) eioxy] qinazolin-4-amine (150 mg) in DCM (20 ml) is stirred for 2 hours. The solution is rinsed with water, then brine and concentrated in vacuo. The residue is purified by chromafography using DCM-5% methanol as eluent to give the title compound as a white solid (14mg, 69%); NMR spectrum (DMSO-d6) 1.95 (s, 3H), 3.00 (s, 3H), 3.89 (t, 2H), 4.48 (m, 2H), 5.29 (s, 2H), 7.18 (d, 1) H), 7.24 (d, 1 H), 7.35 (m, 2H), 7.59 (m, 2H), 7.72 (d, 1 H), 7.85 (dt, 1 H), 7.96 (d, 1 H), 8.46 (s, 1 H), 8.58 (m, 1 H), 9.70 (bs, 1 H); Mass Spectrum MH + 478.5. ? / - [3-Chloro-4- (pyridin-2-ylmeyoxy) phenyl] -5- [2- (meitylamino) eioxy] qinazolin-4-amine used as starting material is prepared as follows: DMF (0.2 ml) is add to a 5-fluoro-3 suspension, 4-dihydro-3H-quinazolin-4-one (1.64 g) in ionyl chloride (10 ml) and the mixture was stirred and heated at 80 ° C for 6 hours. Volatile material is removed by evaporation and the residue azeotroped with toluene (20 ml). The resulting solid is added per portion to a vigorously stirred mixture of saturated sodium bicarbonate (50 ml), crushed ice (50 g) and DCM (50 ml) so that the temperature is maintained below 5 ° C. The organic phase is separated, dried and concentrated to give 4-chloro-5-fluoroquinazoline (1.82 g, 99%) as a solid which is used without purification; NMR spectrum (CDCI ..) 7.35-7.45 (m, 1 H), 7.85-7.95 (m, 2H), 9.0 (s, 1 H). 4-Chloro-5-fluoroquinazoline (6.75 g) is added to a stirred solution of 3-chloro-4- (2-pyridylmethoxy) aniline (9.27 g, obtained as described in Example 15-21 (note u) of WO 96/1 51 1 8) in I PA (200 ml), and the solution is stirred and heated to reflux for 8 hours. The solution is allowed to cool to ambient temperature overnight and the precipitated solid is filtered, rinsed with acetone and dried. The solid is added to 50% aqueous methanol (400 ml) and the mixture is heated in a steam bath until the complete solid has dissolved. The solution is made basic by careful addition of aqueous ammonium (0.880) and the mixture is concentrated to remove meianol. Water (300 ml) is added and the mixture is extracted with DCM (600 ml). The extract is rinsed with water, and brine, and dried. The solvent is removed by evaporation to give a solid, which is re-precipitated from a mixture of ethyl acetate, tetrahydrofuran and isohexane to give? / - [3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] -5 -fluoroquinazolin-4-amine as a beige solid (6.75 g, 48%); Specimen NMR (DMSO-d6) 5.3 (s, 2H), 7.2-7.3 (d, 1 H), 7.35-7.5 (m, 2H), 7.5-7.65 (m, 3H), 7.8-7.95 (m, 3H) , 8.55 (s, 1H), 8.55-8.6 (d, 1H), 9.1-9.2 (bs, 1H); Mass Spectrum MH + 381. Sodium hydride (60% dispersion in mineral oil, 0.63 g) is added to 2- (methylamino) ethanol (0.95 ml), 15-crown-5 and? / - [3-chloro-4- (pyridin-2-ylmethoxy Phenyl] -5-fluoroquinazolin-4-amine (1.5 g) in DMA (25 ml) and the reaction is heated at 100 ° C for 2 hours. The reaction is cooled, quenched with saturated aqueous ammonium chloride solution at pH 7-8. Addition of a small amount of saturated aqueous sodium hydrogen carbonate solution results in the formation of a precipitate, which is filtered, rinsed with water and dried. The solid is purified by chromatography using DCM-5% methanol / 7N ammonium as eluent to give? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (methylamino) ethoxy] quinazolin -4-amine as a yellow solid (0.27 g, 45%); NMR spectrum (DMSO-d6) 2.40 (s, 3H), 3.02 (i, 2H), 4.35 (t, 2H), 5.28 (s, 2H), 7.12 (d, 1H), 7.25 (d, 1H), 7.31 (d, 1H), 7.37 (m, 1H), 7.57 (d, 1H), 7.71 (dd, 1H), 7.85 (m, 2H), 8.10 (d, 1H), 8.51 (s, 1H), 8.58 ( m, 1H), 10.57 (bs, 1H); Mass specifier MH + 436.5. Example 2 Using a procedure analogous to that described in Example 1, the appropriate quinazoline is reacted with the appropriate acid to give the compounds shown in Table I: Table I [1] _V-. { 2 - [(4-. {3-Chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} -2-methoxy- > V-methylacetamide. Prepared by reacting methoxyacetic acid and? / - [3-chloro-4- (pyridin-2-ylmethoxy) ethoxy] phenyl] -5- [2- (methylamino) ethoxy] quinazolin-4-amine (prepared as described in Example 1, preparation of initial materials) in 52% production; NMR spectrum (DMSO-d6) 3.00 (s, 3H), 3.23 (s, 3H), 3.90 (t, 2H), 4.04 (s, 2H), 4.50 (t, 2H), 5.29 (s, 2H), 7.17 (d, 1H), 7.23 (d, 1H), 7.35 (m, 2H), 7.59 (dd, 1H), 7.72 (dd, 1H), 7.85 (dt, 1H), 7.99 (d, 1H), 8.45 ( s, 1H), 8.58 (m, 1H), 9.70 (bs, 1H); Mass Spectrum MH + 508.5. [2] ?/-. { 2 - [(4- {3-Chloro-4- (pyridin-2-ylmethoxy) anilino} quinazoIin-5-yl) oxy] ethyl} -2- (dimethylamine) -W-methylacetamide. Prepared by reacting? /,? / - dimethylglycine and? / - [3-chloro-4- (pyridin-2-I methoxy) ethoxy] phenyl] -5- [2- (m ethyl am i no) ethoxy] quinazolin -4-amine (prepared as described in Example 1, preparation of starting materials) in 13% yield; NMR spectrum (DMSO-d6) 2.68 (s, 6H), 3.05 (s, 3H), 3.97 (m, 2H), 4.05 (s, 2H), 4.53 (m, 2H), 5.29 (s, 2H), 7.19 (d, 1H), 7.26 (d, 1H), 7.37 (m, 2H), 7.60 (d, 1H), 7.65 (d, 1H), 7.54 (i, 1H), 7.86 (dt, 1H), 8.02 ( d, 1H), 8.50 (s, 1H), 8.58 (m, 1H), 9.70 (bs, 1H); Mass Spectrum MH + 521.6. [3]? F-. { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propiI} -2-methoxy -? / - methylacetamide Prepared by reacting methoxyacetic acid (methylamino) and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5 - [(1) -1-methyl-2 - (methylamino) ethoxy] quinazolin-4-amine in 31% yield; Mass Spectrum MH + 522.4. ? / - [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] -5 - [(1 R) -1-methyl-2- (methylamino) ethoxy] quinazolin-4-amine used as starting material is prepared as follows: (2R) -2-Methyldiran (1.76 g) is added to a suspension of? / -mephylprop-2-en-1-amine (25 ml) and ytterbium trifluoromethanesulfonate (III) (100 mg) in dioxane (100 ml) and heated at 140 ° C for 1 hour under microwave irradiation. The solution is concentrated in vacuo and the residue is partitioned between water (100 and ethyl acetate (200 ml) .The organic extractant is dried and the solveny is removed in vacuo yielding (2R) -1 - [allyl (meth) amino) ] propan-2-ol as a yellow oil (8.8 g, 29%); NMR spectrum (CDC) 1 .20 (d, 3H), 2.33 (s, 3H), 2.27-2.46 (m, 2H), 3.05 ( m, 1 H), 3.23 (m, 1 H), 3.88 (m, 1 H), 5.1 9-5.29 (m, 2H), 5.90 (m, 1 H); Mass Spectrum MH * 129. (2R) -1- [allyl (meiyl) amino] propan-2-ol is reacted with N- [3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] -5-fluoroquinazolin-4-amine using an analogous procedure to that described in Example 1 for the preparation of? / - [3-chloro-4- (pyridin-2-ylmefoxyl) phenyl] -5- [2- (methylamino) ethoxy] quinazoln-4-amine , to give 5- { (1 R) -2- [allyl (methyl) amino] -1-methylethoxy.} -? / - [3-chloro-4- (pyridin-2-ylmefoxy) phenyl] quinazolin -4-amine in 53% production, NMR spectrum (DMSO-d6) 1.45 (d, 3H), 2.17 (s, 3H), 2.92-3.07 (m, 2H), 4.93 (m, 1 H), 5.00 (d, 1 H), 5.1 0 (d, 1 H), 5.30 (s, 2H), 5.64 (m, 1 H), 7.20-7.40 (m, 4H), 7.58 (m, 2H), 7.71 (dd, 1 H), 7.85 (dd, 1 H), 7.98 (m, 1 H), 8.47 (s, 1 H), 8.58 (d, 1 H), 1 0.32 (ds, 1 H). 5-. { (1 R) -2- [allyl (methyl) amino] -1-methylethoxy} -? / - [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] -nazazolin-4-amine is heated in acetonitrile / water in the presence of chlorohydris (triphenylphosphine) rhodium (I) using a procedure analogous to that described below in Example 4-1 1 (preparation of starting materials) to give? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5 - [(1 R) -1-methyl-2 - 10. (methylamino) ethoxy] quinazolin-4-amine in 15% yield; Specie of Mass MH + 450. [4] W-. { (1 R) -2 - [(4- {3-Chloro-4- (pyridin-2-ylmethoxy) anilino} qui-nazolin-5-yl) oxy] -1-methyl-ethyl} acetamide. Prepared when reacting 5-. { [(2R) -2-aminopropyl] oxy} -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine and acetic acid in 99% yield; NMR spectrum (DMSO-d6) 1 .20 (d, 3H), 1 .70 (s, 3H), 4.2- 4.3 (m, 2H), 4.4 (m, 1 H), 5.35 (s, 2H), 7.3 -7.6 (m, 6H), 7.8 (m, 1 H), 7.85-8.00 (m, 2H), 8.15 (d, 1 H), 8.6 (d, 1 H), 8.8 (s, 1 H); Mass Spectrum MH + 478. 20 5-. { [(2R) -2-aminopropyl] oxy} -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine used as starting material is prepared by reacting (R) - (-) - 2-amino-1-propanol and? / - [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] -5-fluoroquinazolin-4-amine using a procedure analogous to that described in Example 1 (for the preparation of to give? / - [3 -chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (meitylamino) ethoxy] quinazolin-4-amine to give 5- { [(2R) -2-aminopropyl] oxy}. -? / - [3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] quinazolin-4-amine in 63% yield: NMR specimen (DMSO-d6) 1.20 (d, 3H), 3.4 (m, 1H) , 4.0 (f, 1H), 4.2 (dd, 1H), 5.3 (s, 2H), 7.1 (d, 1H), 7.2 (d, 1H), 7.3 (m, 2H), 7.6 (d, 1H), 7.7 (m, 2H), 7.9 (m, 1H), 8.25 (d, 1H), 8.5 (d, 1H), 8.6 (d, 1H), Mass Spectrum MH + 436. [5]? R- { (1R) -2 - [(4- {3-Chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] -1-methylethyl} -2-hydroxyacetamide. Prepared by reacting glycolic acid and 5- { [(2R) -2-aminopropyl] oxy.} -? / - [3-chloro-4- (pyridine- 2-ylmethoxy) pheny1] quinazolin-4-amine in 93% yield; NMR spectrum (DMSO-d6) 1.20 (d, 3H), 3.6-3.8 (m, 2H), 4.3 (m, 2H), 4.5 (m, 1H), 5.35 (s, 2H), 7.25-7.60 (m, 6H), 7.80-7.95 (m, 3H), 8.00 (d, 1H), 8.60 (d, 1H), 8.6 (d, 1H), 8.75 (s, 1H); Mass Spectrum MH + 494. [6] W-. { 2 - [(4-. {3-Chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} acetamide. Prepared by reacting acetic acid with 5- (2-aminoethoxy) - / V- [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine in 63% yield; NMR spectrum (DMSO-d6) 1.78 (s, 3H), 3.62 (m, 2H), 4.34 (t, 2H), 5.29 (s, 2H), 7.14 (d, 1H), 7.24 (d, 1H), 7.35 (m, 2H), 7.57 (m, 2H), 7.72 (f, 1H), 7.87 (f, 1H), 8.01 (d, 1H), 8.25 (bs, 1H), 8.48 (s, 1H), 8.59 ( m, 1H), 9.87 (bs, 1H); Mass Spec. MH + 464. 5- (2-aminoefoxy) -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine used as an initial material is prepared by reacting ethinylamine and? / - [3-chloro-4- (pyridin-2-lmetoxy) phenyl] -5-fluoroquinazolin-4-amine, using a procedure analogous to that described in Example 1 for the preparation of? / - [3-chloro -4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (methylamino) ethoxy] quinazolin-4-amine, to give 5- (2-aminoethoxy) -? / - [3-chloro-4- ( pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine in 49% yield; NMR spectrum (DMSO-d6) 3.1 2 (í, 2H), 3.29 (2H darkened under water), 4.28 (t, 2H), 5.28 (s, 2H), 7.12 (d, 1 H), 7.21 (d, 1) H), 7.34 (m, 2H), 7.57 (d, 1 H), 7.71 (m, 2H), 7.87 (t, 1 H), 8.23 (d, 1 H), 8.51 (s, 1 H), 8.58 (d, 1 H); Mass Spectrum MH + 422. [7] W-. { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} qui-nazolin-5-yl) oxy] propyl} -? / - methylacetamide. Prepared by reacting acetic acid with? / - [3-chloro-4- (pyridin-2-ylmeyoxy) phenyl-5 - [(1) -1-methyl-2- (methylamino) ethoxy] quinazolin-4-amine (prepared as described in Example 2-3) to give the title product in 50% yield; NMR spectrum (CDCIr.) 1 .47 (d, 3H), 2.00 (s, 3H), 3.00 (s, 3H), 3.45 (m, 1 H), 3.93 (m, 1 H), 5.00 (m, 1 H), 5.25 (s, 2H), 6.98 (m, 2H), 7.40 (m, 1 H), 7.49 (m, 1 H), 7.59 (m, 2H), 7.70 (m, 1 H), 7.90 ( s, 1 H), 8.53 (s, 2H), 9.82 (bs, 1 H); Mass Spectrum MH + 492.5. Example 3 2-Hydroxy-W-methyl- / V-. { 2 - [(4- {3-methyl-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} Acetamide 2-Hydroxy -? / - [2- (. {4- [4-hydroxy-3-meitylanilino] quinazolin-5-yl} oxy) ethyl] -? / - methylacetamide (100 mg), hydrochloride Picolyl chloride (60 mg) and potassium carbonate (120 mg) are stirred in DMF (5 ml) to which 18-crown-6 (10 mg) is added. The reaction is stirred at ambient temperature for 2 days. The DMF is removed in vacuo, water (5 ml) is added and then the suspension is exfoliated with DCM (2x5 ml). The DCM fraction is purified by chromatography using 2.5-5% of 10: 1 DCM / methanol containing 0.5% ammonium (0.880) as eluent. The appropriate fractions are evaporated, and the residue is precipitated from DCM / diethyl ether to give the title product as a light yellow solid (28 mg, 23%); NMR spectrum (DMSO-d6, 100 ° C) 2.29 (s, 3H), 3.00 (s, 3H), 3.90 (t, 2H), 4.1 6 (s, 2H), 4.50 (í, 2H), 5.20 (í , 2H), 5.20 (s, 2H), 7.01 (d, 1 H), 7.16 (d, 1 H), 7.34 (d, 2H), 7.51 (m, 2H), 7.55 (d, 1 H), 7.79 (í, 1 H), 7.83 (id, 1 H), 8.41 (s, 1 H), 8.57 (d, 1 H), 9.62 (s, 1 H); Mass Spec. MH + 474. 2-Hydroxy -? / - [2- (. {4- [4-hydroxy-3-methylanilino] quinazolin-5-yl} oxy) ethyl] -? / - methylacetamide Use as initial material is prepared as follows: 4-Chloro-5-fluoroquinazoline (6.76 g) is dissolved in isopropanol (200 ml) and 4-amino-2-methylphenol (5.00 g) is added. The mixture is heated under reflux for 2 hours, causing a yellow solid to precipitate. The mixture is cooled to room temperature and the solid is collected by filtration. The solid is dissolved in a boiling mixture of methanol (500 ml) and water (1000 ml) to give a brown solution. With vigorous stirring, the solution is basified with aqueous ammonia (0.880, 10 ml), causing a light brown solid to precipitate. The mixture is concentrated in vacuo to such a volume that all the methanol has been removed, leaving the product as a suspension in aqueous solution. The suspension cools; The solid is collected by filtration, triturated with ethyl acetate and dried over cold P2O5 in a vacuum oven to give 2-methyl-4 - [(5-fluoroquinazolin-4-yl) amino] phenol as a light brown solid (8.1 8 g, 82%); Specimen NMR (DMSO-d6) 3.30 (s, 3H), 6.78 (d, 1 H), 7.28 (m, 2H), 7.38 (dd, 1 H), 7.57 (d, 1 H), 7.78 (m, 1) H), 8.43 (s, 1 H), 8.88 (d, 1 H), 9.22 (s, 1 H); Mass Spec. MH + 270. A solution of? / -methylaminoethanol (0.80 g) in DMA (5 ml) is added dropwise to a suspension of sodium hydride (60% dispersion in mineral oil, 0.43 g) in DMA (20). ml). The reaction is stirred for 30 minutes then 15-crown-5 (50 mg) is added, followed by 2-mephyl-4 - [(5-fluoroquinazoln-4-yl) amino] phenol (1.00 g). The reaction is heated to 1 1 0 ° C for 2.5 hours. The reaction is cooled, quenched with saturated ammonium chloride, and concentrated in vacuo. Saturated sodium bicarbonate solution is added causing precipitiation of a solid which is collected by filtration, rinsed with water and precipitated from ethyl acetate to give 2-meityl-4- (. {5- [2-methylamino) ethoxy] quinazolin -4-il} amino) phenol as a gray solid (0.60 g, 50%); NMR spectrum (DMSO-d6) 2.16 (s, 3H), 2.38 (s, 3H), 3.01 (t, 2H), 4.32 (t, 2H), 6.87 (d, 1 H), 7.07 (d, 1 H) , 7.18 (d, 1 H), 7.45 (d, 1 H), 7.65 (dd, 1 H), 7.66 (t, 1 H), 8.41 (s, 1 H), 1 0.36 (s, 1 H); Mass Spectrum MH + 325. A solution of glycolic acid (1000 mg) in DMF (2 ml) was added to gofa gase to a solution of 2-methyl-4- (. {5- [2- (methylamino) ethoxy] ] quinazolin-4-yl.} amino) phenol (400 mg) in DMF (4 ml) and the mixture is kept under sonication for 5 minutes. A solution of HATU (51 9 mg) in DMF (2 ml) is then added and the solution is stirred at room temperature for 16 hours, and then concentrated in vacuo. The residue is treated with water to precipitate a brown solid which is collected by filtration, and rinsed with water to give 2-hydroxy -? / - [2- (. {4- [4-hydroxy-3-methylanilino] quinazolin- 5-yl.} Oxy) ethyl] - / V-methylacetamide as a brown solid (406 mg, 86%); NMR spectrum (DMSO-d6) 2.15 (s, 3H), 2.94 (s, 3H), 3.87 (m, 2H), 4.04 (s, 2H), 4.48 (m, 2H), 6.81 (d, 1 H), 7.20 (dd, 1 H), 7.25 (d, 1 H), 7.35 (m, 2H), 7.92 (t, 1 H), 8.64 (s, 1 H), 9.46 (s, 1 H), 10.49 (s) , 1 HOUR); Mass Spec. MH + 383. EXAMPLE 4 Using an analogous procedure to that described in Example 3 4- (4-hydroxyanilino) -quinazoline appropriate is reacted with the appropriate compound of the formula Q-CH2-L1 to give the compounds shown in the Table 2 below, where Q1 is one specified in Table 2 and L1 is chloro or methanesulfonate as specified in the notes for Table 2.g.

Table 2 [1] 2-Hydroxy-? -methyl-? { 2 - [(4- {3-methyl-4- (pyrazin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} Acetamida. Prepared by reacting 2-hydroxy -? / - [2- (. {4- [4-hydroxy-3-methylanilino] quinazolin-5-yl.}. Oxy) eyl] - / V-methylacetamide and pyrazin-2 ilmethyl methanesulfonate to give the title product as a pale yellow solid in 34% yield; NMR spectrum (DMSO-d6, 100 ° C) 2.26 (s, 3H), 3.00 (s, 3H), 3.92 (t, 2H), 4.16 (s, 2H), 4.51 (t, 2H), 5.26 (s, 2H), 7.05 (d, 1 H), 7.16 (d, 1 H), 7.35 (d, 1 H), 7.52 (m, 2H), 7.69 (f, 1 H), 8.40 (s, 1 H), 8.60 (d, 1 H), 8.64 (d, 1 H), 8.81 (s, 1 H), 9.63 (s, 1 H); Mass Spectrum MH * 475. Pyrazin-2-ylmethyl methanesulfonate used as starting material is prepared as follows: Di- / so-propylethylamine (175 μl) and sulfonyl methane chloride (80 μl) are added dropwise to a solution of 2- (hydroxymethyl) -pyrazine (1.01 mg, prepared as described in Chemistry Anales 1 979, p899) in DCM (5 ml) at 0 ° C and the reaction is allowed to warm to ambient temperature and is agasa by 30 minutes. DCM is removed in vacuo and the residue is used without further purification. [2] 2-Hydroxy-f-methyl- / V-. { 2 - [(4-. {3-methyl-4- (1, 3-thiazol-4-ylmethoxy) anilnino} quinazolin-5-yl) oxy] ethyl} acetamide. Prepared by reacting 2-hydroxy -? / - [2- (. {4- [4-hydroxy-3-methylanilino] quinazolin-5-yl} oxy) ethyl] -? / - methylacetamide and hydrochloride 4- (chloromethyl) -thiazole to give the title product as a white solid in 20% yield; NMR spectrum (DMSO-d6, 100 ° C) 2.23 (s, 3H), 3.00 (s, 3H), 3.91 (t, 2H), 4.08 (s, 2H), 4.49 (t, 2H), 5.25 (s, 2H), 7.07 (d, 1 H), 7.16 (d, 1 H), 7.34 (d, 1 H), 7.50 (m, 2H), 7.68 (m, 2H), 8.41 (s, 1 H), 9.07 (d, 1 H), 9.63 (s, 1 H); Mass Spectrum MH + 480. [3] 2-Hydroxy -? (- methyl-) V- (2- { [4- (3-methyl-4 - [(5-methylisoxazol-3-yl) methoxy] anilino ) quinazolin-5-yl] oxy} ethyl) acetamide. Prepared by reacting 2-hydroxy -? / - [2- (. {4- [4-hydroxy-3-methylanilino] quinazolin-5-yl} oxy) efil] -? / - methylacetamide and 3- (chloromethyl) ) -5-methylisoxazole to give the title product as a pale gray solid in 30% yield; NMR spectrum (DMSO-d6, 100 ° C) 2.22 (s, 3H), 2.41 (s, 3H), 3.00 (s, 3H), 3.92 (t, 2H), 4.05 (s, 2H), 4.48 (f, 2H), 5.15 (s, 2H), 6.28 (s, 1H), 7.05 (d, 1H), 7.16 (d, 1H), 7.34 (d, 1H), 7.48 (m, 2H), 7.68 (f, 1H) ), 8.42 (s, 1H), 9.62 (s, 1H); Specter of Mass MH + 478. [4] W-. { (2R) -2 - [(4- {3-Chloro-4- (pyridin-2-ylmethoxy) anilino} quinozolin-5-yl) oxy] propyl} -2-methoxyacetamida.

Prepared by reacting? / - [(2R) -2- ( { 4- [3-chloro-4-hydroxyanilino] quinazolin-5-yl.}. Oxy) propyl] -2-methoxyacetamide and picolyl chloride hydrochloride 43% production; NMR spectrum (DMSO-d6) 1.19 (d, 3H), 3.10 (s, 3H), 3.21 (dt, 1H), 3.72 (m, 1H), 3.77 (s, 2H), 4.93 (m, 1H), 5.29 (s, 2H), 7.22 (d, 2H), 7.24 (d, 2H), 7.32 (d, 1H), 7.36 (dd, 1H), 7.58 (m, 2H), 7.71 (t, 1H), 7.86 (d, td, 1H), 8.15 (d, 1H), 8.19 (t, 1H), 8.47 (s, 1H), 8.59 (d, 1H), 9.97 (s, 1H); Mass Spectrum MH + 508.? / - [(2R) -2- ( { 4- [3-Chloro-4-hydroxyanilino] quinazolin-5-yl.}. Oxy) propyl] -2-methoxyacetamide used as material Initial preparation is as follows: (R) -1-amino-2-propanol is reacted with 2-chloro-4 - [(5-fluoroquinazolin-4-yl) amino] phenol (prepared as described in Example 4-4 , preparation of initial materials) using a process analogous to that described in Example 1 for the preparation of? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (methylamino) ethoxy ] quinazolin-4-amine to give 4- (. {5 - [(1R) -2-amino-1-methylethoxy] quinazolin-4-yl} amino) -2-chlorophenyl in 64% yield; NMR spectrum (DMSO-d6) 1.39 (d, 3H), 2.88-3.03 (m, 2H), 3.72-3.85 (m, 1H), 6.95 (d, 1H), 7.15 (d, 1H), 7.29 (d, 1H), 7.45-7.52 (m, 1H), 7.69 (t, 1 H), 8.05 (s, 1 H), 8.45 (s, 1 H); Mass Spectrum MH * 345. 4- ( {5 - [(1 R) -2-Amino-1-methylethoxy] quinazolin-4-yl}. Amino) -2-chlorophenol is reacted with methoxyacetic acid using a process analogous to that described in Example 3 (preparation of starting materials) to give / V - [(2R) -2- (. {4- [3-chloro-4-hydroxyanilino] quinazolin-5-yl}. oxy) propyl] -2-mexoxyacefamide in 83% production; Specimen NMR (DMSO-d6) 1.4 (d, 3H), 3.1 (s, 3H), 3.35-3.45 (m, 1 H), 3.72-3.85 (m, 3H), 4.95-5.05 (m, 1 H) ), 7.05 (d, 1 H), 7.31 (d, 1 H), 7.4 (dd, 1 H), 7.48 (d, 1 H), 7.81 (m, 1 H), 7.95 (t, 1 H), 8.25 (t, 1 H), 8.8 (s, 1 H), 1 0.39 (s, 1 H). 1 0.74 (s, 1 H); Specter of Mass MH * 417. [5] W-. { 2 - [(4-. {3-Chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy- / V-methylacetamide. Prepared by reacting picolyl chloride hydrochloride and? / - [2- (. {4- [3-chloro-4-hydroxyanilino] quinazolin-5-yl.} Oxy) eyl] -2-hydroxy -? / - meyilacetamide in 66% production; Specimen NMR (DMSO-d6) 2.96 (s, 3H), 3.91 (í, 2H), 4.04 (d, 2H), 4.26 (t, 1 H), 4.40 (t, 2H), 5.28 (s, 2H), 7.14 (d, 1 H), 7.22 (d, 1 H), 7.32 (d, 1 H), 7.35 (m, 1 H), 7.57 (m, 2 H), 7.70 (m, 1 H), 7.86 (m , 1 H), 7.95 (s, 1 H), 8.42 (s, 1 H), 8.58 (d, 1 H), 9.73 (bs, 1 H); Mass Spectrum MH + 494.? / - [2- ( { 4 - [(3-Chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.}. Oxy) ethyl] -2-hydroxy -? / - Methylaceaemide used as initial material is prepared as follows: 4-Chloro-5-fluoro-quinazoline is reacted with 4-amino-2-chlorophenol using a process analogous to that described in Example 3 for the preparation of 2-meylyl-4 - [( 5-fluoroquinazolin-4-yl) amino] phenol, to give 2-chloro-4 - [(5-fluoroquinazolin-4-yl) amino] phenol in 85% yield; NMR spectrum (DMSO-d6) 6.97 (d, 1 H), 7.38 (dd, 1 H), 7.42 (dd, 1 H), 7.59 (d, 1 H), 7.73 (d, 1 H), 7.81 (dd) , 1 H), 8.51 (s, 1 H), 9.03 (d, 1 H), 1 0.07 (bs, 1 H); Mass Spectrum MH * 290. 2-Chloro-4 - [(5-fluoroquinazolin-4-yl) amino] phenol is reacted with? / - methylaminoethanol using a process analogous to that described in Example 3 for the preparation of 2- methyl-4- (. {5- [2- (methylamino) ethoxy] quinazolin-4-yl} amino) phenol, to give 2-chloro-4- (. {5- [2- (methylamino)] ethoxy] quinazolin-4-yl.}. amino) phenol in 96% yield; NMR spectrum (DMSO-d6) 2.41 (s, 3H), 3.05 (t, 2H), 4.36 (t, 2H), 6.97 (d, 1 H), 7.12 (d, 1 H), 7.31 (d, 1 H) ), 7.63 (1 H, dd), 7.70 (t, 1 H), 7.96 (s, 1 H), 8.47 (s, 1 H), 10.47 (bs, 1 H); Mass Spectrum MH * 345. 2-Chloro-4- (. {5- [2- (methylamino) eioxy] quinazolin-4-yl.}. Amino) phenol is reacted with glycolic acid using an analogous procedure to that described in Example 3 to give? / - [2- ( { 4- [3-Chloro-4-hydroxyanilino] quinazolin-5-yl.}. oxy) ethyl] -2-hydroxy -? / - mephilaceiamide in 58% production; NMR spectrum (DMSO-d6) 2.96 (s, 3H), 3.90 (t, 2H), 4.05 (m, 3H), 4.41 (t, 2H), 6.97 (d, 1 H), 7.14 (d, 1 H) , 7.34 (m, 2H), 7.70 (t, 1 H), 7.79 (d, 1 H), 8.40 (s, 1 H), 9.64 (s, 1 H), 10.00 (bs, 1 H); Mass Spectrum MH * 403. [6]? F- (2- { [4- (3-Chloro-4 - [(3-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy} ethyl ) -2-hydroxy- / V-methylacetamide. ? - [2- (. {4- [3-Chloro-4-hydroxyanilino] quinazolin-5-yl.}. Oxy) eyl] -2-hydroxy- / V -methylazef amide to give the product of the tíulo in 59% production; NMR spectrum (DMSO- d6 at 1 00 ° C) 2.91 (s, 3H), 3.83 (t, 2H), 3.99 (bs, 3H), 4.42 (í, 3H), 5.17 (s, 2H), 7.00-7.30 (m, 6H), 7.36 (m, 1 H), 7.50 (dd, 1 H), 7.63 (t, 1 H), 7.89 (d, 1 H), 8.38 (s, 1 H), 9.62 (bs, 1 HOUR); Mass Spectrum MH * 51 1. [7] iV-. { 2 - [(4-. {3-Chloro-4- (1, 3-thiazol-4-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy -? / - methylacetamide. Prepared by reacting 4- (chloromethyl) -1,3-thiazole and? / - [2- (. {4- [3-chloro-4-hydroxyanilino] quinazolin-5-yl.} Oxy] ethyl] hydrochloride] -2-hydroxy -? / - methylacelamide to give the production of the title in 54% yield; NMR spectrum (DMSO-d6 at 1 00 ° C) 2.99 (s, 3H), 3.91 (t, 2H), 4.07 (bs, 3H), 4.50 (t, 2H), 5.34 (s, 2H), 7.17 (d , 1 H), 7.30 (d, 1 H), 7.36 (d, 1 H), 7.59 (dd, 1 H), 7.72 (m, 2 H), 7.96 (d, 1 H), 8.46 (s, 1 H) ), 9.08 (d, 1 H), 9.70 (bs, 1 H); Mass Spec. MH * 500. [8] W- (2- { [4- (3-Chloro-4 - [(6-methylpyridin-2-yl) ethoxy] anilino) quinazolin-5-yl] oxy}, ethyl) -2-hydroxy -? / - rnetiIacetamide. A mixture of methanesulfonyl chloride (0.034 ml), triethylamine (0.077 ml) and (6-methylpyridin-2-yl) methanol (44 mg) is stirred in DCM (10 ml) overnight. The solution is concentrated in vacuo and DMF (20 ml) is added, followed by the addition of? / - [2- (. {4- [3-chloro-4-hydroxyanilino] quinazolin-5-yl}. oxy) ethyl] -2-hydroxy-? / - methylaceaemide (125 mg) and pofasium carbonate (150 mg) and the mixture was stirred for 2 days. The solution is concentrated in vacuo and water (50 ml) is added and the mixture is extracted with DCM (60 ml). The extract is dried and concentrated in vacuo and the residue is purified by chromatography using DCM-1 0% mephanol (2M ammonium) to give the title compound as a white solid (99 mg, 54%).; NMR spectrum (DMSO-d6 at 100 ° C) 2.50 (s, obscured by DMSO), 2.99 (s, 3H), 3.92 (t, 2H), 4.06 (bs, 3H), 4.49 (t, 2H), 5.22 ( s, 2H), 7.13-7.26 (m, 3H), 7.37 (m, 2H), 7.57 (dd, 1H), 7.72 (m, 2H), 7.98 (d, 1H), 8.46 (s, 1H), 9.70 (bs, 1H); Mass Spectrum MH * 508. [9]? -. { 2 - [(4-. {3-Chloro-4- (pyrazin-2-ylmethoxy) anilino} quinazoIin-5-yl) oxy] ethyl} -2-hydroxy -? / - methylacetamide. Prepared by reacting pyrazin-2-ylmethyl sulfonate with? / - [2- (. {4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.} Oxy) ethyl] -2- hydroxy -? / - methylacetamide to give the title product in 60% yield; NMR spectrum (DMSO-d6 at 100 ° C) 2.99 (s, 3H), 3.91 (t, 2H), 4.07 (bs, 3H), 4.49 (t, 2H), 5.37 (s, 2H), 7.17 (d, 1H), 7.29 (d, 1H), 7.36 (d, 1H), 7.60 (dd, 1H), 7.72 (t, 1H), 7.99 (d, 1H), 8.46 (s, 1H), 8.64 (m, 2H) ), 8.50 (s, 1H), 9.72 (bs, 1H); Mass Spec. MH * 495. [10]? M (2R) -2 - [(4. {3-Chloro-4- (pyridin-2-ylmethoxy) anilino}. Quinazolin-5-yl) oxy] propyl} acetamide. Prepared by reacting? / - [(2R) -2- ( { 4- [3-chloro-4-hydroxyanilino] quinazolin-5-yl.}. Oxy) propyl] acetamide and picolyl chloride hydrochloride in 76% yield; NMR spectrum (DMSO-d6) 1.40 (d, 3H), 1.78 (s, 3H), 3.39 (m, 1H), 3.62 (m, 1H), 4.87 (m, 1H), 5.29 (s, 2H), 7.21 -7.40 (m, 4H), 7.57 (m, 2H), 7.71 (t, 1H), 7.87 (m, 1H), 8.12 (d, 1H), 8.22 (t, 1H), 8.49 (s, 1H), 8.58 (d, 1H), 10.00 (bs, 1H); Mass Spectrum MH * 478.? / - [(2R) -2- ( { 4- [3-chloro-4-hydroxyanilino] quinazoIin-5-yl.}. Oxy) propyl] aceylamide used as starting material prepare by reacting 4- (. {5 - [(1R) -2-amino-1-methylethoxy] quinazolin-4-yl} amino) -2-chlorophenol (prepared as described in Example 4-4) with acetic acid using a procedure analogous to that described in Example 3 for the preparation of 2-hydroxy -? / - methyl -? / -. { 2 - [(4- ({3-methyl-4- (pyridin-2-yl methoxy) anilino} quinazolin-5-yl) oxy] ethyl} acef amide, to give? / - [(2R) -2- (. {4- [3-chloro-4-hydroxyanilino] quinazolin-5-yl} oxy) propyl] acetamide in 28% yield; NMR spectrum (DMSO-d6) 1.40 (d, 3H), 1.78 (s, 1H), 3.40 (m, 1H), 3.62 (m, 1H), 4.87 (m, 1H), 6.99 (d, 1H), 7.23 (d, 1H), 7.31 (d, 1H), 7.41 (dd, 1H), 7.71 (t, 1H), 7.97 (d, 1H), 8.22 (t, 1H), 7.49 (s, 1H), 9.99 ( s, 1H), 10.02 (s, 1H); Mass Spectrum MH * 387. [11] / V-. { (2rt) -2 - [(4. {3-Chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} -2-hydroxy- / -acetamide. Prepared by reacting? / - [(2R) -2- ( { 4- [3-chloro-4-hydroxyanilino] quinazolin-5-yl.}. Oxy) propyl] -2-hydroxy-? / - meyilaceia It gives picolyl chloride hydrochloride in 61% yield; NMR spectrum (DMSO-d6 at 100 ° C) 1.44 (d, 3H), 2.99 (s, 3H), 3.51 (m, 1H), 4.07 (m, 2H), 4.13 (m, 1H), 5.12 (m, 1H), 5.28 (s, 2H), 7.23 (m, 2H), 7.34 (m, 1H), 7.60 (m, 2H), 7.70 (t, 1H), 7.85 (t, 1H), 8.08 (d, 1H) ), 8.47 (s, 1H), 8.58 (bd, 1H), 9.87 (bs, 1H); Mass Spectrum MH * 508.? / - [(2R) -2- ( { 4- [3-Chloro-4-hydroxyanilino] quinazolin-5-yl.}. Oxy) propyl] -2-hydroxy-? / -methylacetamide used as an initial material is prepared as follows: 2-chloro-4-. { (5-fluoroquinazolin-4-yl) amino] phenol (2 g) is added to a stirred solution of (2R) -1- [allyl (methyl) amino] propan-2-oI (2.24 g, prepared as described in Example 2-3) in DMA (100 ml) and sodium hydride (60% dispersion in oil, 692 mg), and the mixture was heated at 110 ° C for 16 hours. The mixture is concentrated in vacuo then a saturated solution of sodium bicarbonate (200 ml) is added and extracted with DCM (300 ml). The extract is rinsed with brine, dried and concentrated in vacuo and the residue purified by chromatography using DCM-10% methanol / 2N ammonium as eluyenfe to give 4 - [(5 { (1R) -2- [aIil (methyl) amino] -1-methylethoxy!. quinozin-4-yl) amino] -2-chlorophenol as a yellow solid (1.88 g, 68%); NMR spectrum (DMSO-d6) 1.43 (d, 3H), 2.17 (s, 3H), 2.54 (dd, 1H), 2.97 (m, 3H), 4.94 (m, 1H), 5.00 (dd, 1H), 5.10 (dd, 1H), 5.63 (m, 1H), 6.98 (d, 1H), 7.18 (d, 1H), 7.29 (d, 1H), 7.42 (dd, 1H), 7.69 (t, 1H), 7.84 ( d, 1H), 8.44 (s, 1H), 10.01 (bs, 1H), 10.26 (s, 1H); Mass Spec. MH * 399. Chlorofris (rhiphenylphosphine) rhodium (!) (40 mg) is added to a solution of 4 - [(5- {(1R) -2- [allyl (methyl) amino] -1- mephyletoxy.} quinazolin-4-yl) amino] -2-chlorophenol (841 mg) in acetonitrile / water (5: 1.4 ml), and the mixture is heated at 130 ° C for 10 minutes by microwave irradiation. The cold mixture is subjected to ion exchange chromatography and product eluted with methanol / 2M ammonium yielding 2-chloro-4- (. {5 - [(1R) -1-mephol-2- (meitylamino) -ioxy]] quinazolin-4-yl.} amino) phenol as a brown solid (776 mg, 100%); NMR spectrum (DMSO-d6) 1.40 (d, 3H), 2.33 (s, 3H), 2.87 (m, 2H), 3.29 (1H obscured by water), 4.88 (m, 1H), 6.97 (d, 1H), 7.14 (d, 1H), 7.28 (d, 1H), 7.55 (dd, 1H), 7.68 (t, 1H), 7.95 (d, 1H), 8.45 (s, 1H), 10.51 (bs, 1H); Mass Spectrum MH * 359.? / - [(2R) -2- ( { 4 - [(3-Chloro-4-hydroxyphenyl) amino] quinazolin-5-yl}. Oxy) propyl] -2- hydroxy -? / - meitylacetamide used as starting material is prepared by reacting 2-chloro-4- (. {5 - [(1 R) -1-methyl-2- (methylamino) efoxy] quinazolin-4-yl}. amino) phenol with and glycolic acid using a procedure analogous to that described in Example 3 for the preparation of 2-hydroxy -? / - [2 (. {4- [4-hydroxy-3-methylanilino] quinazolin-5 -yl.}. oxy) ethyl] -? / - mefilaceiamide, to give N - [(2R) -2- (. {4- [3-chloro-4-hydroxyanilino] quinazolin-5-yl.} oxy] ) propyl] -2-hydroxy -? / - methylaceaemide in 57% yield; NMR spectrum (DMSO-d6) 1 .39 (d, 3H), 2.91 (m, 1 H), 2.97 (s, 3H), 3.39 (dd, 1 H), 4.04 (d, 2H), 4.16 (m, 1 H), 4.39 (m, 1 H), 5.08 (m, 1 H), 6.98 (d, 1 H), 7.27 (m, 2 H), 7.47 (dd, 1 H), 7.70 (t, 1 H) , 7.97 (d, 1 H), 8.43 (s, 1 H), 9.85 (s, 1 H), 9.99 (bs, 1 H); Mass Spectrum MH * 417. [12] / V-. { (2R) -2 - [(4- {3-Chloro-4- (pyrazin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} -2-hydroxy-? -acetylamide. Prepared by reacting pyrazin-2-ylmethyl sulfonate and? / - [(2R) -2- (. {4- [3-chloro-4-hydroxyanilino] quinazolin-5-yl.}. Oxy) propyl] -2 -hydroxy -? / - methylacetamide to give the product of the tíulo in 20% production; Specimen NMR (DMSO-d6) 1 .41 (d, 3H), 2.98 (s, 3H), 3.42 (dd, 1 H), 4.06 (m, 2H), 4.23 (m, 1 H), 4.41 (m, 1 H), 5.12 (m, 1 H), 5.39 (s, 2H), 7.25-7.38 (m, 3H), 7.72 (m, 2H), 8.15 (d, 1 H), 8.48 (s, 1 H) , 8.68 (d, 2H), 8.87 (s, 1 H), 9.96 (s, 1 H); Mass Spec. MH * 509. [13] iV - ((2fl) -2- { [4- (3-Chloro-4 - [(6-methylpyridin-2-yl) methoxy] anilino) quinazolin- 5-yl] oxy}. Propyl) -2-hydroxy- / V-methylacetamide. Prepared by reacting (6-methylpyridin-2-yl) melanol with? / - [(2R) -2- (. {4- [3-chloro-4-hydroxyanilino] quinazolin-5-yl.} oxi) propyl] -2-hydroxy-β-methylacetamide, using an analogous procedure to that described in Example 4-8 (in situ formation of (6-methylpyridin-2-yl) methyl methanesulfonate), to give the product of the product in 48% production; Specimen NMR (DMSO-d6) 1.40 (d, 3H), 2.50 (3H obscured by DMSO), 2.98 (s, 3H), 3.37 (dd, 1H), 4.06 (d, 1H), 4.22 (m, 1H), 4.41 (t, 1H), 5.10 (m, 1H), 5.26 (s, 2H), 7.20-7.30 (m, 3H), 7.33 (d, 1H), 7.37 (d, 1H), 7.67 (dd, 1H) 7.70-7.80 (m, 2H), 8.15 (d, 1H), 8.48 (s, 1H), 9.95 (s, 1H); Mass Spec. MH * 522. [14]? F - ((2R) -2- { [4- (3-Chloro-4 - [(3-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy .}. propyl) -2-hydroxy- / V-methylacetamide. Prepared by reacting 1- (chloromethyl) -3-fluo stearin and? / - [(2R) -2- (. {4- [3-chloro-4-hydroxyanilino] quinozolin-5-yl.}. oxy) propyl] -2-hydroxy -? / - mephilaceiamide to give the title product in 61% yield; NMR spectrum (DMSO-d6) 1.40 (d, 3H), 2.98 (s, 3H), 3.37 (dd, 1H), 4.06 (d, 2H), 4.22 (m, 1H), 4.41 (t, 1H), 5.11 (m, 1H), 5.28 (s, 2H), 7.19 (m, 1H), 7.22-7.38 (m, 5H), 7.47 (m, 1H), 7.68 (dd, 1H), 7.72 (t, 1H), 8.13 (d, 1H), 8.48 (s, 1H), 9.94 (s, 1H); Mass Spectrum MH * 525. [15]? R-. { (2R) -2 - [(4- {3-Chloro-4- (1,3-thiazol-4-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} -2-hydroxy- / V-methylacetamide. Prepared by reacting 4- (chloromethyl) -1,3-thiazole hydrochloride and? / - [(2R) -2- (. {4 - [(3-chloro-4-hydroxyanilino] quinazolin-5-yl.} oxi) propyl] -2-hydroxy -? / - methylacetamide to give the title product in 61% yield: NMR spectrum (DMSO-d6) 1.41 (d, 3H), 2.98 (s, 3H), 3.38 (dd, 1H), 4.06 (d, 2H), 4.22 (m, 1 H), 4.42 (t, 1 H), 5.1 1 (m, 1 H), 5.34 (s, 2H), 7.28 (d, 1 H), 7.34 (m, 2H), 7.69 (dd, 1 H), 7.73 (t, 1 H), 7.82 (s, 1 H), 8.12 (d, 1 H), 8.48 (s, 1 H), 9.18 (d) , 1 H), 9.95 (s, 1 H); Mass Spectrum MH * 514. [16] W- (2- { [4- (3-Chloro-4 - [(6-methy1pyridin-2-yl ) methoxy] aniIino) quinazolin-5-yl] oxy} ethyl) -2-hydroxy-methylacetamide Prepared by reacting (6-methylpyridin-2-yl) methanol and? / - [2- (. {4 - [3-Chloro-4-hydroxyanilino] quinazolin-5-yl.}. Oxy) ethyl] -? / - methylacetylamide using the procedure described in Example 4-8 (in situ formation of (6-methylpyridin-2-yl) ) methyl methanesulfonate), to give the title product in 67% yield; NMR spectrum (DMSO-d6) 1.94 (s, 3H), 3.06 (s, 3H), 3.27 (s, 3H), 3.84-3.96 (m, 2H), 4.35-4.45 (m, 2H), 5.24 ( s, 2H), 7.16 (d, 1H), 7.20-7.27 (m, 2H), 7.32-7.40 (m, 2H), 7.58 (dd, 1 H), 7.70-7.79 (m, 2H), 7.92 (d, 1 H), 8.45 (s, 1 H), 9.74 (s, 1 H); Mass Spectrum MH * 492.? / - [2- ( { 4- [3-chloro-4-hydroxyanilino] quinazolin-5-yl.}. Oxy) ethyl] -? / - methylacetamide used as starting material prepare as follows: Acetic acid is reacted with 2-chloro-4- (. {5- [2- (methylamino) ethoxy] quinazolin-4-yl} amino) phenol (prepared as described in Example 4- 5, preparation of starting materials) using a procedure analogous to that described in Example 3 for the preparation of 2-hydroxy -? / - [2- (. {4- [4-hydroxy-3-methylanilino] quinazoline-5 -yl.} oxy) ethyl] -? / - methylacetamide, to give the title product in 56% yield; NMR spectrum (DMSO-d6) 1.96 (s, 3H), 2.48 (s, 3H), 3.84 (m, 2H), 4.36 (t, 2H), 6.96 (d, 1 H), 7.14 (d, 1) H), 7.32 (m, 2H), 7.70 (m, 2H), 8.40 (s, 1 H), 9.62 (bs, 1 H), 1 0.01 (bs, 1 H); Mass Spectrum MH * 370. [17] W- (2- { [4- (3-Chloro-4 - [(2-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy} ethyl) -W-methylacetamide. Prepared by reacting 2-fluorobenzyl chloride with? / - [2- (. {4 - [(3-chloro-4-hydroxyanilino] quinazolin-5-yl.} Oxy) ethyl] -? / - methylacetamide, for give the title product in 71% production; NMR spectrum (DMSO-d6) 1.94 (s, 3H), 3.05 (s, 3H), 3.89 (t, 2H), 4.40 (t, 2H), 5.27 (s) , 2H), 7.17 (d, 1 H), 7.22-7.39 (m, 4H), 7.41 -7.48 (m, 1 H), 7.56-7.65 (m, 2H), 7.73 (dd, 1 H), 7.90 ( d, 1 H), 8.44 (s 1 H) 9.74 (s 1 H): Mass Spectrum MH * 495. [18]? f- (2- { [4- (3-Chloro-4 - [(3-fluorobenzyl) oxy] anilino) quinazolin-5-yl] ox?) Ethyl) -N-methylacetamide. Prepared by reacting 3-fluorobenzyl chloride and? / - [2- (. {4- [3-chloro-4-hydroxyanilino] quinazolin-5-yl.} Oxy) etiI] -N- to give the product of the title in 80% production; NMR spectrum (DMSO-d6) 1.94 and 1.97 (each s, together 3H), 2.90 and 3.05 (each s, together 3H), 3.89 and 3.91 (each t, June 2H), 4.40 and 4.55 (each f , together 2H), 5.27 (s, 2H), 7.14-7.27 (m, 3H), 7.29-7.39 (m, 3H), 7.45-7.51 (m, 1 H), 7.53-7.60 (m, 1 H), 7.73 and 7.76 (each t, together 1 H), 7.91 and 8.04 (each d, together 1 H), 8.45 and 8.50 (each s, June 1 H), 9.73 and 9.77 (each s, together 1 H): Spectrum of Mass MH * 495. [19] W-. { 2 - [(4-. {3-Chloro-4- (1, 3-thiazol-4-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} -? / - methylacetamide. Prepared by reacting 4- (chloromethyl) -l, 3-thiazole and? / - [2- (. {4- [3-chloro-4-hydroxyanilino] quinazolin-5-yl} oxy} ethyl] - ? / - methylacetamide to give the title product in 67% yield; NMR spectrum (DMSO-d6) 1.94 and 1.96 (each s, together 3H), 2.90 and 3.05 (each s, together 3H), 3.89 and 3.92 (each t, together 2H), 4.40 and 4.55 (each t , June 2H), 5.35 (s, 2H), 7.16 and 7.24 (each d, together 1 H), 7.34 and 7.37 (each d, together 2H), 7.56 and 7.59 (each dd, together 1 H), 7.73 and 7.76 (each t, together 1 H), 7.83 (s, 1 H), 7.90 and 8.02 (each d, together 1 H), 8.44 and 8.50 (each s, together 1 H), 9.16 (d, 1 H) , 9.73 and 9.76 (each s, June 1 H); Mass Spectrum MH * 484. [20] / V-. { 2 - [(4-. {3-Chloro-4- (pyrazin-2-ylmethoxy) anilino} quinazoIin-5-yl) oxy] ethyl} - -methylacetamide. Prepared by reacting pyrazin-2-ylmethyl methanesulfonate (prepared as described in Example 4-1, preparation of starting materials) and? / - [2- (. {4- [3-chloro-4-hydroxyaniino] quinazolin- 5-yl.} Oxy) ethyl] -? I-methylacetamide, to give the title product in 60% yield; NMR spectrum (DMSO-d6) 1.94 and 1.96 (each s, together 3H), 2.90 and 3.05 (each s, together 3H), 3.89 and 3.92 (each t, together 2H), 4.40 and 4.55 (each t , together 2H), 5.40 (s, 2H), 7.16 and 7.24 (each d, together 1 H), 7.29-7.39 (m, 2H), 7.58 and 7.60 (each dd, together 1 H), 7.73 and 7.76 (each t, together 1 H), 7.93 and 8.05 (each d, together 1 H), 8.44 and 8.51 (each s, together 1 H), 8.68 (d, 1 H), 8.69 (d, 1 H), 8.87 (s , 1 H), 9.74 and 9.77 (each s, together 1 H); Specter of Mass MH * 479. [21]? R-. { (2R) -2 - [(4- {3-Chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} -2-hydroxy acetamide.

Prepared by reacting? / - [(2R) -2- ( { 4- [3-chloro-4-hydroxyanilino] quinazolin-5-yl.}. Oxy) propyl] -2-hydroxyacetylamide and picolyl chloride hydrochloride to give the production of the product in 61% production; NMR spectrum (DMSO-d6) 1 .39 (d, 3H), 3.45-3.47 (m, 1 H), 3.70-3.83 (m, 3H), 4.86-4.99 (m, 1 H), 5.29 (s, 2H) ), 5.48 (t, 1 H), 7.20-7.27 (m, 2H), 7.28-7.39 (m, 2H), 7.54-7.64 (m, 2H), 7.71 (t, 1H), 7.87 (t, 1H) , 8.11-8.21 (m, 2H), 8.48 (s, 1H), 8.59 (d, 1H), 9.98 (s, 1H); Mass Spectrum MH * 494.? / - [(2R) -2- ( { 4- [3-Chloro-4-hydroxyanilino] quinazolin-5-yl.}. Oxy) propyl] -2-hydroxyaceiamide used as The initial material is prepared as follows: 4- ( {5 - [(1R) -2-amino-1-methylethoxy] quinazolin-4-yl}. amino) -2-chlorophenol ((prepared as described in Example 4-4, preparation of starting materials) is reacted with glycolic acid using a procedure analogous to that used in Example 1 for the preparation of? / -. {2 - [(4-. {3-Chloro-4 - (pyridin-2-ylmehoxy) anilino} quinazolin-5-yl) oxy] ethyl] -? / - methylacefamide, to give the title product in 61% yield: NMR specimen (DMSO-d6) 1.39 ( d, 3H), 3.70-3.80 (m, 3H), 4.90-4.97 (m, 1H), 7.0 (d, 1H), 7.26-7.31 (m, 2H), 7.41 (dd, 1H), 7.75 (t, 1H), 7.92 (d, 1H), 8.16 (t, 1H) 8.53 (s, 1H), 10.09 (s, 1H), 10.15 (s, 1H); Mass Spectrum MH * 403. Example 5 W-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - ethylacetamide ? - [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2-ethylamino) ethoxy] quinazolin-4-amine (58 mg) in DCM (3 ml) is treated with acetyl chloride (1 5 mg) and DI PEA (39 mg) and stir overnight. The solution is purified by chromatography using DCM at 10% 7N ammonium in methanol in DCM to give after uration with diethyl ether? / -. { 2 - [(4- {[3-Cyoro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazoln-5-yl) oxy] ethyl} -? -f-ethylacef amide (39 mg, 61%); NMR spectrum (DMSO-d6) 1 .1 2 (t, 3H), 1.98 (s, 3H), 3.37-3.42 (m, 2H), 3.87 (t, 2H), 4.39 (t, 2H), 5.31 (s, 2H), 7.16 (d, 1 H), 7.22-7.28 (m, 1 H), 7.33-7.39 (m, 2H), 7.55-7.61 (m, 2H), 7.71-7.75 (m, 1 H) ), 7.87-7.91 (m, 1 H), 7.94 (d, 1 H), 8.45 (s, 1 H), 8.61 (d, 1 H), 9.80 (s, 1 H); Mass Spectrum MH * 492.? / - [3-Chloro-4- (pyridin-2-ylmeyoxy) phenyl] -5- [2-ethylamino) -ioxy] quinazolin-4-amine used as starting material is prepared as follows: Epylene glycol (1 50 ml) was brought with sodium hydride (60% in oil, 3.1 g) and the exoirm was condensed at approximately 1 0 ° C with a cold bath. / V- [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] -5-fluoroquinazolin-4-amine (obtained as described in Example 1, preparation of starting materials, 12 g) is added in small portions and the mixture was heated at 120 ° C for 1 hour. The paste is cooled, poured into water / saturated ammonium chloride (1.5 liters) and the solid is collected and dried to give 2 - [(4- {[3-chloro-4- (pyridin-2-ylmethoxy ) phenyl] amino.}. quinazolin-5-yl) oxy] ethanol (12.6 g, 95%); NMR spectrum (DMSO-d6) 3.89-3.98 (m, 2H), 4.33 (t, 2H), 5.27 (s, 2H), 5.37 (i, 1 H), 7.1 3 (d, 1 H), 7.23 (d , 1 H), 7.31 -7.38 (m, 2H), 7.57 (d, 1 H), 7.68-7.75 (m, 2H), 7.83-7.90 (m, 1 H), 8.26 (d, 1 H), 8.54 (s, 1 H), 8.58 (d, 1 H), 1 0.41 (s, 1 1 H); Mass Spectrum MH * 422. To an agitated solution of 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] ethanol (20 g) in DCM (200 ml) and THF (200 ml) is added ionic chloride (20 ml) at room temperature. The solution is then heated under reflux for 2 hours. The solution is cooled and the product is filtered to give 5- (2-chloroethoxy) -? / - [3-chloro-4- (pyridin-2-ylmehoxy) phenyl] quinazolin-4-amine as its hydrochloride salt (25). g, 98%); NMR spectrum (DMSO-d6) 4.20-4.40 (t, 2H), 4.60-4.80 (t, 2H), 5.40 (s, 2H), 7.20-7.60 (m, 3H), 7.60-7.80 (m, 3H), 7.90-8.1 0 (m, 3H), 8.60-8.70 (d, 1 H), 8.9 (s, 1 H), 1 0.65-10.83 (bs, 1 H); Mass Spectrum MH * 441. 5- (2-Chloroethoxy) -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine (0.400 g) and ethylamine (1.2 g) are heated at 50 ° C overnight and then the solution is purified by chromatography using 10% DCM 7N ammonium in methanol in DCM to give? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- ( ethylamino) ethoxy] quinazolin-4-amine; Mass Spectrum MH * 450. Example 6 W-. { 2 - [(4- {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} - / V-ethyl-2-hydroxyketamide The procedure described in Example 1 is repeated using glycolic acid and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (ethylamino) ethoxy] quinazolin-4-amine (obtained as described in Example 5, preparation of starting materials) to give the title compound in 70% yield; NMR spectrum (DMSO-d6) 1 .1 0 (f, 3H), 3.29-3.45 (m, 2H), 3.80-3.95 (m, 2H), 4.10 (s, 2H), 4.30-4.55 (m, 2H) , 4. 42 (t, 1 H), 5.30 (s, 2H), 7.18 (d, 1 H), 7.22 (d, 1 H), 7.30-7.40 (m, 2H), 7.60 (d, 2H), 7.70- 7.78 (m, 1 H), 7.82-7.92 (m, 1 H), 7.95 (s, 1 H), 8. 43 (s, 1 H), 8.60 (d, 1 H), 9.80 (s, 1 H); Mass Spectrum MH * 508. Example 7 Í-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} - / V-propylacetamide The procedure described in Example 5 is repeated using? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (propylamino) efoxy] quinazolin-4-amine and acetyl chloride for give the compound of the product in 70% yield; Specimen NMR (DMSO-d6) 0.82 (í, 3H), 1 .53-1 .59 (m, 2H), 1 .97 (s, 3H), 3.27 (s, 2H), 3.86 (í, 2H), 4.39 (t, 2H), 5.31 (s, 2H), 7.1 7 (d, 1 H), 7.25 (d, 1 H), 7.33-7.39 (m, 2H), 7.58-7.60 (m, 2H), 7.71 -7.75 (m, 1 H), 7.87-7.91 (m, 1 H), 7.95 (d, 1 H), 8.45 (s, 1 H), 8.60 (d, 1 H), 9.80 (s, 1 H); Mass Spec. MH * 506.? / - [3-Chloro-4- (pyridin-2-ylmehoxy) phenyl] -5- [2- (propylamino) ethoxy] quinazolin-4-amine used as starting material is prepared as described in Example 5 (preparation of starting materials) using 5- (2-chloroethoxy) -? / - [3-chloro-4- (pyridin-2-ylmehoxy) phenyl] quinazolin-4-amine (obtained as described in Example 5, preparation of initial materials) and propylamine; Mass Spec. MH * 464. Example 8 _V-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy- / V-propylacetamide The procedure described in Example 1 is repeated using glycolic acid and? / - [3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] -5- [2- (propylamino) -ioxy] quinazolin-4-amine (obtained as described in Example 7, preparation of initial materials) to give the title compound in 26% yield; Specimen NMR (DMSO-d6) 0.84 (t, 3H), 1.53-1.65 (m, 2H), 3.26 (t, 2H), 3.95 (t, 2H), 4.14 (d, 2H), 4.38 (t, 1H) , 4.47 (í, 2H), 4.53-4.58 (m, 1H), 5.36 (s, 1H), 7.24 (d, 1H), 7.31 (d, 1H), 7.39-7.44 (m, 2H), 7.63-7.67 (m, 2H), 7.76-7.81 (m, 1H), 7.92-7.96 (m, 1H), 8.05 (s, 1H), 8.51 (s, 1H), 8.66 (d, 1H), 9.87 (s, 1H) ); Mass Spectrum MH * 522. Example 9 and V-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - isopropylacetamide The procedure described in Example 5 is repeated using / V- [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (isopropylamino) ethoxy] quinazolin-4-amine and acetyl chloride for give the compound of the tífulo in 49% production; Specimen NMR (DMSO-d6) 1.19 (d, 6H), 2.07 (s, 3H), 3.77 (f, 2H), 4.06-4.14 (m, 1H), 4.34 (i, 2H), 5.31 (s, 2H) , 7.21 (d, 1H), 7.27 (d, 1H), 7.32-7.39 (m, 2H), 7.57-7.63 (m, 2H), 7.69-7.75 (m, 1H), 7.86-7.91 (m, 1H) , 8.01 (d, 1H), 8.46 (s, 1H), 8.60 (d, 1H), 10.00 (s, 1H); Mass Spectrum MH * 506.? / - [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (isopropylamino) -ioxy] quinazolin-4-amine used as starting material is prepared as described in Example 5 (preparation of starting materials) using 5- (2-chloroethoxy) -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine (obtained as described in Example 5, preparation of starting materials) and isopropylamine; Mass Spectrum M H * 464. Example 10? / -. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy- / V-isopropylacetamide The procedure described in Example 1 is repeated using glycolic acid and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (isopropylamino) efoxy] quinazolin-4-amine (obtained as described in Example 9, preparation of starting materials) to give the title compound in 11% yield; NMR spectrum (DMSO-d6) 1 .1 9 (d, 6H), 3.81 (t, 2H), 3.93-4.01 (m, 1 H), 4.14-4.18 (m, 2H), 4.35-4.47 (m, 3H) ), 5.31 (s, 2H), 7.21 -7.29 (m, 2H), 7.32-7.40 (m, 2H), 7.56-7.63 (m, 2H), 7.70-7.76 (m, 1 H), 7.86-7.91 ( m, 1 H), 8.04 (s, 1 H), 8.47 (s, 1 H), 8.60 (d, 1 H), 1 0.02 (s, 1 H); Mass Spec. MH * 522. Example 11 W-Alyl-W-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] etl} acetamide The procedure described in Example 5 is repeated using 5- [2- (al.lamino or) ethoxy] -? / - [3-chloro-4- (pyridin-2-ylmehoxy) phenyl] quinazolin-4-amine and chloride of acetyl to give the title compound in 47% yield; NMR spectrum (DMSO-d6) 1.95 (s, 3H), 3.86 (t, 2H), 4.02-4.06 (m, 2H), 4.38 (i, 2H), 5.07-5.18 (m, 2H), 5.31 ( s, 2H), 5.82-5.92 (m, 1 H), 7.14 (d, 1 H), 7.25 (d, 1 H), 7.32-7.40 (m, 2H), 7.55-7.61 (m, 2H), 7.70 -7.75 (m, 1 H), 7.86-7.93 (m, 2H), 8.44 (s, 1 H), 8.61 (d, 1 H), 9.76 (s, 1 H); Mass Spec. MH * 504. 5- [2- (Allylamino) ethoxy] -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyI] quinazolin-4-amine used as starting material is prepared as described in Example 5 (preparation of starting materials) using 5- (2-chloroethoxy) -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine (obtained as described in Example 5, preparation of starting materials) and allylamine; Mass Spec. MH * 462. Example 12?, - Allyl- / V-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxyacetamide The procedure described in Example 1 is repeated using glycolic acid and 5- [2- (allylamino) ethoxy] -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine (obtained as described in Example 1 1, preparation of initial materials) to give the title compound in 24% yield; NMR spectrum (DMSO-d6) 3.79-4.19 (m, 6H), 4.38-4.63 (m, 3H), 5.06-5.19 (m, 2H), 5.31 (s, 2H), 5.69-5.90 (m, 1) H), 7.16 (d, 1 H), 7.25 (d, 1 H), 7.33-7.39 (m, 2H), 7.56-7.63 (m, 2H), 7.70-7.76 (m, 1 H), 7.86-7.91 (m, 1 H), 7.98 (s, 1 H), 8.45 (s, 1 H), 8.61 (d, 1 H), 9.80 (s, 1 H); Mass Spectrum MH * 520. Example 13 W-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} - / V-cyclopropylacetamide The procedure described in Example 5 is repelled using? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (cyclopropylamino) ethoxy] quinazolin-4-amine and acyl chloride for give the title compose in 38% production; NMR spectrum (DMSO-d6) 0.76-0.82 (m, 4H), 2.06 (s, 3H), 2.76-7.83 (m, 1 H), 3.87 (t, 2H), 4.42 (i, 2H), 5.31 (s) , 2H), 7.1 9 (d, 1 H), 7.26 (d, 1 H), 7.32-7.40 (m, 2H), 7.56-7.61 (m, 2H), 7.70-7.75 (m, 1 H), 7.86 -7.92 (m, 1 H), 7.94-7.96 (m, 1 H), 8.45 (s, 1 H), 8.60 (d, 1 H), 9.76 (s, 1 H); Mass Spectrum MH * 504.? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (cyclopropyllamino) ethoxy] quinazolin-4-amine used as starting material is prepared as described in Example 5 (preparation of starting materials) by using 5- (2-chloroefoxy) -? / - [3-chloro-4- (pyridin-2-ylmehoxy) phenyl] quinazolin-4-amine (obtained as described in US Pat. Example 5, preparation of starting materials) and cyclopropanamine; Mass Spectrum M H * 462. Example 14? / -. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - cyclopropyl-2-hydroxyacetamide The procedure described in Example 1 is repelled using glycolic acid and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (cyclopropylamino) ethoxy] quinazolin-4-amine (obtained as described in Example 13, preparation of starting materials) to give the title compound in 19% yield; NMR spectrum (DMSO-d6) 0.73-0.80 (m, 4H), 2.73-2.80 (m, 1H), 3.90 (t, 2H), 4.24 (s, 3H), 4.44 (t, 2H), 5.31 (s, 2H), 7.20 (d, 1H), 7.25 (d, 1H), 7.35 (d, 1H), 7.36-7.40 (m, 1H), 7.57-7.62 (m, 2H), 7.71-7.76 (m, 1H) , 7.86-7.92 (m, 1H), 8.01 (d, 1H), 8.46 (s, 1H), 8.61 (d, 1H), 9.80 (s, 1H); Mass Spectrum MH * 520. Example 15 _V-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? f- (cyclopropymethyl) acetamide The procedure described in Example 5 is repeated using? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5-. { 2- [(cyclopropylmethyl) amino] ethoxy} quinazolin-4-amine and acetyl chloride to give the title compound in 58% yield; NMR spectrum (DMSO-d6) 0.16-0.27 (m, 2H), 0.36-0.52 (m, 2H), 0.97-1.06 (m, 1H), 2.00 (s, 3H), 3.24-3.29 (m, 2H), 3.93-4.02 (m, 2H), 4.33-4.56 (m, 2H), 5.31 (s, 2H), 7.13-7.18 (m, 1H), 7.21-7.29 (m, 1H), 7.31-7.40 (m, 2H) ), 7.54-7.62 (m, 2H), 7.69-7.79 (m, 1H), 7.86-7.92 (m, 1H), 7.63-7.96 (m, 1H), 8.44 (s, 1H), 8.61 (d, 1H) ), 9.81 (s, 1H); Mass Spectrum MH * 518. ? / - [3-Chloro-4- (pyridin-2-ylmeyoxy) phenyl] -5-. { 2 - [(cyclopropylmethyl) amino] ethoxy} quinazolin-4-amine used as starting material is prepared as described in Example 5 (preparation of initial materials) by using 5- (2-chloroefoxy) -? / - [3-chloro-4- (pyridin-2-ylmehoxy) phenyl] quinazolin-4-amine (obfenide as described in Example 5, preparation of initial materials) and (cyclopropylmethyl) amine; Mass Spectrum MH * 476. Example 16? Í-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? - (cyclopropylmethyl) -2-hydroxy acetamide The procedure described in Example 1 is repeated using glycolic acid and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5-. { 2 - [(Cyclopropylmethyl) amino] -ioxy} quinazolin-4-amine (obfenida as described in Example 1, preparation of starting materials) to give the title compound in 23% yield; NMR spectrum (DMSO-d6) -0.04-0.04 (m, 2H), 0.13-0.29 (m, 2H), 0.74-0.83 (m, 1 H), 2.98 (d, 1 H), 3.66-3.80 (m, 2H), 3.85-3.93 (m, 2H), 4.12-4.32 (m, 4H), 5.08 (s, 2H), 6.95 (d, 1 H), 7.02 (d, 1 H), 7.09-7.1 7 (m , 2H), 7.30-7.40 (m, 2H), 7.47-7.54 (m, 1 H), 7.63-7.68 (m, 1 H), 7.73-7.82 (m, 1 H), 8.21 -8.29 (m, 1 H), 8.37 (d, 1 H), 9.62 (s, 1 H); Mass Spectrum MH * 534.

Example 17? / -. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - cyclobutylacetamide The procedure described in Example 5 is repeated using? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (cyclobuylamino) -ioxy] quinazolin-4-amine and acetyl chloride for give the title compound in 42% yield; NMR spectrum (DMSO-d6) 1.50-1.65 (m, 2H), 2.01 (s, 3H), 2.12-2.21 (m, 4H), 3.94 (t, 2H), 4.28-4.38 (m, 3H) ), 5.31 (s, 2H), 7.19 (d, 1 H), 7.26 (d, 1 H), 7.32-7.40 (m, 2H), 7.57-7.62 (m, 2H), 7.69-7.76 (m, 1) H), 7.86-7.91 (m, 1 H), 7.97 (s, 1 H), 8.45 (s, 1 H), 8.60 (d, 1 H), 9.90 (s, 1 H); Mass Spectrum MH * 518.? / - [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (cyclobutylamino) ethoxy] quinazolin-4-amine used as starting material is prepared as described in Example 5 (preparation of starting materials) using 5- (2-chloroethoxy) -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine (obtained as described in Example 5, preparation of starting materials) and cyclobutanamine; Mass Spectrum M H * 476. Example 18? V-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} - / V-cicIobutil-2-hidroxiacetamida The procedure described in Example 1 is repeated using glycolic acid and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (cyclobutylamino) ethoxy] quinazolin-4-amine (obfenide as described in Example 17, preparation of starting materials) to give the compound of the product in 22% yield; Specimen NMR (DMSO-d6) 1.49-1.65 (m, 2H), 2.08-2.27 (m, 4H), 3.97 (s, 2H), 4.12 (d, 2H), 4.20-4.29 (m, 1H), 4.32- 4.43 (m, 3H), 5.31 (s, 2H), 7.21 (d, 1H), 7.26 (d, 1H), 7.33-7.40 (m, 2H), 7.57-7.63 (m, 2H), 7.71-7.76 ( m, 1H), 7.86-7.92 (m, 1H), 8.02 (s, 1H), 8.47 (s, 1H), 8.60 (d, 1H), 9.92 (s, 1H); Mass Spectrum MH * 534. Example 19 / V-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - (1-methylpiperidin-4-yl) acetamide The procedure described in Example 5 is repeated using? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5-. { 2 - [(1-methyl-piperidin-4-yl) amino] eloxi} quinazolin-4-amine and acetyl chloride to give the title compound in 41% yield; NMR spectrum (DMSO-d6) 1 .62-1 .90 (m, 4H), 2.09 (s, 3H), 2.15-2.43 (m, 4H), 2.79-3.13 (m, 3H), 3.76-3.83 (m , 2H), 3.86-3.92 (m, 1 H), 4.30-4.47 (m, 2H), 5.31 (s, 2H), 7.21 (d, 1 H), 7.26 (d, 1 H), 7.32-7.40 ( m, 2H), 7.57-7.61 (m, 2H), 7.69-7.75 (m, 1 H), 7.86-7.92 (m, 1 H), 7.98-8.00 (m, 1 H), 8.46 (s, 1 H) ), 8.61 (d, 1 H), 9.95 (s, 1 H); Mass Spectrum MH * 561. ? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5-. { 2 - [(1-methylpiperidin-4-yl) amino] ethoxy} quinazolin-4-amine used as starting material is prepared as described in Example 5 (preparation of starting materials) using 5- (2-chloroethoxy) -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine (obtained as described in Example 5, preparation of starting materials) and 1-methylpiperidin-4-amine; Mass Spectrum MH + 51 9. Example 20? Í-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? r- (tetrahydro-2H-pyran-4-yl) acetamide The procedure described in Example 5 is repeated using? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (teirahydro-2 - / - pyran-4-ylamino) -ioxy] quinazolin-4-amine and acetyl chloride to give the title compound in 68% yield; NMR spectrum (DMSO-d6) 1.49-1.71 (m, 2H), 1.75-1.98 (m, 2H), 2.1 1 (s, 3H), 3.36-3.45 (m, 2H), 3.78-3.96 (m, 5H), 4.26-4.46 (m, 2H), 5.31 (s, 2H), 7.22 (d, 1 H), 7.26 (d, 1 H), 7.33 (d, 1 H), 7.35 -7.40 (m, 1 H), 7.56-7.63 (m, 2H), 7.69-7.75 (m, 1 H), 7.86-7.91 (m, 1 H), 7.99-8.03 (m, 1 H), 8.46 ( m, 1 H), 8.61 (d, 1 H), 9.98 (s, 1 H); Mass Spectrum MH * 548.? / - [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (tetrahydro-2 H -pyran-4-ylamino) ethoxy] quinazolin-4-amine used as initial material is prepared as described in Example 5 (preparation of initial materials) using 5- (2-chloroethoxy) -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4 -amine (obfenida as described in Example 5, preparation of initial maferiales) and íetrahidro-2-pyran-4-amina; Mass Spectrum MH * 506. Example 21 ?? -. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy-? F- (tetrahydro-2H-pyran-4-yl) acetamide The procedure described in Example 1 is repeated using glycolic acid and? / - [3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] -5- [2- (tetrahydro-2H-pyran-4-ylamino) eioxy ] quinazolin-4-amine (obtained as described in Example 20, preparation of initial maferials) to give the title compound in 12% yield; NMR spectrum (DMSO-d6) 1.53-1.69 (m, 2H), 1.77-2.07 (m, 2H), 3.34-3.42 (m, 2H), 3.73-3.92 (m, 5H), 4.14-4.25 (m, 2H) ), 4.31-4.54 (m, 3H), 5.31 (s, 2H), 7.21-7.29 (m, 2H), 7.32-7.40 (m, 2H), 7.57-7.63 (m, 2H), 7.70-7.76 (m , 1H), 7.86-7.91 (m, 1H), 8.03 (s, 1H), 8.47 (s, 1H), 8.61 (d, 1H), 9,989 (s, 1H); Mass Spectrum MH * 564. Example 22 / V-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - (2-hydroxyethyl) acetamide The procedure described in Example 5 is repeated using 2- (. {2 - [(4- {[[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl. ) oxy] ethyl.} amino) efanol and acetyl chloride to give the title compound in 21% yield; NMR spectrum (DMSO-d6) 2.00 (s, 3H), 3.43 (t, 2H), 3.54-3.59 (m, 2H), 3.88-3.97 (m, 2H), 4.41 (t, 2H), 4.85 (t, 1H), 5.31 (s, 2H), 7.16 (d, 1H), 7.25 (d, 1H), 7.33 (d, 1H), 7.35-7.40 (m, 1H), 7.57-7.62 (m, 2H), 7.70 -7.75 (m, 1H), 7.86-7.92 (m, 1H), 7.96 (d, 1H), 8.45 (s, 1H), 8.61 (d, 1H), 9.83 (s, 1H); Mass Spectrum MH * 508. 2- ( {2 - [(4- { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} amino) ethanol used as starting material is prepared as described in Example 5 (preparation of starting materials) using 5- (2-chloroethoxy) -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4 -amine (obtained as described in Example 5, preparation of starting materials) and 2-aminoethanol; Mass Spectrum MH * 466. Example 23 / -. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy -? / - (2-hydroxyethyl) acetamide 2- ( {2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] etl.} Amino ) ethanol (obtained as described in Example 22, preparation of starting materials) (0.208 g) in DCM (10 ml) is treated with 2-chloro-2-oxoethyl acetate (0.091 g) and DIPEA (0.1 73 g) and stir for 30 minutes. 7N Ammonium in methanol (20 ml) is added and the solution stirred overnight. The mixture is evaporated and purified by chromatography using 8% DCM 7N ammonium in methanol in DCM to give the title compound in 30% yield; NMR spectrum (DMSO-d6) 3.37 (í, 2H), 3.56 (t, 2H), 3.95 (f, 2H), 4.1 1 -4.1 7 (m, 2H), 4.25 (t, 1 H), 4.44 (t , 2H), 4.91 (t, 1H), 5.31 (s, 2H), 7.17 (d, 1H), 7.25 (d, 1H), 7.32-7.40 (m, 2H), 7.59 (d, 2H), 7.70- 7.76 (m, 1H), 7.86-7.91 (m, 1H), 8.00 (d, 1H), 8.46 (s, 1H), 8.61 (d, 1H), 9.85 (s, 1H); Mass Spectrum MH * 524. Example 24 W-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} - / V- (2-methoxyethyl) acetamide The procedure described in Example 5 is repeated using? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5-. { 2 - [(2-methoxyethyl) amino] ethoxy} quinazolin-4-amine and acetyl chloride to give the title compound in 30% yield; NMR spectrum (DMSO-d6) 1.99 (s, 3H), 3.24 (s, 3H), 3.46-3.51 (m, 2H), 3.52-3.57 (m, 2H), 3.88-3.98 (m, 2H), 4.37- 4.43 (m, 2H), 5.31 (s, 2H), 7.17 (d, 1H), 7.26 (d, 1H), 7.34 (d, 1H), 7.35-7.40 (m, 1H), 7.55-7.63 (m, 2H), 7.71-7.78 (m, 1H), 7.86-7.92 (m, 1H), 7.94 (d, 1H), 8.46 (s, 1H), 8.61 (d, 1H), 9.86 (s, 1H): Spectrum of Mass MH * 522.? / - [3-Chloro-4- (pyridin-2-ylmeyoxy) phenyl] -5-. { 2 - [(2-methoxy-yl) amino] efoxy} quinazolin-4-amine used as initial material is prepared as described in Example 5 (preparation of initial materials) by using 5- (2-chloroethoxy) -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amino (obtained as described in Example 5, preparation of starting materials) and (2-mexoxyeyl) amine; Mass Spectrum MH * 480. Example 25 < V-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy- / V- (2-methoxyethyl) acetamide The procedure described in Example 1 is repeated using glycolic acid and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5-. { 2 - [(2-methoxyethyl) amino] ethoxy} quinazolin-4-amine (obtained as described in Example 24, preparation of starting materials) to give the title compound in 27% yield; NMR spectrum (DMSO-d6) 3.18 (s, 1H), 3.24 (s, 2H), 3.48 (s, 3H), 3.55-3.60 (m, 1H), 3.86-3.98 (m, 2H), 4.10-4.15 ( m, 2H), 4.32 (t, 1H), 4.43 (t, 1H), 4.51-4.57 (m, 1H), 5.31 (s, 2H), 7.17 (d, 1H), 7.25 (d, 1H), 7.33 -7.40 (m, 2H), 7.57-7.63 (m, 2H), 7.71-7.76 (m, 1H), 7.86-7.91 (m, 1H), 7.99-8.05 (m, 1H), 8.46 (s, 1H) 8.60 (d, 1H), 9.84 (s, 1H); Mass Spectrum MH * 538. Example 26 _V-. { 2 - [(4- {[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? f-prop-2-in-1-ylacetamide The procedure described in Example 5 is repeated using? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (prop. -2-in-1-ylamino) ethoxy] quinazolin-4-amine and acetyl chloride to give the title compound in 53% yield; Specimen NMR (DMSO-d6) 2.03 (s, 3H), 3.27 (s, 1 H), 3.93-4.04 (m, 2H), 4.24-4.32 (m, 2H), 4.43 (1, 1 H), 4.56- 4.63 (m, 1 H), 5.31 (s, 2H), 7.13 (d, 1 H), 7.25 (d, 1 H), 7.34 (d, 1 H), 7.35-7.41 (m, 1 H), 7.52 -7.63 (m, 2H), 7.70-7.79 (m, 1 H), 7.86-7.93 (m, 2H), 8.44 (s, 1 H), 8.61 (d, 1 H), 9.69 (s, 1 H); Mass Species MH * 502.? / - [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (prop-2-yn-1-ylamino) -ioxy] quinazolin-4-amine used as starting material is prepared as described in Example 5 (preparation of starting materials) using 5- (2-chloroethoxy) -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4 -amine (obtained as described in Example 5, preparation of starting materials) and prop-2-in-1 -amine; Mass Spectrum MH * 460. Example 27? Í'-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy-_V-prop-2-in-1-ylacetamide The procedure described in Example 1 is repeated using glycolic acid and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (prop-2-yn-1-ylamino) ethoxy] ] quinazolin-4-amine (obtained as described in Example 26, preparation of starting materials) to give the title compound in 26% yield; NMR spectrum (DMSO-d6) 3.98 (s, 2H), 4.16 (s, 2H), 4.28 (s, 2H), 4.47 (s, 1 H), 4.55-4.66 (m, 1 H), 5.31 (s, 2H), 7.12-7.21 (m, 1 H), 7.25 (d, 1 H), 7.32-7.40 (m, 2H), 7.59 (d, 2H), 7.70-7.78 (m, 1 H), 7.86-7.92 (m, 1 H), 7.97-8.06 (m, 1 H), 8.43-8.51 (m, 1 H), 8.61 (d, 1 H), 9.76 (s, 1 H); Mass Spectrum MH * 518. Example 28 W-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy-? -methylpropanamide The procedure described in Example 1 is repeated using 2-hydroxypropanoic acid and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (mephilamino) -ioxy] quinazolin-4-amine (obtained as described in Example 1, preparation of starting materials) to give the title compound in 56% yield; NMR spectrum (DMSO-d6) 1.08 (d, 3H), 3.11 (s, 3H), 3.82-4.12 (m, 2H), 4.36-4.47 (m, 3H), 4.52-4.72 (m, 1H), 5.31 ( s, 2H), 7.18 (d, 1H), 7.25 (d, 1H), 7.34 (d, 1H), 7.35-7.40 (m, 1H), 7.52-7.62 (m, 2H), 7.70-7.76 (m, 1H), 7.86-7.91 (m, 1H), 7.94-7.97 (m, 1H), 8.44 (s, 1H), 8.61 (d, 1H), 9.75 (s, 1H); Mass Spectrum MH * 508. Example 29 V-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? r-methyl-tetrahydrofuranyl-2-carboxamide The procedure described in Example 1 is repeated using tetrahydrofuran-2-carboxylic acid and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (methylamino) ethoxy] quinazoline-4 -amine (obtained as described in Example 1, preparation of starting materials) to give the title compound in 89% yield; Specimen NMR (DMSO-d6) 1.64-1.94 (m, 4H), 3.09 (s, 3H), 3.57-3.70 (m, 2H), 3.82-3.97 (m, 2H), 4.42 (i, 2H), 4.60- 4.66 (m, 1H), 5.31 (s, 2H), 7.16 (d, 1H), 7.23 (d, 1H) 7.33 (d, 1H), 7.35-7.39 (m, 1H), 7.52-7.57 (m, 1H) ), 7.59 (d, 1H), 7.70-7.75 (m, 1H), 7.85-7.91 (m, 1H), 7.92 (d, 1H), 8.42 (s, 1H), 8.61 (d, 1H), 9.70 ( s, 1 H); Mass Spectrum MH * 534. Example 30) V-. { 2 - [(4- { [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino.}. Quinazolin-5-iOoxythi -? ^ I-dimethylprolinamide The procedure described in Example 1 is repeated using 1-methylproline and? / - [3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] -5- [2- (methylamino) ethoxy] quinazolin-4-amine ( obtained as described in Example 1, preparation of starting materials) to give the title compound in 38% yield; NMR spectrum (DMSO-d6) 1.55-1.68 (m, 3H), 1.92-2.03 (m, 2H), 2.12 (s, 2H), 3.29 (s, 6H), 3.87-4.03 (m, 2H), 4.40- 4.61 (m, 2H), 5.31 (s, 3H), 7.17 (d, 1H), 7.22 (d, 1H), 7.33 (d, 1H), 7.35-7.39 (m, 1H), 7.57-7.63 (m, 2H), 7.69-7.75 (m, 1H), 7.86-7.91 (m, 1H), 8.05 (d, 1H), 8.43 (s, 1H), 8.60 (d, 1H), 9.76 (s, 1H); Mass Spectrum MH * 547. Example 31 W-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy -? /, 2-dimethylpropanamide The procedure described in Example 1 is repeated using 2-hydroxy-2-methylpropanoic acid and? / - [3-chloro-4- (pyrridin-2-ylmeloxy) phenyl] -5- [2- (mephilamino) ethoxy] quinazolin -4-amine (obtained as described in Example 1, preparation of starting materials) to give the compound of the product in 39% yield; Specimen NMR (DMSO-d6) 1 .20 (s, 6H), 3.34 (s, 3H), 3.89 (s, 2H), 4.43 (s, 2H), 5.27 (s, 1 H), 5.31 (s, 2H) ), 7.1 8 (d, 1 H), 7.24 (d, 1 H), 7.32-7.40 (m, 2H), 7.53-7.57 (m, 1 H), 7.58 (d, 1 H), 7.76-7.76 ( m, 1 H), 7.86-7.91 (m, 2H), 8.43 (s, 1 H), 8.59-8.61 (m, 1 H), 9.75 (s, 1 H); Mass Spectrum M H * 522. Example 32 N-. { 2 - [(4- {[3-C] -4- (pi-ridin-2-ylmethoxy) -fenyl] -ami no.} Quinazoli n-5-yl) oxy] ethyl} -1-h id roxi -iV-methylcyclo propan oca rboxam ida The procedure described in Example 1 is repeated using 1-hydroxycyclopropanecarboxylic acid and / V- [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (methylamino) efoxy] quinazolin-4-amine (obtained as described in Example 1, preparation of initial materials) to yield the title compound in 54% yield; Specimen NMR (DMSO-d6) 0.68-0.80 (m, 4H), 3.30 (s, 3H), 3.84-3.96 (m, 2H), 4.37-4.49 (m, 2H), 5.31 (s, 2H), 6.16- 6.23 (m, 1H), 7.14-7.21 (m, 1H), 7.24 (d, 1H), 7.32-7.40 (m, 2H), 7.51-7.56 (m, 1H), 7.59 (d, 1H), 7.71- 7.76 (m, 1H), 7.86-7.91 (m, 2H), 8.40-8.47 (m, 1H), 8.61 (d, 1H), 9.68-9.75 (m, 1H); Mass Specter MH * 520. Example 33? / Í-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? íí, íV2-dimetilglicinamida The procedure described in Example 1 is repeated using y? / - methylglycine and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyI] -5- [2- (methylamino) ethoxy] quinazolin-4- amine (obtained as described in Example 1, preparation of starting materials) to give the title compound in 25% yield; NMR spectrum (DMSO-d6) 3.06 (s, 2H), 3.30 (s, 6H), 3.90 (t, 2H), 4.33-4.42 (m, 3H), 5.31 (s, 2H), 7.16 (d, 1H) , 7.24 (d, 1H), 7.34 (d, 1H), 7.35-7.40 (m, 1H), 7.53-7.57 (m, 1H), 7.60 (d, 1H), 7.70-7.75 (m, 1H), 7.86 -7.92 (m, 1H), 7.93 (d, 1H), 8.43 (s, 1H), 8.61 (d, 1H), 9.74 (s, 1H); Mass Spectrum MH * 507. Example 34? / -. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] etiI} -3-hydroxy -? /, 2,2-trimethylpropanamide The procedure described in Example 1 is repeated using 3-hydroxy-2,2-dimethylpropanoic acid and? / - [3-chloro-4- (pyridin-2-ylmeoxy) phenyl] -5- [2- (meitylamino) efoxy ] quinazolin-4-amine (obtained as described in the Example preparation of starting materials) to give the title compound in 25% yield; NMR spectrum (DMSO-d6) 1.07 (s, 6H), 3.15 (s, 3H), 3.35 (d, 2H), 3.91 (s, 2H), 4.41-4.48 (m, 3H), 5.30 (s, 2H) , 7.18 (d, 1H), 7.24 (d, 1H), 7.34 (d, 1H), 7.35-7.39 (m, 1H), 7.56-7.61 (m, 2H), 7.71-7.76 (m, 1H), 7.86 -7.91 (m, 1H), 7.98 (d, 1H), 8.45 (s, 1H), 8.60 (d, 1H), 9.81 (s, 1H); Mass Spectrum MH * 536. Example 35? I, -. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazoIin-5-yl) oxy] ethyl} -3-hydroxy-f-methylpropanamide (AZ12240261) The procedure described in Example 1 is repeated using 3-hydroxypropanoic acid and? / - [3-cyoro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (mephilamino) ethoxy] quinazolin-4-amine (obtained as described in Example 1, preparation of starting materials) to give the title compound in 24% yield; NMR spectrum (DMSO-d6) 2.13-2.26 (m, 2H), 2.65-2.79 (m, 2H), 3.30 (s, 3H), 3.87-3.97 (m, 2H), 4.1 3-4.25 (m, 1 H ), 4.34-4.61 (m, 2H), 5.31 (s, 2H), 7.1 5 (d, 1 H), 7.25 (d, 1 H), 7.32-7.39 (m, 2H), 7.53-7.57 (m, 1 H), 7.60 (d, 1 H), 7.70-7.76 (m, 1 H), 7.86-7.92 (m, 2H), 8.42 (s, 1 H), 8.61 (d, 1 H), 9.70 (s) , 1 HOUR); Mass Spec. MH * 508. Example 36 V-. { (2S) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide The procedure described in Example 1 is repeated using acetic acid and 5 - [(1 S) -2-amino-1-methyleneoxy] -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazoline -4-amine to give the title compound in 60% yield; NMR spectrum (DMSO-d6) 1.40 (d, 3H), 1.80 (s, 3H), 3.40 (m, 1H), 3.62 (m, 1H), 4.85 (m, 1H), 5.30 (s, 2H), 7.23 (m, 2H), 7.30 (d, 1H), 7.36 (m, 1H), 7.57 (m, 2H), 7.71 (t, 1H), 7.87 (td, 1H), 8.12 (d, 1H), 8.22 ( t, 1H), 8.49 (s, 1H), 8.58 (d, 1H), 10.00 (s, 1H); Mass Spectrum MH * 478. 5 - [(1 S) -2-am ino- 1 -meti-letoxy] -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine used as starting material is prepared as follows: The procedure described in Example 1 (preparation of initial maferials) is repeated using (S) - (+) - 1-amino-2-propanol and 5-fluoro-? / - [3 -chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine (obtained as described in Example 1, preparation of starting materials) to give 5 - [(1S) -2-amino- 1-methylethoxy] - / V- [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine in 46% yield; NMR spectrum (DMSO-d6) 1.39 (d, 3H), 2.96 (m, 2H), 4.79 (m, 1H), 5.28 (s, 2H), 7.17 (d, 1H), 7.21 (d, 1H), 7.29 (d, 1H), 7.35 (m, 1H), 7.56 (d, 1H), 7.64 (dd, 1H), 7.70 (t, 1H), 7.86 (di, 1H), 8.20 (d, 1H), 8.48 ( s, 1H), 8.58 (d, 1H), 10.60 (bs, 1H); Mass Spectrum MH * 435. Example 37 / -. { (2S) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxyacetamide The procedure described in Example 1 is repeated using glycolic acid and 5 - [(1 S) -2-amino-1-methylethoxy] -? / - [3-chloro-4- (pyridin-2-ylmethoxy ) phenyl] quinazolin-4-amine (obtained as described in Example 36, preparation of starting materials) to give the title compound in 47% yield; NMR spectrum (DMSO-d6) 1.20 (d, 3H), 3.41 (m, 1H), 3.74 (m, 1H), 3.78 (s, 2H), 4.92 (m, 1H), 5.29 (s, 2H), 5.48 (t, 1H), 7.23 (dd, 2H), 7.31 (d, 1H), 7.35 (m, 1H), 7.58 (m, 2H), 7.70 (i, 1H), 7.87 (td, 1H), 8.13 ( d, 1H), 8.17 (t, 1H), 8.47 (s, 1H), 8.58 (d, 1H), 9.98 (s, 1H); Specie of Mass MH * 494. Example 38 / Ví-. { (2S) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] etl} - 2, V2-dimethylglycinamide The procedure described in Example 1 is repeated using? /,? / - dimethylglycine and 5 - [(1S) -2-amino-1-methyleneoxy] -? / - [3-cioro-4- (pyridin-2 -ylmethoxy) phenyl] quinazolin-4-amine (obtained as described in Example 36, preparation of starting materials) to give the title compound in 49% yield; NMR spectrum (DMSO-d6) 1.38 (d, 3H), 2.07 (s, 6H), 2.80 (s, 2H), 3.41 (m, 1H), 3.73 (m, 1H), 4.93 (m, 1H), 5.29 (s, 2H), 7.23 (m, 2H), 7.30 (d, 1H), 7.35 (t, 1H), 7.58 (m, 2H), 7.70 (f, 1H), 7.86 (td, 1H), 8.12 ( m, 2H), 8.47 (s, 1H), 8.58 (d, 1H), 9.96 (s, 1H); Mass Spectrum MH * 521. Example 39 V-. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-methoxyacetamide The procedure described in Example 1 is repeated using methoxyacetic acid and 5 - [(1S) -2-amino-1-methylethoxy] -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin- 4-amine (obtained as described in Example 36, preparation of starting materials) to give the title compound in 53% yield; NMR spectrum (DMSO-d6) 1.39 (d, 3H), 3.20 (s, 3H), 3.40 (m, 1H), 3.72 1H), 3.75 (s, 2H), 4.93 (m, 1H), 5.29 (s, 2H), 7.23 (m, 2H), 7.31 (d, 1H), 7.58 (m, 2H), 7.70 (t, 1H), 7.86 (dt, 1H), 7.95 (s, 1H), 8.12 (d, 1H) ), 8.19 (1, 1H), 8.47 (s, 1H), 8.58 (m, 1H), 9.97 (s, 1H); Mass Spectrum MH * 508.

Example 40 / -. { (2S) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2- (methylsulfonyl) acetamide The procedure described in Example 1 is repeated using methanosulfonycidal acid and 5 - [(1 S) -2-amino-1-methylethoxy] -? / - [3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] quinazole N-4-amine (obtained as described in Example 36, preparation of starting materials) to give the title compound in 72% yield; NMR spectrum (DMSO-d6) 1 .42 (d, 3H), 3.02 (s, 3H), 3.49 (m, 1 H), 3.76 (m, 1 H), 4.06 (s, 2H), 4.89 (m, 1 H), 5.28 (s, 2H), 7.22 (m, 2H), 7.34 (m, 2H), 7.56 (d, 2H), 7.72 (t, 1 H), 7.86 (dt, 1 H), 8.15 ( d, 1 H), 8.48 (s, 1 H), 8.58 (d, 1 H), 8.71 (t, 1 H), 9.93 (s, 1 H); Mass Spectrum MH * 556. Example 41 V-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-Hydroxyacetamide The procedure described in Example 1 is repeated using glycolic acid and 5- (2- (aminoethoxy) -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine (obtained as described in Example 2.6, preparation of starting materials) to give the title compound in 60% yield: NMR spectrum (DMSO-d6) 3.71 (q, 2H), 3.78 (d, 2H), 4.36 (t , 2H), 5.28 (s, 2H), 5.49 (t, 1 H), 7.13 (d, 1 H), 7.21 (d, 1 H), 7.32 (d, 1 H), 7.35 (m, 1 H) , 7.56 (m, 2H), 7.71 (t, 1 H), 7.87 (dt, 1 H), 7.98 (d, 1 H), 8.1 8 (t, 1 H), 8.45 (s, 1 H), 8.58 (d, 1 H), 9.82 (s, 1 H); Mass Spectrum MH * 480. Example 42 Wí- { 2 - [(4- { [3-Chloro-4- (pyridin-2- ylmetoxy) phenyl] amino.}. quinazolin-5-yl) oxy] ethyl.} - - V2, / V2-dimethylglycinamide The procedure described in Example 1 is repeated using? /,? / - dimethylglycine and 5- (2- (amino-ethoxy) -? / - [3-chloro-4- (pyridin-2-methoxy) phenyl] quinozolin-4-amine (obtained as described in Example 2.6, preparation of starting materials) to give the title compound in 31% yield: NMR spectrum (DMSO-d6) 2.08 (s, 6H), 2.79 (s) , 2H), 3.68 (q, 2H), 4.36 (t, 2H), 5.29 (s, 2H), 7.13 (d, 1H), 7.21 (d, 1H), 7.34 (m, 2H), 7.55 (m, 2H), 7.70 (t, 1H), 7.86 (dt, 1H), 7.98 (d, 1H), 8.11 (t, 1H), 8.45 (s, 1H), 8.58 (d, 1H), 9.80 (s, 1H) ); Mass Spectrum MH * 507. Example 43 / V- {2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) pheny] amino} quinazolin- 5-yl) oxy] etiI.} -2-methoxyacetamide The procedure described in Example 1 is repeated using methoxyacetic acid and 5- (2-aminoethoxy) -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine (obtained as described in Example 2.6, preparation of starting materials) to give the title compound in 50% yield; NMR spectrum (DMSO-d6) 3.20 (s, 3H), 3.68 (m, 2H), 3.73 (s, 2H), 4.38 (t, 2H), 5.29 (s, 2H), 7.14 (d, 1H), 7.21 (d, 1H), 7.34 (m, 2H), 7.55 (f, 1H), 7.71 (i, 1H), 7.86 (f, 1H), 7.97 (d, 1H), 8.17 (m, 1H), 8.44 ( s, 1H), 8.58 (d, 1H), 9.81 (s, 1H); Mass Spectrum MH * 494.

Example 44? R-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazoIin-5-yl) oxy] ethyl} -2- (methylsulfonyl) acetamide The procedure described in Example 1 is repeated using methanesulfonylacetic acid and 5- (2-aminoethoxy) -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine (obtained as described in Example 2.6, preparation of starting materials) to give the title compound in 51% yield; NMR spectrum (DMSO-d6) 2.99 (s, 3H), 3.74 (m, 2H), 4.04 (s, 2H), 4.34 (t, 2H), 5.29 (s, 2H), 7.1 3 (d, 1 H) , 7.22 (d, 1 H), 7.35 (m, 2H), 7.55 (m, 2H), 7.71 (t, 1 H), 7.87 (dt, 1 H), 8.03 (d, 1 H), 8.46 (s) , 1 H), 8.58 (d, 1 H), 8.76 (t, 1 H), 9.79 (s, 1 H); Mass Spectrum MH * 542. Example 45? F-. { (2S) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} q uinazolin-5-yl) oxy] propyl} -? / - methylacetamide The procedure described in Example 1 is repeated using acetic acid and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5 - [(1 S) -1-methyl-2- (methylamino) ethoxy] quinazolin-4-amine (obtained as described for the antipode R in Example 2.3, preparation of initial materials, using (2S) -2-methylxiran) to give the title compound in 51% yield; NMR spectrum (DMSO-d6) 1 .36 (d, 3H), 1.94 (s, 3H), 3.03 (s, 3H), 3.32 obscured by H2O), 4.20 (m, 1 H), 5.08 (m, 1 H), 5.30 (s, 2H), 7.23 (m, 2H), 7.34 (m, 2H), 7.57 (d, 1 H), 7.68 (m, 2H), 7.87 (dt, 1 H), 8.1 1 (d, 1 H), 8.46 (s, 1 H), 859 (d.1 H). 9.94 (s.1 H); Mass Spectrum MH * 492. Example 46? / -. { (2S) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxy -? / - methylacetamide The procedure described in Example 1 is repeated using glycolic acid and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyI] -5 - [(1 S) -1-methyl-2- (methylamino) eioxy] quinazolin-4-amine (obfenide as described for the antipode R in Example 2.3, preparation of starting materials) to give the compound of the title in 53% yield; NMR spectrum (DMSO-d6) 1 .39 (d, 3H), 2.96 (s, 3H), 3.36 (dd, 1H), 4.04 (d, 2H), 4.21 (m, 1H), 4.37 (f, 1H) , 5.09 (m, 1H), 5.29 (s, 1H), 7.25 (m, 2H), 7.35 (m, 2H), 7.57 (d, 1H), 7.65 (dd, 1H), 7.70 (t, 1H), 7.87 (dt, 1H), 8.12 (d, 1H), 8.46 (s, 1H), 8.58 (d, 1H), 9.93 (s, 1H); Specimen of Mass MH * 508. Example 47 / Ví-. { (2S) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -_V, W2, / V2-trimethylglycinamide The procedure described in Example 1 is repeated with the use of? /, / V-dimethylyglycine and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5 - [(1S) -1-meityl-2 - (methylamino) ethoxy] quinazolin-4-amine (obfenide as described for antipode R in Example 2.3, preparation of initial materials) to give the title compound in 27% yield; NMR spectrum (DMSO-d6) 1.37 (d, 3H), 2.06 (s, 6H), 3.08 (s, 3H), 3.23 (dd, 1H), 3.25 (s, 2H), 4.26 (dd, 1H), 5.10 (m, 1H), 5.29 (s, 2H), 7.23 (m, 2H), 7.30 (d, 1H), 7.35 (m, 1H), 7.56 (s, 1H), 7.68 (m, 2H), 7.87 (m, dt, 1H), 8.13 (d, 1H), 8.44 (s, 1H), 8.58 (d, 1H), 9.90 (s, 1H); Mass Spectrum MH * 535. Example 48 _V-. { (2S) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-methoxy- / V-methylacetamide The procedure described in Example 1 is repeated using methoxyacetic acid and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5 - [(1S) -1 -methyl-2- (methylamino) ethoxy] quinazolin-4-amine (obtained as described for the amphipid R in Example 2.3, preparation of initial substances) to give the title compound in 39% yield; NMR spectrum (DMSO-d6) 1.38 (d, 3H), 2.99 (s, 3H), 3.16 (s, 3H), 3.27 obscured by 4.03 (s, 2H), 4.23 (m, 1H), 5.11 (m, 1H ), 5.29 (s, 2H), 7.24 (m, 2H), 7.30 (d, 1H), 7.35 (m, 1H), 7.57 (d, 1H), 7.65, (dd, 1H), 7.71 (t, 1H) ), 7.86 (dt, 1H), 8.12 (d, 1H), 8.44 (s, 1H), 8. 58 (d, 1H), 9.90 (s, 1H); Mass Spectrum MH * 522. Example 49? -. { (2S) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} - / V-methyl-2- (methylsulfonyl) acetamide The procedure described in Example 1 is repeated using methylene sulfonylacetic acid and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5 - [(1S) -1-methyl-2- (m ethyl ami) no) ethoxy] quinazolin-4-amine (obtained as described for antipode R in Example 2.3, preparation of starting materials) to give the title compound in 61% yield; NMR spectrum (DMSO-d6) 1.38 (d, 3H), 2.95 (s, 3H), 3.15 (s, 3H), 3.37 (d, 1H), 4.30 (m, 1H), 4.41 (d, 2H), 5.11 (m, 1H), 5.29 (s, 2, H), 7.24 (m, 2H), 7.30 (d, 1H), 7.35 (m, 1H), 7.57 (d, 1H), 7.64 (dd, 1H), 7.70 (t, 1H), 7.86 (dt, 1H), 8.11 (d, 1H), 8.45 (s, 1H), 8.58 (d, 1H), 9.88 (s, 1H); Mass Spectrum MH * 570. Example 50? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyrazin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? - methylacetamide The procedure described in Example 4.1 is repeated using? / - [(2R) -2- (. {4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl}. Oxy) propyl] -? / - methylacetamide and pyrazin-2-ylmethyl methanesulfonate to give the title compound in 61% yield; NMR spectrum (DMSO-d6) 1.3 (d, 3H), 1.95 (s, 3H), 3.03 (s, 3H), 3.37 (1H obscured by H2O), 4.21 (dd, 1H), 5.08 (m, 1H), 5.37 (s, 2H), 7.29 (m, 3H), 7.70 (m, 2H), 8.11 (d, 1H), 8.46 (s, 1H), 8.66 (m, 2H), 8.85 (s, 1H), 9.94 (s, 1H); Mass Spec. MH * 493.? / - [(2R) -2- ( { 4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.} Oxy) propyl] -? -methylated acetic acid as initial material is prepared as follows: The procedure described in Example 3 (preparation of starting materials) is repeated using acetic acid and 2-chloro-4- (. {5 - [(1R) -1-methyl) -2- (methylamino) ethoxy] quinazolin-4-amino) phenol (obtained as described in Example 4.11, preparation of starting materials) to give? / - [(2R) -2- (. {4 - [( 3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.} Oxy) propyl] - / V-methylacetamide in 45% yield; NMR spectrum (DMSO-d6) 1.37 (d, 3H), 1.94 (s, 3H), 3.03 (s, 3H), 3.31 (d, 1H), 4.15 (dd, 1H), 5.06 (m, 1H), 6.97 (d, 1H), 7.23 (d, 1H), 7.29 (d, 1H), 7.46 (dd, 1H), 7.69 (m, 1H), 7.95 (d, 1H), 8.42 (s, 1H), 9.98 ( bs. 1H); Mass Spectrum MH * 401. Example 51 N-. { (2R) -2 - [(4- {[3-chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} - / V-methylacetamide The procedure described in Example 3 is repeated using? / - [(2R) -2- (. {4 - [(3-chloro-4-h idroxyphenyl) amino] qu mal-5-yl. oxi) propyl] -? / - methylacetamide (obtained as described in Example 50, preparation of starting materials) and 4- (chloromethyl) -thiazole hydrochloride to give the title compound in 17% yield; NMR spectrum (DMSO-d6) 1 .36 (d, 3H), 1.94 (s, 3H), 3.02 (s, 3H), 3.30 obscured by H2O), 4.21 (dd, 1 H), 5.09 (m, 1 H), 5.33 (s, 2H), 7.29 (m, 3H), 7.70 (m, 2H), 7.81 (s, 1 H), 8.08 (s, 1 H), 8.47 (s, 1 H), 9.1 3 (s, 1 H), 9.96 (s, 1 H); Mass Spectrum MH * 498. Example 52? - ((2R) -2-. {(4- (. {3-Chloro-4 - [(2-fluorobenzyl) oxy] phenyl} amino) quinazoline -5-yl] oxy}. Propyl) -? / - methylacetamide The procedure described in Example 3 is repeated using? / - [(2R) -2- (. {4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl}. Oxy) propyl] -? / - methylacetamide (obtained as described in Example 50, preparation of starting materials) and 3-fluorobenzyl chloride to give the title compound in 87% yield; NMR spectrum (DMSO-d6) 1 .36 (d, 3H), 1.93 (s, 3H), 3.04 (s, 3H), 3.27 (1 H obscured by H2O), 4.22 (dd, 1 H), 5.07 (m, 1 H), 5.25 (s, 2H), 7.16 (1, 1H), 7.29 (m, 5H), 7.45 (m, 1H), 7.65 (dd, 1H), 7.71 (í, 1H), 8.09 (d, 1H), 8.46 (s, 1H), 9.93 (s, 1H); Mass Spectrum MH * 509. Example 53 W - (? 2R) -2-. { [4- (. {3-Chloro-4 - [(2-fluorobenzyl) oxy] phenyl} amino) quinazolin-5-yl] oxy} propyl) - / V-methylacetamide The procedure described in Example 3 is repeated using? / - [(2R) -2- ( { 4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.} Oxy) propyl] -? / - methylacetamide (obtained as described in Example 50, preparation of starting materials) and 2-fluorobenzyl chloride to give the title compound in 72% yield; NMR spectrum (DMSO-d6) 1.37 (d, 3H), 1.94 (s, 3H), 3.04 (s, 3H), 3.30 (1H obscured by H2O), 4.20 (dd, 1H), 5.07 (m, 1H), 5.25 (s, 2H), 7.27 (m, 5H), 7.43 (m, 1H), 7.59 (t, 1H), 7.67 (d, 1H), 7.70 (t, 1H), 8.07 (d, 1H), 8.45 (s, 1H), 9.93 (s, 1H); Mass Spectrum MH * 509. Example 54? V-. { (1R) -2 - [(4- {[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} -2-hydroxy -? / - methylacetamide The procedure described in Example 3 is repeated using picolyl chloride hydrochloride and? / - [(1) -2- (. {4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.} oxi) -1-methylethyl] -2-hydroxy -? / - meitylacetamide to give the title compound in 8% yield; NMR spectrum (DMSO-d6) 1 .19 (d, 3H), 2.79 (s, 3H), 3.87-4.26 (m, 3H), 4.38-4.48 (m, 2H), 5.1 1 -5.22 (m, 1 H ), 5.29 (s, 2H), 7.18-7.25 (m, 2H), 7.32-7.38 (m, 2H), 7.48 (d, 1 H), 7.58 (d, 1 H), 7.72 (t, 1 H) , 7.87 (t, 1 H), 7.94 (d, 1 H), 8.44 (s, 1 H), 8.59 (d, 1 H), 9.58 (s, 1 H); Mass Spectrum MH * 508.3. ? / - [(1 R) -2- ( { 4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.} Oxy) -1-methyl-ethyl] -2-hydroxy-? / -methylacetamide used as starting material is prepared as follows: The procedure described in Example 3 (preparation of initial materials) is repeated using (2R) -2- (methylamino) propan-1-ol (obtained as described in Becker et al. al, J. Chem. Soc. 1957,858) and 2-chloro-4 - [(5-fluoroquinazolin-4-yl) amino] phenol (obtained as described in Example 4.5, preparation of starting materials) to give 2 -chloro-4 - [(5- { [(2R) -2- (methylamino) propyl] oxy} quinazolin-4-yl) amino] phenol in > 100% production; Specimen NMR (DMSO-d6) 1.20 (d, 3H), 2.40 (s, 3H), 3.30 (m, 1H), 4.25 (d, 1H), 4.35 (dd, 1H), 7.00 (d, 1H), 7.10 (d, 1H), 7.30 (d, 1H), 7.60 (dd, 1H), 7.70 (f, 1H), 7.90 (d, 1H), 8.50 (s, 1H); Mass Spectrum MH * 359.1 The procedure described in Example 3 (preparation of starting materials) is repeated using glycolic acid and 2-chloro-4 - [(5 { [(2R) -2- (methylamino) propyl] oxy}. quinazolin-4-yl) amino] phenol to give N - [(1R) -2- (. {4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl}. oxy) -1-methylethyl] -2-hydroxy -? / - methylacetamide in 100% yield; Mass Spectrum MH * 416.9 Example 55? F-. { (1R) -2- [. { 4-. { [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy-1-methylethyl} - / V-methylacetamide The procedure described in Example 3 is repeated using picolyl chloride hydrochloride and? / - [(1R) -2 (. {4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl}. oxy) -1-methylethyl] -? / - methylacetamide to give the title compound in 7% yield; NMR spectrum (DMSO-d6) 1.18 (d, 3H), 1.83 (s, 3H), 2.84 (s 3H), 4.19-4.43 (m, 2H), 5.14-5.24 (m, 1H), 5.30 (s, 2H) ), 7.16-7.27 (m, 2H), 7.32-7.38 (m, 2H), 7.45-7.50 (m, 1 H), 7.58 (d, 1 H), 7.72 (t, 1 H), 7.87 (t, 2H), 8.43 (s, 1 H), 8.59 (d, 1 H), 9.53 (s, 1 H); Mass Spectrum MH * 492.3. / V - [(1 R) -2- ( { 4 - [(3-Chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.}. Oxy) -1-methyl ethyl] - / / V-methylacetamide used as the starting material is prepared as follows: The procedure described in Example 3 (preparation of starting materials) is repeated using acetic acid and 2-chloro-4 - [(5 { [(2R) -2- (methylamino) propyl] oxy}. quinazolin-4-yl) amino] phenol (obtained as described in Example 54, preparation of starting materials) to give? / - [(1 R) -2- (. {4- [ (3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.} Oxy) -1-methylethyl] -? / - mefilacef amide in 100% yield; Mass Spectrum MH * 401. Example 56? / -. { (1 S) -2 - [(4- {[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyethyl} -2-hydroxy -? / - methylacetamide The procedure described in Example 3 is repelled using picolyl chloride hydrochloride and? / - [(1 S) -2- (. {4 - [(3-chloro-4-hydroxy-phenyl) amine] quinazolin-5- il.}. oxy) -1 -mephylethyl] -2-hydroxy-? / - meitylaceaeamide to give the title compound in 57% yield; NMR spectrum (DMSO-d6) 1 .20 (dd, 3H), 2.80 (d, 3H), 3.10 (m, 1 H), 3.80-4.20 (m, 2H), 4.20-4.50 (m, 2H), 5.15 (m, 1H), 5.30 (s, 2H), 7.20 (m, 2H), 7.30 (m, 2H), 7.50 (d, 1H), 7.60 (d, 1H), 7.70 (m, 1H), 7.80- 7.95 (m, 2H), 8.40 (d, 1H), 8.60 (d, 1H), 9.60 (s, 1H); Mass Spectrum MH * 508.2. ? H (1 S) -2- ( { 4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.}. Oxy) -1-methylethyl] -2-hydroxy -? / - methylacetamide used as the starting material is prepared as follows: The procedure described in Example 3 (preparation of starting materials) is repeated using (2S) -2- (methylamino) propan-1-ol (obtained as described in Chacchio et al., Tetrahedron , 1995, 51, 5689) and 2-chloro-4 - [(5-fluoroquinazolin-4-yl) amino] phenol (obtained as described in Example 4.5, preparation of starting materials) to give 2-chloro-4- [(5-. {[[(2S) -2- (methylamino) propyl] oxy} quinazolin-4-yl) amino] phenol in > 100% production; NMR spectrum (DMSO-d6) 1.20 (d, 3H), 2.40 (s, 3H), 3.20 (m, 1H), 4.15 (dd, 1H), 4.30 (dd, 1H), 7.00 (d, 1H), 7.10 (d, 1H), 7.30 (d, 1H), 7.60 (dd, 1H), 7.70 (t, 1H), 8.00 (d, 1H), 8.50 (s, 1H); Mass Spectrum MH * 359.4. The procedure described in Example 3 (preparation of starting materials) is repeated using glycolic acid and 2-chloro-4 - [(5 { [(2S) -2- (methylamino) propyl] oxy} quinazolin- 4-yl) amino] phenol to give N - [(1S) -2- (. {4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl}. Oxy) -1-methylethyl ] -2-hydroxy -? / - mefilacetamide in 48% yield; Mass Spectrum: MH * 417.3. Example 57 V-. { (1S) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methylethyl} -? / - metilacetamïda The procedure described in Example 3 is repeated using pycolyl chloride hydrochloride and? / - [(1S) -2- (. {4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.} . oxy) -1-methylethyl] -? / - methylacetylamide to give the title compound in 34% yield; NMR spectrum (DMSO-d6, 373K) 1.20 (d, 3H), 1.85 (s, 3H), 2.80 (s, 3H), 3.00 (m, 1H), 4.30 (m, 1H), 4.40 (m, 1H) , 5.30 (s, 2H), 7.20 (m, 2H), 7.40 (m, 2H), 7.50 (d, 1H), 7.60 (d, 1H), 7.70 (1, 1H), 7.80 (m, 1H), 7.90 (d, 1H), 8.40 (s, 1H), 8.60 (el, 1H), 9.60 (s, 1H); Mass Spectrum MH * 492.2. ? / - [(1S) -2- ( { 4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.} Oxy) -1-methylethyl] -? / - methylacetamide used as the starting material is prepared as follows: The procedure described in Example 3 (preparation of starting materials) is repeated using acetic acid and 2-chloro-4 - [(5 { [(2S) -2- (mephilamino) propyl] oxy}. quinazolin-4-yl) amino] phenol (obtained as described in Example 56, preparation of starting materials) to give? / - [(1S) -2- (. {4 - [( 3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.} Oxy) -1-methylethyl] -? / - methylacetamide in 27% yield; Mass Spectrum MH * 401 .3. Example 58 jV-. { (1 S) -2 - [(4. {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methylethi} -2-methoxy- / V-methylacetamide The procedure described in Example 3 is repeated using picolyl chloride hydrochloride and? / - [(S) -2- (. {4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl) .}. oxi) -1-methylethyl] -2-meioxy-β-methylacetamide to give the compound of the title in 39% yield; NMR spectrum (DMSO-d6, 373K) 1 .20 (m, 3H), 2.80 (s, 3H), 3.10 (s, 3H), 3.90 (m, 2H), 4.20 (m, 1 H), 4.50 (m , 1 H), 5.1 0 (m, 1 H), 5.30 (s, 2H), 7.20 (m, 2H), 7.40 (m, 2H), 7.50 (d, 1 H), 7.60 (d, 1 H) , 7.70 (t, 1 H), 7.90 (f, 1 H), 7.95 (s, 1 H), 8.40 (s, 1 H), 8.60 (d, 1 H), 9.60 (s, 1 H); Mass Spectrum MH * 522.2. ? / - [(1 S) -2- ( { 4 - [(3-chloro-4-hydroxy-phenyl) amino] quinazolin-5-yl}. Oxy) -1-methylethyl] -2-methoxy-? / -methylaceaeamide used as starting material is obtained as follows: The procedure described in Example 3 (preparation of starting materials) is repeated using acyclic meioxy acid and 2-chloro-4 - [(5- { [(2S) -2 - ((methylamino) propyl] oxy}. quinazolin-4-yl) amino) phenol (obtained as described in Example 56, preparation of starting materials) to give? / - [(1 S) -2- (. { 4 - [(3-chloro-4-hydroxy-phenyl) amino] quinazolin-5-yl}. Oxy) -1-methylethyl] -2-methoxy-N-methylacetamide in 49% yield; Specter of Mass MH * 429.2. Example 59 / V-. { (1 S) -2 - [(4- {[C-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quininazol? N-5-yl) oxy] -1-methyl ethyl} -2-hydroxyacetamide The procedure described in Example 3 is repeated using picolyl chloride hydrochloride and? / - [(1 S) -2- (. {4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl} oxy) -1-methylphylloxy] -2-hydroxyacemamide to yield the compound of the 57% yield; Specimen NMR (DMSO-d6) 1 .23 (d, 3H), 3.64-3.81 (m, 2H), 4.24-4.36 (m, 2H), 4.45-4.59 (m, 1 H), 5.29 (s, 2H) , 5.45 (t, 1 H), 7.1 3-7.23 (m, 2H), 7.35 (t, 2H), 7.49-7.53 (m, 1 H), 7.56-7.59 (m, 1 H), 7.72 (t, 1 H), 7.87 (t, 1 H), 7.99-8.02 (m, 2H), 8.46 (s, 1 H), 8.59 (d, 1 H), 9.75 (s, 1 H); Specter of Mass MH * 493.95. ? / - [(1 S) -2- ( { 4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.}. Oxy) -1-methylethyl] -2-hydroxyacetamide used as Initial material is prepared as follows: The procedure described in Example 3 (preparation of starting materials) is repeated using (2S) -2-aminopropan-1 -ol and 2-chloro4 - [(5-fluoroquinazolin-4-yl) amino ] phenol (obtained as described in Example 4.5, preparation of starting materials) to give 4 - [(5- {[[(2S) -2-aminopropyl] oxy} quinazolin-4-yl) amino] -2- chlorophenol in 54% yield; NMR spectrum (DMSO-d6); 1.30 (d, 3H), 3.30 (bs, 2H), 3.80 (m, 1 H), 4.40 (m, 2H), 7.00 (d, 1 H), 7.20 (d, 1 H), 7.30 (d , IH), 7.50 (dd, 1 H), 7.70 (t, 1 H), 8.00 (d, 1 H), 8.45 (s, 1 H); Mass Spectrum MH * 345.1. The procedure described in Example 3 (preparation of starting materials) is repeated using glycolic acid and 4- (5- { [(2S) -2-aminoprop-1] oxy} quinazolin-4-yl) amino] -2-chlorophenol to give? / - [(1 S) -2- ( { 4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.} Oxy) -1 -methylethyl] -2-hydroxyacetamide in 73% yield; Mass Spectrum MH * 403.0. Example 60? / -. { (1 S) -2 - [(4- {[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} acetamide The procedure described in Example 3 is repeated using picolyl chloride hydrochloride and? / - [(1 S) -2- (. {4- (3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.} oxi) -1-methylphiolide] aceyamide to give the title compound in 63% yield; NMR spectrum (DMSO-d6), 1.21 (s, 3H), 1.73 (s, 3H), 4.12-4.30 (m, 2H), 4.33-4.43 (m, 1 H), 5.29 (s, 2H) ), 7.15-7.25 (m, 2H), 7.35 (t, 2H), 7.51 -7.59 (m, 2H), 7.72 (t, 1 H), 7.87 (l, 1 H), 7.99 (s, 1 H) , 8.14 (d, 1 H), 8.48 (s, 1 H), 8.59 (d, 1 H), 9.80 (s, 1 H); Mass Spectrum MH * 478.0. ? / - [(1 S) -2- ( { 4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.}. Oxy) -1-methylethyl] acetamide used as starting material prepare as follows: The procedure described in Example 3 (preparation of starting materials) is repeated using acetic acid and 4- (5- ({(2S) -2-aminopropyl] oxy} quinazolin-4-yl) amino ] -2-chlorophenol (obtained as described in Example 59, preparation of starting materials) to give? / - [(1 S) -2- (. {4 - [(3-chloro-4-hydroxyphenyl) amine] ] quinazolin-5-yl.}. oxy) -1-methylethyl] acetamide in > 100% production; Mass Spec. MH * 387.0 Example 61 N1-. { (1 S) -2 - [(4 . { [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methylethyl} -? 2, iV2-dimethylglycinamide The procedure described in Example 1 is repeated using? /. ? / - d, methylglycine and 5-. { [(2S) -2-aminopropyl] oxy} -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine to give the title compound in 42% yield; NMR spectrum (DMSO-d6) 1 .21 (d, 3H), 2.05 (s, 6H), 2.60-2.80 (m, 2H), 4.20-4.40 (m, 2H), 4.40-4.60 (m, 1 H) , 5.30 (s, 2H), 7.15 (m, 1 H), 7.22 (m, 1 H), 7.35 (m, 2H), 7.54 (m, 2H), 7.70 (t, 1 H), 7.90 (t, 1 H), 7.98 (m, 2H), 8.48 (s, 1 H), 8.59 (d, 1 H), 9.76 (s 1 H): Mass Spectrum MH * 521 .4. 5-. { [(2S) -2-aminopropyl] oxy} -N- [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine used as starting material is prepared as follows: The procedure described in Example 2.4 (preparation of starting materials) is repeated using (2S) -2-aminopropan-1 -ol and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5-fluoroquinazolin-4-amine (obtained as described in Example 1, preparation of initial materials) to give 5-. { [(2S) -2-aminopropyl] oxy} -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine in 51% yield; Mass Spectrum M H * 436.4. Example 62 andV1-. { (2R) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} - / V2, V2-dimethylglycinamide The procedure described in Example 3 is repeated using / V1 - [(2R) -2- (. {4 - [(3-chloro-4-hydroxyphenyl) amino] quinazoln-5-yl] oxy) propyl] -? / 2, / V2-dimethylglycinamide and picolyl chloride hydrochloride to give the title compound in 59% yield; NMR spectrum (CDCI3) 1.47 (d, 3H), 2.11 (s, 6H), 2.88 (s, 2H), 3.50-3.63 (m, 1H), 3.64-3.78 (m, 1H), 4.76-4.90 (m, 1H), 5.23 (s, 2H), 6.92-7.00 (m, 2H), 7.13-7.19 (m, 1H), 7.36-7.49 (m, 2H), 7.52-7.72 (m, 4H), 7.90 (d, 1H), 8.55 (m, 2H), 9.82 (s, 1H); Mass Spectrum MH * 521.0. ? / 1 - [(2R) -2- ( { 4 - [(3-chloro-4-hydroxyphenyl) amino] quinazoIin-5-yl.} Oxy) propyl] -? / 2,? / 2- dimethylglycinamide amide used as starting material is prepared as follows: The procedure described in Example 3 (preparation of starting materials) is repeated using 4- (. {5 - [(1R) -2-amino-1-methylehoxy] quinazoline4- il.} amino) -2-chlorophenol (obtained as described in Example 4.4, preparation of starting materials) and? /,? / - dimethylglycine to give? / 1 - [(2R) -2- ( { 4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl}. Oxy) propyl] -? / 2,? / 2-dimethylglycinamide amide in 11% yield; NMR spectrum (CDC) 1.46 (d, 3H), 2.09 (s, 6H), 2.84 (d, 2H), 3.52-3.75 (m, 2H), 4.77-4.89 (m, 1H), 6.89-6.99 (m, 2H), 7.27 (dd, 1H), 7.40 (dd, 1H), 7.51-7.61 (m, 2H), 7.80 (d, 1H), 8.52 (s, 1H), 9.76 (s, 1H); Mass Spectrum MH * 430.0. Example 63 (2S) -V-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2,4-dihydroxybutanamide 9? , o ^ j ^ Dr 5- (2-Amino-eneoxy) -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine (obtained as described in Example 2.6, preparation of initial materials, 0.5 g, 1.19 mmol) is heated at 130 ° C in xylene (20 ml) until it has dissolved. (S) - (-) - α-hydroxy-β-butyrolactone (0.10 ml, 1.31 mmol) is added and the mixture is stirred at 1 30 ° C for 3 hours. More (S) - (-) - a-hydroxy -? - butyrolactone (0.05 ml, 0.66 mmol) is added and the mixture is heated for 2 more hours. The resulting precipitate is filtered while the mixture was hot, rinsed with diethyl ether (3 x 10 ml) and dried to give the title compound as a solid (430 mg, 69%); NMR spectrum (DMSO-d6) 1 .38-1 .55 (m, 1 H), 1 .69-1 .85 (m, 1 H), 3.37-3.50 (m, 2H), 3.61 -3.77 (m, 21 1), 3.89-4.00 (m, 1 H), 4.28-4.45 (m, 3H), 5.29 (s, 2H), 5.51 (d, 1 H), 7.13 (d, 1 H), 7.22 (d, 1 H), 7.28-7.41 (m, 2H), 7.49-7.62 (m, 2H), 7.71 (t, 1 H), 8.01 (d, 1 H), 8.14-8.25 (m, 1 H), 8.45 ( s, 1 H), 8.59 (d, 1 H), 9.82 (s, 1 H); Mass Spectrum MH * 523.9 Example 64 (2R) - / -. { 2 - [(4. {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazoIin-5-yl) oxy] ethyl} -2,4-dihydroxybutanamide The procedure described in Example 63 is repeated by using 5- (2-aminoethoxy) -N- [3-chloro-4- (pyridin-2-ylmethoxy) pheny1] quinazolin-4-amine (obfenide as described in Example 2.6, preparation of starting materials) and (R) - (+) - a-hydroxy-γ-butyrolactone to give the title compound in 55% yield; NMR spectrum (DMSO-d6) 1.38-1.55 (m, 1H), 1.69-1.85 (m, 1H), 3.37-3.50 (m, 2H), 3.61-3.77 (m, 2H), 3.89-4.00 (m, 1H) ), 4.28-4.45 (m, 3H), 5.29 (s, 2H), 5.51 (d, 1H), 7.13 (d, 1H), 7.22 (d, 1H), 7.28-7.41 (m, 2H), 7.49- 7.62 (m, 2H), 7.71 (t, 1H), 8.01 (d, 1H), 8.14-8.25 (m, 1H), 8.45 (s, 1H), 8.59 (d, 1H), 9.82 (s, 1H); Mass Spectrum MH * 523.9. Example 65 (2R) -? R-. { (2R) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4-dihyd roxy butanam gone The procedure described in Example 63 is repeated using 5 - [(1) -2-amino-1-methylethoxy] -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine and (R) - (+) - a-hydroxy-γ-butyrolactone to give the title compound in 54% yield; NMR spectrum (DMSO-d6) 1.39 (d, 3H), 1.43-1.57 (m, 3H), 1.71-1.86 (m, 1H), 3.33-3.53 (m, 3H), 3.65-3.79 (m, 1H), 3.88-4.00 (m, 1H), 4.36 (t, 1H), 4.85-4.96 (m, 1H), 5.29 (s, 2H), 5.45 (d, 1H), 7.24 (d, 2H), 7.28-7.41 ( m, 2H), 7.59 (t, 2H), 7.71 (t, 1H), 7.87 (t, 1H), 8.10-8.21 (m, 2H), 8.48 (s, 1H), 8.59 (d, 1H), 9.99 (s, 1H); Mass Spectrum MH * 537.9. 5 - [(1R) -2-amino-1-methyleneoxy] -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine used as starting material is prepared as follows: Benzaldehyde (1.46 ml, 14.3 mmol) is added to a solution of 4- (. {5 - [(1R) -2-amino-1-methylethoxy] quinazolin-4-yl}. Amino) -2-chlorophenol (obtained as described in Example 4.4, preparation of starting materials, 4.5 g, 13.08 mmol) in DMF (50 ml) and the mixture is stirred for 20 min. Potassium carbonate (7.23 g, 52.32 mmol), picolyl chloride hydrochloride (2.57 g, 15.70 mmol) and 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6 / catalytic amount) are added and the The reaction mixture is stirred vigorously for 16 hours. The reaction mixture is concentrated, the residue is stirred in water (250 ml) and the precipitated solid is filtered. The solid is dissolved in 1M HCl (150 ml) and the solution is rinsed with ethyl acetate (3 x 50 ml). The aqueous phase is basified with 2M NaOH and the resulting precipitate is filtered to give 5 - [(1R) -2-amino-1-methyleneoxy] -? / - [3-chloro-4- (pyridin-2-ylmehoxy) phenyl ] quinazolin-4-amino (5.69 g, 100%); NMR spectrum (DMSO-d6) 1.39 (d, 3H), 2.88-3.05 (m, 2H), 4.74-4.86 (m, 1H), 5.28 (s, 2H), 7.14-7.25 (m, 2H), 7.30 ( d, 1H), 7.33-7.40 (m, 1H), 7.57 (d, 1H), 7.65 (dd, 1H), 7.70 (dt, 1H), 7.87 (dt, 1H), 8.20 (d, 1H), 8.49 (s, 1H), 8.56-8.61 (m, 1H). Example 66 (2S) -? F-. { (2R) -2 - [(4- {[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4-dihydroxybutanamide The procedure described in Example 63 is repeated using 5 - [(1R) -2-amino-1-meilylefoxy) -? / - [3-chloro-4- (pyridin-2-ylmeloxy) phenyl] quinazolin-4-amine ( obtained as described in Example 65, preparation of initial maferials) and (S) - (-) - α-hydroxy-γ-butyrolactone to give the title compound in 78% yield; NMR spectrum (DMSO-d6) 1.31-1.47 (m, 4H), 1.64-1.77 (m, 1H), 3.33-3.50 (m, 3H), 3.71-3.84 (m, 1H), 3.90-4.00 (m 1H) , 4.32 (1.1H), 4.87-4.98 (, 1H), 5.29 (s, 2H), 5.48 (d, 1H), 7.18-7.27 (m, 2H), 7.28-7.40 (m, 2H), 7.54- 7.64 (m, 2H), 7.87 (di, 1H), 8.10-8.21 (m, 2H), 8.47 (s, 1H), 8.59 (d, 1H), 9.95 (s, 1H); Specter of Mass MH * 537.9. Example 67 (2R) -W-. { (2S) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4-dihydroxybutanamide The procedure described in Example 63 is repeated using 5 - [(1S) -2-amino-1-methylethoxy] -? / - [3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] quinazolin-4 -amine (obfenida as described in Example 36, preparation of initial materials) and (R) - (+) - a-hidroxi -? - buiroirolaííona to give the compound of the title in 62% production; NMR spectrum (DMSO-d6) 1.31-1.47 (m, 4H), 1.64-1.77 (m, 1H), 3.33-3.50 (m, 3H), 3.71-3.84 (m, 1H), 3.90-4.00 (m, 1H) ), 4.32 (t, 1H), 4.87-4.98 (m, 1H), 5.29 (s, 2H), 5.48 (d, 1H), 7.18-7.27 (m, 2H), 7.28-7.40 (m, 2H), 7.54-7.64 (m, 2H), 7.87 (dt, 1H), 8.10-8.21 (m, 2H), 8.47 (s, 1H), 8.59 (d, 1H), 9.95 (s, 1H); Mass Spectrum MH * 537.9. Example 68 (2S) -? F-. { (2S) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4-dihydroxybutanamide The procedure described in Example 63 is repeated using 5 - [(1S) -2-amino-1-methylethoxy] -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine (obtained as described in Example 36, preparation of initial materials) and (S) - (-) - α-hydroxy-β-bufirolacfone to give the title compound in 60% yield; NMR spectrum (DMSO-d6) 1.39 (d, 3H), 1.43-1.57 (m, 3H), 1.71-1.86 (m, 1H), 3.33-3.53 (m, 3H), 3.65-3.79 (m, 1H), 3.88-4.00 (m, 1H), 4.36 (t, 1H), 4.85-4.96 (m, 1H), 5.29 (s, 2H), 5.45 (d, 1H), 7.24 (d, 2H), 7.28-7.41 ( m, 2H), 7.59 (t, 2H), 7.71 (t, 1H), 7.87 (t, 1H), 8.10-8.21 (m, 2H), 8.48 (s, 1H), 8.59 (d, 1H), 9.99 (s, 1H); Mass Spectrum MH * 537.9.

Example 69 (2S) - / V-. { (1R) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methylethyl} -2,4-dihydroxybutanamide The procedure described in Example 63 is repeated using 5-. { [(2R) -2-aminopropyl] oxy} -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine (obtained as described in Example 2.4, preparation of initial materials) and (S) - (-) - a-hydroxy-α-bufirolacíona to give the compound of the 79% production; NMR spectrum (DMSO-d6 400: MHz) 1.24 (d, 3H), 1.30-1.41 (m, 1H), 1.63-1.74 (m, 1H), 3.32-3.46 (m, 2H), 3.91-3.98 (m, 1H), 4.24 (dd, 1H), 4.31 (t, 1H), 4.38 (t, 1H), 4.47-4.57 (m, 1H), 5.30 (s, 2H), 5.43 (d, 1H), 7.16 (d, 1H), 7.23 (d, 1H), 7.31-7.41 (m, 2H), 7.56 (dd, 1H), 7.60 (d, 1H), 7.73 (t, 1H), 7.89 (dt, 1H), 7.95 (d, 1H), 8.06 (d, 1H), 8.48 (s, 1H), 8.61 (d, 1H) 9.79 (s, 1H); Mass Spectrum MH * 538.0. Example 70 (2R) -N-. { (1R) -2 - [(4- {[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methylethyl} -2,4-dihydroxybutanamide The procedure described in Example 63 is repeated using 5-. { [(2R) -2-aminopropyl] oxy} - / V- [3-Chloro-4- (pyridin-2-lmetoxy) phenyl] quinazolin-4-amine (obtained as described in Example 2.4, preparation of initial materials) and (R) - (+ ) -a-hydroxy-α-buyirolacíona to give the title compound in 77% yield; NMR spectrum (DMSO-d6) 1.22 (d, 3H), 1.46-1.60 (m, 1H), 1.72-1.86 (m, 1H), 3.38-3.51 (m, 2H), 3.83-3.93 (m, 1H), 4.20-4.40 (m, 3H), 4.42-4.55 (m, 1H), 5.29 (s, 2H), 5.39 (d, 1H), 7.14 (d, 1H), 7.21 (d, 1H), 7.30-7.40 ( m, 2H), 7.47-7.55 (m, 1H), 7.58 (d, 1H), 7.72 (t, 1H), 7.87 (t, 1H), 7.97 (d, 1H), 8.01 (s, 1H), 8.46 (s, 1H), 8.59 (d, 1H), 9.74 (s 1H): Mass Spectrum MH * 538.0 Example 71 (2R) - / V-. { 2 - [(4- {[3-Chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2, 4. di hydroxy butan ami da The procedure described in Example 63 is repeated by using 5- (2-aminoethoxy) -? / - [3-chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] quinazolin-4-amine and (R) - (+) - a-hydroxy-γ-butyrolactone to yield the title compound in 69% yield; NMR spectrum (DMSO-d6 400MHz) 1.44-1.55 (m, 1H), 1.73-1.85 (m, 1H), 3.41-3.52 (m, 2H), 3.65-3.77 (m, 2H), 3.93-4.02 (m, 1H), 4.31-4.48 (m, 3H), 5.38 (s, 2H), 5.50 (d, 1H), 7.17 (d, 1H), 7.33 (t, 2H), (7.60 (dd, 1H), 7.74 ( t, 1H), 7.83 (s, 1H), 8.02 (s, 1H), 8.20 (t, 1H), 8.48 (s, 1H), 9.17 (s, 1H), 9.85 (s, 1H); MH * 529.9 5- (2-aminoethoxy) -? / - [3-chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] quinazolin-4-amine used as starting material is prepared as follows: The procedure described in Example 3 (preparation of starting materials) is repeated using 2-chloro-4 - [(5-fIuoroquinazolin-4-yl) amino] phenol (obtained as described in Example 4.5, preparation of starting materials) and ethanolamine to give 4- {[[5- (2-aminoethoxy) quinazolin-4-yl] amino] -2-chlorophenol in 84% yield: NMR spectrum (DMSO-d6) 3.12 (t, 2H), 4.27 (t, 2H), 6.96 (d, 1H), 7.11 (d, 1H), 7.31 (d, 1H), 7.53 (dd, 1H), 8.08 (d, 1H), 8.47 (s, 1H); Mass MH * 331.0 The procedure described in Example 65 (preparation of starting materials) is repeated using 4-. { [5- (2-aminoethoxy) quinazolin-4-yl] amino} -2-chlorophenol and 4- (chloromethyl) -1,3-thiazole hydrochloride to give 5- (2-aminoethoxy) -? / - [3-chloro-4- (1,3-thiazole-4-ylmethoxy) phenyl ] quinazolin-4-amine in 91% production; NMR spectrum (DMSO-d6400MHz) 3.02-3.19 (bs, 2H), 4.22-4.36 (m, 2H), 5.33 (s, 2R), 7.14 (d, 1H), 7.27-7.40 (m, 2H), 7.67- 7.86 (m, 3H), 8.23 (s, 1H), 8.52 (s, 1H), 9.15 (s, 1H) (3 interchangeable); Mass Spectrum MH * 427.9. Example 72 (2S) - / V-. { 2 - [(4- {[3-Chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2,4-dihydroxybutanamide The procedure described in Example 63 is repeated by using 5- (2-aminoethoxy) -? / - [3-chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] quinazolin-4-amine (obtained as described in Example 71, preparation of starting materials) and (S) - (-) - a-hydroxy-γ-butyrolactone to give the title compound in 66% yield; NMR spectrum (DMSO-d6400MHz) 1.44-1.55 (m, 1H), 1.73-1.85 (m, 1 H), 3.41-3.52 (m, 2H), 3.65-3.77 (m, 2H), 3.93-4.02 (m, 1H), 4.31-4.48 (m, 3H), 5.38 (s, 2H), 5.50 (d, 1H), 7.17 (d, 1H), 7.33 (t, 2H), (7.60 (dd, 1H), 7.74 ( t, 1H), 7.83 (s, 1H), 8.02 (s, 1H), 8.20 (t, 1H), 8.48 (s, 1H), 9.17 (s, 1H), 9.85 (s, 1H); MH * 529.9, Example 73 (2R) -N-. {(1R) -2 - [(4. {[3-Chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino]} quinazolin-5-yl) oxy] -1-methylethyl.} -2,4-dihydroxybutanamide The procedure described in Example 63 is repeated using 5- { [(2R.}. -2-aminopropyl] oxy .} -? / - [3-chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] quinazolin-4-amine and (R) - (+) - a-hydroxy-γ-butyrolactone to give the title compound in 73% yield: NMR spectrum (DMSO-d6) 1.22 (d, 3H), 1.46-1.61 (m, 1H), 1.72-1.87 (m, 1H), 3.40-3.54 (m, 2H), 3.84-3.97 (m, 1H), 4.19-4.41 (m, 3H), 4.42-4.58 (m, 1H), 5.35 (s, 2H), 5.40 (d, 1H), 7.14 (d, 1H), 7.25- 7.38 (m, 2H), 7.53 (dd, 1H), 7.72 (t, 1H), 7.80 (d, 1H), 7.92-8.05 (, 2H), 8.47 (s, 1H), 9.14 (d, 1H), 9.75 (s, 1H); Mass Spectrum MH * 543.9. 5-. { [(2R) -2-aminopropyl] oxy} -? / - [3-Chloro-4- (1,3-thiazol-4-methoxy) phenyl] quinazolin-4-amine used as starting material is prepared as follows: The procedure described in Example 3 (preparation of materials initial) is repeated using 2-chloro-4 - [(5-fluoroquinazolin-4-yl) amino] phenol (obtained as described in Example 4.5, preparation of starting materials) and (2R) -2-aminopropan-1- ol to give 4- (5-. {[[(2R) -2-aminopropyl] oxy} quinazolin-4-yl) amino] -2-chlorophenol in 100% yield; NMR spectrum (DMSO-d6) 1.16 (d, 3H), 3.29-3.44 (m, 1H), 3.98 (dd, 1H), 4.22 (dd, 1H), 6.96 (d, 1H), 7.09 (d, 1H) , 7.30 (d, 1H), 7.58 (dd, 1H), 7.69 (t, 1H), 8.10 (d, 1H), 8.47 (s, 1H) (4 interchangeable); Mass Spec. MH * 344.9.

The procedure described in Example 65 (preparation of starting materials) is repeated using 4 - [(5- {[[2R) -2-aminopropyl] oxy} quinazolin-4-yl) amino] -2-chlorophenol and 4- (chloromethyl) -l, 3-thiazole hydrochloride gives 5-. { [(2R) -2-aminopropyl] oxy} -? / - [3-chloro-4- (1, 3-thiazol-4-ylmethoxy) phenyl] quinazolin-4-amine in 65% yield; NMR spectrum (DMSO-d6) 1.17 (d, 3H), 3.33-3.45 (m, 1H), 4.00 (dd, 1H), 4.24 (dd, 1H), 5.32 (s, 2H), 7.11 (d, 1H) , 7.30 (d, 1H), 7.33 (d, 1H), 7.67-7.82 (m, 3H), 8.23 (d, 1H), 8.51 (s, 1H), 9.14 (d, 1H); Mass Spectrum MH * 441.9. Example 74 (2S) - / V-. { (1R) -2 - [(4- {[3-Chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methylethyl} -2,4-dihydroxybutanamide The procedure described in Example 63 is repeated using 5-. { [(2R) -2-aminopropyl] oxy} - / V- [3-chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] quinazolin-4-amine (obtained as described in Example 73, preparation of starting materials) and (S) - ( -) - a-hidroxi -? - buíirolacfona to give the compound of the title in 58% production; NMR spectrum (DMSO-d6) 1.23 (d, 3H), 1.27-1.40 (m, 1H), 1.60-1.62 (m, 1H), 3.33-3.46 (m, 2H), 3.87-3.97 (m, 1H), 4.19-4.41 (, 3H), 4.42-4.58 (m, 1H), 5.35 (s, 2H), 5.40 (d, 1H), 7.14 (d, IH), 7.25-7.38 (m, 2H), 7.53 (dd) , 1 H), 7.72 (t, 1 H), 7.80 (d, 1 H), 7.92-8.05 (m, 2H), 8.47 (s, 1 H), 9.14 (d, 1 H), 9.75 (s, 1 HOUR); Mass Spectrum MH * 543.9. Example 75? / - ethyl-? F-. { 2 - [(4- {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide The procedure described in Example 3 is repeated using 2- (chloromethyl) pyridine and? / - [2- (. {4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin-5-yl. ) ethyl] - / V-methylacetamide to give the title compound as a white solid in 1 1% yield; NMR spectrum (DMSO-d6 373K) 1.94 (s, 3H), 2.28 (s, 3H), 3.00 (s, 3H), 3.88 (t, 2H), 4.46 (m, 2H), 5.20 (s, 2H) ), 7.01 (d, 1 H), 7.16 (d, 1 H), 7.34 (m, 2 H), 7.51 (m, 2 H), 7.55 (d, 1 H), 7.68 (t, 1 H), 7.83 ( td, 1 H), 8.41 (s, 1 H), 8.58 (d, 1 H), 9.63 (s, 1 H); Mass Spectrum MH * 458.? / - [2- ( { 4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin-5-yl.}. Oxy) ethyl] -? / - mefilacetamide used as Initial material is prepared as follows: The procedure described in Example 3 (preparation of starting materials) is repeated using acetic acid and 2-methyl-4- (. {5- [2- (methylamino) ethoxy] quinazolin-4- il.}. amino) phenol (obtained as described in Example 3, preparation of starting materials) to give? / - [2- (. {4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin- 5-yl.} Oxy) ethyl] -? / - mephilaceiamide as a light brown solid in 100% yield; NMR spectrum (DMSO-d6) 1.90 (s, 3H), 2.16 (s, 3H), 3.02 (s, 3H), 3.85 (t, 2H), 4.45 (i, 2H), 6.82 (d, 1H), 7.18 (dd, 1H), 7.25 (d, 1H), 7.34 (m, 2H), 7.92 (t, 1H), 8.65 (s, 1H), 9.45 (s, 1H), 10.52 (s, 1H); Mass Spec. MH * 367. Example 76 W-Methyl-? F-. { 2 - [(4- {[3-methyl-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide The procedure described in Example 3 is repeated using 4- (chloromethyl) -1,3-thiazole and? / - [2- (. {4 - [(4-hydroxy-3-methylphenyl) amino] qu Nazolin-5-yl.}. oxy) ethyl] -? / - mefilaceiamide (obtained as described in Example 75, preparation of starting materials) to give the title compound as an off-white solid in 5% yield; NMR spectrum (DMSO-d6373K) 1.94 (s, 3H), 2.24 (s, 3H), 2.99 (s, 3H), 3.87 (t, 2H), 4.46 (m, 2H), 5.25 (s, 2H), 7.08 (d, 1H), 7.17 (d, 1H), 7.35 (d, 1H), 7.47 (d, 1H), 7.54 (dd, 1H), 7.70 (m, 2H), 8.41 (s, 1H), 9.07 ( d, 1H), 9.63 (s, 1H); Mass Spectrum MH * 464. Example 77 W-ethyl-? R- (2- {[[4- ( { 3-methyl-4 - [(5-methylisoxazol-3-yl) methoxy] phenyl} amino) quinazolin-5-yl] oxy} ethyl) acetamide The procedure described in Example 3 is repeated using 3- (chloromethyl) -5-methylisoxazole and? / - [2- (. {4 - [(4-hydroxy-3-meilyphenyl) amino] quinazolin-5-yl} oxy) ethyl] -? / - methylacetamide (obtained as described in Example 75, preparation of starting materials) to give the title compound as a white solid in 14% yield; NMR spectrum (DMSO-d6 373K) 1.95 (s, 3H), 2.23 (s, 3H), 2.43 (s, 3H), 3.57 (s, 3H), 3.88 (t, 2H), 4.47 (m, 2H) ), 5.15 (s, 2H), 6.29 (s, 1 H), 7.05 (d, 1 H), 7.15 (d, 1 H), 7.34 (d, 1 H), 7.48 (d, 1 H), 7.54 (dd, 1 H), 7.69 (1, 1 H), 8.42 (s, 1 H), 9.64 (s, 1 H); Mass Spectrum MH * 462. Example 78 2-Hydroxy-W-methyI-W-. { 2 - [(4- {[3-methyl-4- (1, 3-thiazol-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide The procedure described in Example 3 is repeated using 2- (chloromethyl) -1,3-yiazole and 2-hydroxy- / V- [2- (. {4 - [(4-hydroxy-3-methylphenyl) amino]] quinazoln-5-yl.} oxy) ethyl] -? / - meyilaceiamide (obtained as described in Example 3, preparation of starting materials) to give the title compound as a white solid in 38% yield; NMR spectrum (DMSO-d6 373K) 2.27 (s, 3H), 2.98 (s, 3H), 3.91 (t, 2H), 4.07 (s, 2H), 4.47 (t, 2H), 5.44 (s, 2H), 7.09 (d, 1H), 7.16 (d, 1H), 7.34 (d, 1H), 7.54 (m, 2H), 7.67 (t, 1H), 7.70 (d, 1H), 7.83 (d, 1H), 8.41 (s, 1H), 9.63 (s, 1H); Mass Spec. MH * 480. Example 79 2-Hydroxy- / -. { 2 - [(4- {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyI] amino} quinazolin-5-yl) oxy] ethyl} acetamide The procedure described in Example 3 is repeated using 2- (chloromethyl) pyridine and 2-hydroxy-A / - [2- (. {4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin-5-yl) .}. oxy) ethyl] acetamide to give the title compound as a yellow solid in 27% yield; NMR spectrum (DMSO-d6) 2.27 (s, 3H), 3.71 (q, 2H), 3.77 (d, 2H), 4.38 (t, 2H), 5.20 (s, 2H), 5.49 (t, 1H), 6.98 (d, 1H), 7.14 (d, 1H), 7.31 (d, 1H), 7.35 (dd, 1H), 7.45 (d, 1H), 7.56 (m, 2H), 7.68 (i, 1H), 7.85 (d, td, 1H), 8.17 (t, 1H), 8.41 (s, 1H), 8.57 (d, 1H), 9.75 (s, 1H); Mass Spectrum MH * 460. 2-hydroxy -? / - [2- (. {4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin-5-yl} oxy) ethyl] acetamide used as starting material is prepared as follows The procedure described in Example 3 (preparation of starting materials) is repeated using ethanolamine and 4 - [(5-fluoroquinazolin-4-yl) amino] -2-methylphenol (obtained as described in Example 3, preparation of materials initials) to give 4-. { [5- (2-aminoethoxy) quinazolin-4-yl] amino} -2-methylphenol as a gray solid in 23% yield; NMR spectrum (DMSO-d6) 2.14 (s, 3H), 3.09 (d, 2H), 3.28 (s, 2H), 4.25 (t, 2H), 6.77 (d, 1 H), 7.08 (d, 1 H) , 7.28 (d, 1 H), 7.46 (dd, 1 H), 7.55 (d, 1 H), 7.66 (t, 1 H), 8.40 (s, 1 H), 10.31 (s, 1 H); Mass Spectrum M H * 31 1. The procedure described in Example 3 (preparation of starting materials) is repeated using glycolic acid and 4-. { [5- (2-aminoethoxy) quinazolin-4-yl] amino} -2-methylphenol to give 2-hydroxy- / V- [2- (. {4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin-5-yl} oxy) ethyl] acetamide as a solid light coffee at 58% production; NMR spectrum (DMSO-d6) 2.16 (s, 3H), 3.69 (q, 2H), 3.76 (d, 2H), 4.43 (t, 2H), 6.82 (d, 1 H), 7.30 (m, 4H), 7.90 (t, 1 H), 8.20 (t, 1 H), 8.66 (s, 1 H), 9.42 (s, 1 H), 10.55 (s, 1 H); Mass Spectrum MH * 369. Example 80 2-Hydroxy- V-. { 2 - [(4- {[3-methyl-4- (1, 3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy} ethyl} acetamide The procedure described in Example 3 is repeated using 4- (chloromethyl) -1,3-thiazole and 2-hydroxy- / V- [2- (. {4 - [(4-hydroxy-3-methylphenyl) amino]] quinazolin-5-yl.} oxy) efil] acetamide (obtained as described in Example 79, preparation of starting materials) to give the title compound as a yellow solid in 21% yield; NMR spectrum (DMSO-d6) 2.20 (s, 3H), 3.71 (q, 2H), 3.77 (d, 2H), 4.38 (t, 2H), 5.23 (s, 2H), 5.49 (t, 1H), 7.08 (d, 1H), 7.13 (d, 1H), 7.32 (d, 1H), 7.44 (d, 1H), 7.57 (d, 1H), 7.69 (t, 1H), 7.77 (d, 1H), 8.17 ( t, 1H), 8.42 (s, 1H), 9.14 (d, 1H), 9.77 (s, 1H); Mass Spectrum MH * 466. Example 81 W-. { 2 - [(4- {[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1,1-dimethylethyl} -2-hydroxyacetamide The procedure described in Example 3 is repelled using 2- (chloromethyl) pyridine and 2-hydroxy -? / - [2- (. {4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin-5-yl) .}. oxy) -1,1-dimethylethyl acetamide to give the title compound as a white solid in 16% yield; NMR spectrum (DMSO-d6) 1.46 (s, 6H), 3.72 (d, 2H), 4.42 (s, 2H), 5.27 (s, 2H), 5.34 (t, 1H), 7.16 (d, 1H), 7.24 (d, 1H), 7.37 (m, 2H), 7.50 (m, 2H), 7.58 (d, 1H), 7.73 (i, 1H), 7.87 (td, 1H), 8.06 (d, 1H), 8.50 ( s, 1H), 8.59 (d, 1H), 9.83 (s, 1H); Mass Spectrum MH * 508. 2-hydroxy -? / - [2- ( { 4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin-5-yl.} Oxy) -1, 1- dimethyryl] acelamide as the initial material is prepared as follows: The procedure described in Example 3 (preparation of starting materials) is repeated using 2-amino-2-methylpropan-1-ol and 4 - [(5-fluoroquinazolin-4-) il) amino] -2-methylphenol (obtained as described in Example 3, preparation of starting materials) to give 4-. { [5- (2-amino-2-meilypropoxy) quinazolin-4-yl] amino} -2-meitylphenol as a white solid in 78% yield; NMR spectrum (DMSO-d6) 1.34 (s, 6H), 4.23 (s, 2H), 6.97 (d, 1H), 7.18 (d, 1H), 7.35 (d, 1H), 7.52 (dd, 1H), 7.73 (t, 1H), 7.96 (d, 1H), 8.46 (s, 1H), 10.50 (s, 1H); Mass Spectrum MH * 360. The procedure described in Example 3 (preparation of starting materials) is repeated using glycolic acid and 4-. { [5- (2-amino-2-methylpropoxy) quinazolin-4-yl] amino} -2-methylphenol to give 2-hydroxy -? / - [2- ( { 4 - [(4-hydroxy-3-mephylphenyl) amino] quinazolin-5-yl.} Oxy) -1,1-dimetic Leti] acetamide as a light brown solid in 53% yield; NMR spectrum (DMSO-d6) 1.47 (s, 6H), 3.69 (d, 2H), 4.47 (s, 2H), 7.04 (d, 1H), 7.38 (m, 3H), 7.78 (d, 1H), 7.96 (t, 1H), 8.18 (t, 1H), 8.80 (s, 1H), 10.40 (s, 1H), 10.67 (s, 1H); Mass Spectrum MH * 417. Example 82 2 «Hydroxy-N-. { (2Rj-2 - [(4- {[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide The procedure described in Example 3 is repeated using 2- (chloromethyl) pyridine and 2-hydroxy-N - [(2R) -2- (. {4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin -5-yl.}. Oxy) propyl] acetamide to give the title compound as a white solid in 29% yield; NMR spectrum (DMSO-d6) 1.40 (d, 3H), 2.27 (s, 3H), 3.43 (dt, 1H), 3.72 (d, 1H), 3.80 (d, 2H), 4.94 (m, 1H), 5.20 (s, 2H), 5.46 (t, 1H), 7.00 (d, 1H), 7.21 (d, 1H), 7.30 (d, IH), 7.34 (dd, 1H), 7.56 (m, 3H), 7.68 (d, t, 1H), 7.85 (td, 1H), 8.16 (t, 1H), 8.43 (s, 1H), 8.58 (d, 1H), 9.94 (s, 1H); Mass Spectrum MH * 474. 2-hydroxy-N- / Y2R) -2- ( {4 - [(4-hydroxy-3-meilyphenyl) amino] quinazolin-5-yl}. Oxy) propyl] aceylamide used as starting material is prepared as follows: The procedure described in Example 3 (preparation of starting materials) is repeated using (R) - (-) - 1-amino-propan-2-ol and 4 - [(5-fluoroquinazolin -4-yl) amino] -2-methylphenol (obtained as described in Example 3, preparation of starting materials) to give 4- (. {5 - [(1R) -2-amino-1-methylethoxy] quinazolin -4-yl.}. Amino) -2-methylphenol as a brown solid in 65% yield; NMR spectrum (DMSO-d6) 1.39 (d, 3H), 2.16 (s, 3H), 2.96 (m, 2H), 3.30 (s, 2H), 4.96 (m, 1H), 6.77 (d, 1H), 7.14 (d, 1H), 7.25 (d, 1H), 7.44 (dd, 1H), 7.51 (d, 1H), 7.67 (t, 1H), 8.39 (s, 1H), 9.16 (s, 1H), 10.50 ( s, 1 H); Mass Spec. MH * 325. The procedure described in Example 3 (preparation of starting materials) is repeated using glycolic acid and 4- (. {5- [ { 1R) -2-amino-1-mephylefoxy] quinazoline. -4-il} amino) -2-methylphenol to give 2-hydroxy-N - [(2R) -2- (. {4- [. {4-hydroxy-3-mephylphenyl) amino] quinazolin-5-ii} oxy) propyl] aceylamide as a dark brown solid in 59% yield; Specimen NMR (DMSO-d6) 1.41 (d, 3H), 2.17 (s, 3H), 3.43 (df, 1H), 3.75 (dt, 1H), 3.78 (s, 2H), 5.01 (m, 1H), 6.84 (d, 1H), 7.30 (d, 1H), 7.32 (dd, 1H), 7.39 (d, 1H), 7.46 (d, 1H), 7.95 (t, 1H), 8.22 (i, 1H), 8.75 ( s, 1H), 9.54 (d, 1H), 10.78 (s, 1H); Mass Spec. MH * 383. Example 83 2-Hydroxy-? F-. { (2R) -2 - [(4- {[3-methyl-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide The procedure described in Example 3 is repeated using 4- (chloromethyl) -1,3-thiazoI and 2-hydroxy -? / - [(2R) -2- (. {4 - [(4-hydroxy-3) -methylphenyl) amino] quinazolin-5-yl.} oxy) propyl] acetamide (obtained as described in Example 82, preparation of starting materials) to give the thiful compound as a white solid in 13% yield; NMR spectrum (DMSO-d6 1.39 (d, 3H), 2.21 (s, 3H), 3.42 (dt, 1H), 3.71 (dt, 1H), 3.79 (d, 2H), 4.95 (m, 1H), 5.24 ( s, 2H), 5.48 (t, 1H), 7.09 (d, 1H), 7.23 (d, 1H), 7.29 (d, 1H), 7.54 (d, 1H), 7.62 (dd, 1H), 7.68 (t , 1H), 7.77 (d, 1H), 8.16 (t, 1H), 8.44 (s, 1H), 9.14 (d, 1H), 9.95 (s, 1H); Mass Spectrum MH * 480. Example 84 W- ((2R) -2- { [4- ( { 4 - [(3-Fluorobenzyl) oxy] -3-methylphenyl}. Amino) quinazolin-5-yl] oxy} propyl) -2 -hydroxyacetamide The procedure described in Example 3 is repelled using 1- (chloromethyl) -3-fluorobenzene and 2-hydroxy -? / - [(2R) -2- (. {4 - [(4-hydroxy-3-methylphenyl)) amino] quinazolin-5-yl.}. oxy) propyl] acetamide (obtained as described in Example 82, preparation of starting materials) to give the title compound as a light yellow solid in 25% yield; NMR spectrum (DMSO-d6) 1.39 (d, 3H), 2.25 (s, 3H), 3.42 (dt, 1H), 3.72 (d, 1H), 3.81 (d, 2H), 4.94 (m, 1H), 5.17 (s, 2H), 5.47 (t, 1H), 6.99 (d, 1H), 7.16 (td, 1H), 7.22 (d, 1H), 7.30 (m, 3H), 7.43 (m, 1H), 7.56 (d, 1H), 7.61 (dd, 1H), 7.68 (t, 1H), 8.16 (t, 1H), 8.43 (s, 1H), 9.94 (s, 1H); Mass specifier MH * 491. Example 85 2-Hydroxy-f-. { (2R) -2 - [(4- {[3-methyI-4- (1,3-thiazol-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide The procedure described in Example 3 is repeated using 2- (chloromethyl) -1,3-thiazole and 2-hydroxy -? / - [(2R) -2- (. {4 - [(4-hydroxy-3- methylphenyl) amino] quinazolin-5-yl.} oxy) propyl] acetamide (obtained as described in Example 82, preparation of starting materials) to give the title compound as a light brown solid in 31% yield; NMR spectrum (DMSO-d6) 1.39 (d, 3H), 2.25 (s, 3H), 3.42 (dt, 1H), 3.73 (m, 1H), 3.79 (d, 2H), 4.94 (m, 1H), 5.44 (s, 2H), 5.47 (f, 1H), 7.09 (d, 1H), 7.23 (d, 1H), 7.30 (d, 1H), 7.58 (d, 1H), 7.63 (dd, 1H), 7.69 (d, t, 1H), 7.77 (d, 1H), 7.84 (d, 1H), 8.16 (t, 1H), 8.43 (s, 1H), 9.96 (s, 1H); Mass Spectrum MH * 480. Example 86 W-. { (2R) -2 - [(4- {[[3-ethyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinozoln-5-yl) oxy] propyl} acetamide The procedure described in Example 3 is repeated using 2- (chloromethyl) pyridine and? / - [(2R) -2- (. {4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin-5-yl) .}. ox.) propyl] acetamide to give the title compound as a white solid in 43% yield; NMR spectrum (DMSO-d6) 1.41 (d, 3H), 1.77 (s, 3H), 2.27 (s, 3H), 3.41 (d, 1H), 3.58 (dt, 1H), 4.87 (m, 1H), 5.20 (s, 2H), 7.01 (d, 1H), 7.22 (d, 1H), 7.29 (d, 1H), 7.35 (dd, 1H), 7.55 (m, 2R), 7.58 (dd, 1H), 7.69 (d, t, 1H), 7.85 (td, 1H), 8.23 (t, 1H), 8.45 (s, 1H), 8.58 (d, 1H), 9.97 (s, 1H); Mass Spectrum MH * 458.? / - [(2H) -2- ( { 4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin-5-yl.}. Oxy) propyl] acetamide used as Initial material is prepared as follows: The procedure described in Example 3 (preparation or initial materials) is repeated using acetic acid and 4- (. {5 - [(1R) -2-amino-1-methylethoxy] quinazoline-4 -yl.}. amino) -2-methylphenol (obtained as described in Example 82, preparation of starting materials) to give? / - [(2R) -2- (. {4 - [(4-hydroxy) 3-methylphenyl) amino] quinazolin-5-yl.}. Oxy) propyl] acetamide as a ginger solid in 90% yield; NMR spectrum (DMSO-d6) 1.41 (d, 3H), 1.76 (s, 3H), 2.17 (s, 3H), 3.41 (d, 1H), 3.62 (dt, 1H), 4.96 (m, 1H), 6.85 (d, 1H), 7.31 (d, 1H), 7.36 (m, 2H), 7.49 (d, 1H), 7.96 (t, 1H), 8.24 (t, 1H), 8.77 (s, 1H), 9.57 ( s, 1H), 10.77 (s, 1H); Mass Spectrum MH * 367. Example 87? V-. { (2R) -2 - [(4- {[[3-ethyl-4- (1,3-thiazole-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide The procedure described in Example 3 is repeated using 4- (chloromethyl) -1,3-thiazole and? / - [(2R) -2- (. {4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin-5-yl.}. oxy) propyl] acetamide (obtained as described in Example 86, preparation of starting materials) to give the title compound as a white solid in 20% yield; NMR spectrum (DMSO-d6) 1.41 (d, 3H), 1.78 (s, 3H), 2.23 (s, 3H), 3.41 (d, 1H), 3.58 (dt, 1H), 4.87 (m, 1H), 5.25 (s, 2H), 7.11 (d, 1H), 7.21 (d, 1H), 7.29 (d, 1H), 7.53 (d, 1H), 7.63 (dd, 1H), 7.69 (t, 1H), 7.76 ( d, 1H), 8.23 (t, 1H), 8.44 (s, 1H), 9.14 (d, 1H), 9.96 (s, 1H); Mass Spectrum MH * 464. Example 88? M (2R) -2-. { [4- ( { 4 - [(3-Fluorobenzyl) oxy] -3-methylphenyl}. Amino) quinazolin-5-yl] oxy} propyl) acetamide The procedure described in Example 3 is repeated using 1- (chloromethyl) -3-fluorobenzene and? / - [(2R) -2- (. {4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin- 5-yl.} Oxy) propyl] acetamide (obtained as described in Example 86, preparation of starting materials) to give the compound of the like as a white solid in 46% yield; Specimen NMR (DMSQ-d6) 1.41 (d, 3H), 1.77 (s, 3H), 2.26 (s, 3H), 3.41 (d, 1H), 3.58 (dt, 1H), 4.86 (m, 1H), 5.18 (s, 2H), 7.01 (d, 1H), 7.16 (td, 1H), 7.22 (d, 1H), 7.30 (m, 3H), 7.42 (m, 1H), 7.54 (d, 1H), 7.62 (d, dd, 1H), 7.68 (t, 1H), 8.22 (t, 1H), 8.43 (s, 1H), 9.95 (s, 1H); Mass Spectrum MH * 475. Example 89 / V-. { (2R) -2 - [(4- {[3-Methyl-4- (1,3-thiazol-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide The procedure described in Example 3 is repeated using 2- (chloromethyl) -1,3-fiazole and? / - [(2R) -2- (. {4 - [(4-hydroxy-3-methylphenyl) amino] ] quinazolin-5-yl.}. oxy) propyl] acetamide (obtained as described in Example 86, preparation of starting materials) to give the title compound as a light brown solid in 25% yield; NMR spectrum (DMSO-d6) 1.41 (d, 3H), 1.77 (s, 3H), 2.25 (s, 3H), 3.42 (d, 1H), 3.60 (dt, 1H), 4.88 (m, 1H), 5.45 (s, 2H), 7.11 (d, 1H), 7.22 (d, 1H), 7.31 (d, 1H), 7.56 (d, 1H), 7.63 (dd, 1H), 7.68 (t, 1H), 7.76 ( d, 1H), 7.83 (d, 1H), 8.23 (t, 1H), 8.43 (s, 1H), 9.97 (s, 1H); Mass Spectrum MH * 464. EXAMPLE 90 2-Hydroxy-f-methyl-? / -. { (2R) -2 - [(4- {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide The procedure described in Example 3 is repeated using 2- (chloromefil) pyridine and 2-hydroxy -? / - [(2R) -2- (. {4 - [(4-hydroxy-3-meitylphenyl) amino] quinazolin -5-yl.}. Oxy) propyl) -? / - methylacetamide to give the title compound as a light yellow solid in 17% yield; NMR spectrum (DMSO-d6 373K) 1.43 (d, 3H), 2.29 (s, 3H), 2.97 (s, 3H), 3.58 (m, 1H), 4.08 (m, 3H), 5.11 (m, 1H), 5.19 (s, 2H), 7.01 (d, 1H), 7.21 (d, 1H), 7.32 (m, 2H), 7.57 (m, 3H), 7.67 (i, 1H), 8.83 (td, 1H), 8.41 (s, 1H), 8.57 (d, 1H), 9.81 (s, 1H); Mass Spectrum MH * 488. 2-hydroxy-N - [(2R) -2- (. {4 - [(4-hydroxy-3-methylphenyl) amino] quinazoln-5-yl.} Oxy) propyl] -? / - methylacetamide used as starting material is prepared as follows: The procedure described in Example 3 (preparation of initial materials) is repeated using (2R) -1- [allyl (methyl) amino] propan-2-ol (obtained as described in Example 2.3, preparation of initial materials) and 4 - [(5-fluoroquinazolin-4-yl) amino] -2-methylphenol (obtained as described in Example 3, preparation of starting materials) for give 4 - [(5- { (1) -2- [allyl (methyl) amino] -1-methylethoxy.} quinazolin-4-yl) amino] -2-methylphenol as a brown oil in 86% yield; NMR spectrum (DMSO-d6) 1.43 (d, 3H), 2.15 (s, 3H), 2.18 (s, 3H), 2.54 (d, 1H), 2.88 (dd, 1H), 3.00 (m, 2H), 4.92 (m, 1H), 5.01 (d, 1H), 5.11 (d, 1H), 5.62 (m, 1H), 6.77 (d, 1H), 7.16 (d, 1H), 7.26 (d, 1H), 7.35 ( s, 1H), 7.38 (d, 1H), 7.66 (t, 1H), 8.37 (s, 1H), 9.17 (s, 1H), 10.16 (s, 1H); Mass Spectrum MH * 379. The procedure described in Example 2.3 (preparation of starting materials) is repeated using chlorotris (triphenylphosphine) rhodium (l) and 4 - [(5- {(1R) -2- [allyl ( methyl) amino] -1-methylethoxy.] quinazolin-4-yl) amino] -2-methylphenol to give 2-methyl-4- (. {5 - [(1R) -1-methyl-2- (meitylamino) ) efoxy] quinazolin-4-yl.}. amino) -phenol as a brown foam in 56% yield; NMR spectrum (DMSO-d6) 1.41 (d, 3H), 2.15 (s, 3H), 2.33 (s, 3H), 2.87 (m, 2H), 4.85 (m, 1H), 6.77 (el, 1H), 7.14 (d, 1H), 7.25 (d, 1H), 7.43 (s, 1H), 7.46 (d, 1H), 7.64 (t, 1H), 8.38 (s, 1H), 9.14 (s, 1H), 10.35 ( s, 1 H); Mass Spectrum MH * 339. The procedure described in Example 3 (preparation of starting materials) is repeated using glycolic acid and 2-methyl-4- (. {5 - [(1R) -1-methyl-2- ( methylamino) ethoxy] quinazolin-4-yl.}. amino) phenol to give 2-hydroxy-N - [(2R) -2- (. {4 - [(4-hydroxy-3-methyl-methyl) amy no ] quinazolin-5-yl.}. oxy) propyl] -? / - methylacetamide as an orange solid in 81% yield; NMR spectrum (DMSO-d6) 1.38 (d, 3H), 2.15 (s, 3H), 2.96 (s, 3H), 3.35 (d, 1H), 4.02 (s, 2H), 4.21 (m, 2H), 5.18 (m, 1H), 6.83 (d, 1H), 7.27 (m, 1H), 7.38 (s, 1H), 7.46 (d, 1H), 7.92 (t, 1H), 8.70 (s, 1H), 9.52 ( s, 1H), 10.68 (s, 1H) Mass Spectrum MH * 397. Example 91 2-Hydroxy-methyl- / V-. { (2R) -2 - [(4- {[3-methyl-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide The procedure described in Example 3 is repeated by using 4- (chloromethyl) -1,3-thiazole and 2-hydroxy -? / - [(2R) -2- (. {4 - [(4-hydroxy-3-) methylphenyl) amino] quinazolin-5-yl}. oxy) propyl] -? / - mefilacetamide (obtained as described in Example 90, preparation of starting materials) to give the title compound as a white solid in a yellow solid. % production; NMR spectrum (DMSO-d6 373K) 1.43 (d, 3H), 2.24 (s, 3H), 2.97 (s, 3H), 3.57 (m, 1H), 4.07 (m, 3H), 5.13 (m, 1H), 5.25 (s, 2H), 7.09 (d, 1H), 7.11 (d, 1H), 7.34 (d, 1H), 7.57 (m, 2H), 7.69 (m, 2H), 8.42 (s, 1H), 9.07 (d, 1H), 9.82 (s, 1H); Mass Spectrum MH * 494. Example 92 2-Hydroxy-? / - methyl-? R - ((2R) -2- { [4- (. {3-methyl-4 - [(5-methylisoxazole- 3-yl) methoxy] phenyl.}. Amino) quinazolin-5-yl) oxy} propyl) acetamide The procedure described in Example 3 is repeated using 3- (chloromethyl) -5-methylisoxazole and 2-hydroxy -? / - [(2R) -2- (. {4 - [(4-hydroxy-3-methylphenyl)) amino] quinazolin-5-yl.}. oxy) propyl] -? / - methylacetamide (obtained as described in Example 90, preparation of starting materials) to give the title compound as a white solid in 7% yield; NMR spectrum (DMSO-d6 373K) 1.44 (d, 3H), 2.22 (s, 3H), 2.42 (s, 3H), 2.98 (s, 3H), 3.58 (m, 1 H), 4.17 (m, 3H), 5.1 1 (m, 1 H), 5.15 (s, 2H), 6.29 (s, 1 H), 7.07 (d, 1 H), 7.1 1 (d, 1 H), 7.33 (d, 1 H) ), 7.57 (m, 2H), 7.69 (t, 1 H), 8.44 (s, 1 H), 9.83 (s, 1 H); Mass Spec. MH * 492. Example 93 / - ethyl-? V-. { (1 R) -1-methyl-2 - [(4. {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide The procedure described in Example 3 is repeated using 2- (chloromethyl) pyridine and? / - [(1R) -2- (. {4 - [(4-hydroxy-3-methylphen I) am i no] quinazolin- 5-yl.}. Oxy) -1-methyl ethyl l] -? / - methyl acetamide to give the title compound as a light beige solid in 43% yield; NMR spectrum (DMSO-d6 373K) 1.21 (d, 3H), 1.85 (s, 3H), 2.27 (s, 3H), 2.84 (s, 3H), 4.34 (m, 1H), 4.40 (t, 1H), 5.07 (m, 1H), 5.20 (s, 2B), 7.01 (d, 1H), 7.17 (d, 1H), 7.33 (m, 2H), 7.42 (d, 1H), 7.47 (dd, 1H), 7.55 (d, 1H), 7.67 (t, 1H), 7.82 (td, 1H), 8.41 (s, 1H), 8.57 (d, 1H), 9.50 (s, 1H); Mass Spectrum MH * 472.? / - [(1 R) -2- ( { 4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin-5-yl.] Oxy) -1- methylethyl] -? / - methylacetamide used as starting material is prepared as follows: The procedure described in Example 3 (preparation of starting materials) is repeated using (2R) -2- (methylamino) propan-1-ol (obtained as described in Becker et al, J. Chem. Soc. 1957, 858) and 4 - [(5-fluoroquinazolin-4-yl) amino] -2-methylphenol (obtained as described in Example 3, preparation of starting materials) to give 2-methyl-4 - [(5- { [(2R) -2- (methylamino) propyl] oxy}. qu. mallow I in-4- l) amino] phenol as a brown solid. in 80% production; NMR spectrum (DMSO-d6) 1.16 (d, 3H), 2.14 (s, 3H), 2.34 (s, 3H), 3.04 (m, 1H), 3.24 (bs, 1H), 4.08 (dd, 1H), 4.25 (dd, 1H), 6.76 (d, 1H), 7.06 (d, 1H), 7.26 (d, 1H), 7.47 (d, 1H), 7.53 (dd, 1H), 7.65 (t, 1H), 8.39 ( s, 1H), 9.17 (s, 1H), 10.37 (s, 1H); Mass Spectrum: MH * 339. To a mixture of triethylamine (420 μl) and 2-methyl-4 - [(5 { [(2R) -2- (methylamino) propyl] oxy]. Quinazolin-4-yl) amino] Phenol (450 mg) in DCM (5 ml) is added acetyl chloride (1 90 μl). The reaction was stirred for 30 minutes and then quenched with water and exuted with DCM (x2). The residue is dissolved in 7N MeOH / NH3 and stirred at room temperature for 30 minutes. Solvent is removed in vacuo and water is added. The mixture is extracted with DCM (x2), filtered and then the solvent is removed to give? / - [(1 R) -2- (. {4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin- 5-yl.} Oxy) -1-methylethyl] -? / - methylacetamide as a pink foam (365 mg, 72%); NMR spectrum (DMSO-d6 373K) 1.41 (d, 3H), 1.86 (s, 3H), 2.17 (s, 3H), 2.83 (s, 3H), 4.36 (m, 2H), 5.04 (m , 1 H), 6.77 (d, 1 H), 7.1 6 (d, 1 H), 7.29 (m, 3 H), 7.67 (t, 1 H), 8.38 (s, 1 H), 8.78 (s, 1 H), 9.43 (s, 1 H); Mass Spectrum MH * 381. Example 94? F-Methyl- / -. { (1 R) -1-methyl-2 - [(4- {[3-methyl-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide The procedure described in Example 3 is repeated using 4- (chloromethyl) -1,3-thiazole and? / - [(1 R) -2- (. {4 - [(4-hydroxy-3-methylphenyl)) amino] quinazolin-5-yl.}. oxy) -1-methyethyl] -? / - methylacetamide (obtained as described in Example 93, preparation of starting materials) to give the title compound as a white solid in 13% production; NMR spectrum (DMSO d6373K) 1.22 (d, 3H), 1.86 (s, 3H), 2.24 (s, 3H), 2.85 (s, 3H), 4.33 (m, 1H), 4.42 (t, 1H), 5.09 ( m, 1H), 5.25 (s, 2H), 7.09 (d, 1H), 7.18 (d, 1H), 7.34 (d, 1H), 7.39 (s, 1H), 7.50 (d, 1H), 7.70 (m , 2H), 8.41 (s, 1H), 9.08 (s, 1H), 9.51 (s, 1H); Mass Spectrum MH * 478. Example 95? F-. { (1R) -2 - [(4- {[3-Chloro-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methylethyl} -2-rtidroxy- / V-methylacetamide The procedure described in Example 3 is repeated using 4- (chloromethyl) -1,3-thiazole and? / - [(1R) -2- (. {4 - [(3-chloro-4-hydroxyphenyl) amino] quinazolin-5-yl.} oxy) -1-methyl-ethyl] -2-hydroxy-β-methylacetamide (obtained as described in Example 54, preparation of starting materials) to give the title compound as a white solid in 64% production; NMR spectrum (DMSO-d6 373K) 1.25 (d, 3H), 2.83 (s, 3H), 3.98 (s, 2H), 4.34 (m, 1H), 4.47 (t, 1H), 4.98 (m, 1H), 5.34 (s, 2H), 7.19 (d, 1H), 7.37 (d, 2H), 7.51 (dd, 1H), 7.70 (t, 1H), 7.74 (d, 1H), 7.93 (d, 1H), 8.46 (s, 1H), 9.08 (s, 1H), 9.57 (s, 1H); Mass Spectrum MH * 514.

Example 96 2-Hydroxy-r-methyl-yV-. { (1 R) -1-methyl-2 - [(4. {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] etl} acetamide The procedure described in Example 3 is repeated using 2- (chloromethyl) pyridine and 2-hydroxy -? / - [(1 R) -2- (. {4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin-5-yl.} oxy) -1-methylethyl] -? / - methylacelamide to give the title compound as a white solid in 15% yield; NMR spectrum (DMSO-d6 373K) 1.25 (d, 3H), 2.28 (s, 3H), 2.83 (s, 3H), 3.96 (s, 2H), 4.35 (m, 1 H), 4.46 (t, 1 H), 4.97 (m, 1 H), 5.19 (s, 2H), 7.01 (d, 1 H), 7.18 (d, 2H), 7.33 (m, .2H), 7.44 (m, 1 H), 7.56 (d, 1 H), 7.68 (t, 1 H), 8.40 (s, 1 H), 8.58 (d, 1 H), 9.48 (s, 1 H); Mass Spectrum MH * 488. 2-hydroxy -? / - [(1 R) -2- (. {4 - [(4-hydroxy-3-methylphenyl) amino] quinazolin-5-yl.} Oxy) -1-methyl ethyl] -? / - methylacetamide used as starting material is prepared as follows: The procedure described in Example 94 (preparation of starting materials) is repeated using acetyl acetoxychloride and 2-methyl-4 - [(5- { [(2R) -2- (methylamino) propyl] oxy} quinazolin-4-yl) amino] phenol (obtained as described in Example 93, preparation of starting materials) to give 2-hydroxy -? - [(1 R) -2- ( { 4- [(4-hydroxy-3-methylphenyl) amino] quinazolin-5-yl}. Oxy) -1-methylethyl] -? / - methylacetamide with or orange foam in 75% production; NMR spectrum (DMSO-d6 373K) 1.25 (d, 3H), 2.17 (s, 3H), 2.83 (s, 3H), 3.97 (s, 2H), 4.33 (dd, 1H), 4.45 (t, 1H), 4.95 (m, 1H), 6.77 (d, 1H), 7.17 (d, 1H), 7.30 (m, 3H), 7.67 (i, 1H), 8.37 (s, 1H), 8.79 (s, 1H), 9.43 (s, 1H); Mass Spectrum MH * 397. Example 97 2-Hydroxy-V-methyl-W-. { (1R) -1-metiI-2 - [(4- {[3-methyl-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl } acetamide The procedure described in Example 3 is repeated using 4- (chloromethyl) -1,3-thiazole and 2-hydroxy-β / - [(1R) -2- (. {4 - [(4-hydroxy-3- methylphenyl) amino] quinazolin-5-yl.}. oxy) -1-methylethyl] -? / - mefilacetamide (obtained as described in Example 96, preparation of starting materials) to give the title compound as a foam on the basis of % production; NMR spectrum (DMSO-d6373K) 1.26 (d, 3H), 2.24 (s, 3H), 2.83 (s, 3H), 3.97 (s, 2H), 4.35 (m, 1H), 4.46 (s, 1H), 4.95 (m, 1H), 5.24 (s, 2H), 7.08 (d, 1H), 7.18 (d, 2H), 7.35 (d, 1H), 7.42 (s, 1H), 7.46 (d, 1H), 7.70 ( m, 1H), 8.41 (s, 1H), 9.07 (s, 1H), 9.50 (s, 1H); Mass Spectrum MH * 494. Example 98? V-. { (2R) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyI] amino} quinazolin-5-yl) oxy] propyl} -1-Hydroxy- / V-methylcyclopropanecarboxamide The procedure described in Example 1 is repeated by using hydroxy-1-cyclopropane carboxylic acid and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5 - [(1 R) -1-methyl- 2- (mephilamino) efoxy] quinazolin-4-amine (obtained as described in Example 2.3, preparation of initial materials) to give the compound of the product as a foam in 1% yield; NMR spectrum (DMSO-d6) 0.70 (s, 4H), 1.40 (d, 3H), 3.23 (s, 3H), 3.36 (m, 1 H), 4.19 (m, 1 H), 5.15 (m, 1 H), 5.29 (s, 2H), 6.20 (s, 1 H), 7.24 (m, 2H), 7.35 (m, 2H), 7.58 (m, 2H), 7.71 (t, 1 H), 7.87 ( dt, 1 H), 8.09 (d, 1 H), 8.44 (s, 1 H), 8.58 (d, 1 H), 9.86 (s, 1 H); Mass Spectrum MH * 534. Example 99 (2S) -W-. { (2R) -2 - [(4- {[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazoln-5-yl) oxy] propyl} -2-hydroxy- / V-methylpropanamide The procedure described in Example 1 was repeated using L - (+) - lactic acid and? / - [3-cyoro-4- (pyridin-2-ylmethoxy) phenyl] -5- [(1R) -1-methyl-2- (methylamino) ethoxy] quinazolin-4-amine (obtained as described in Example 2.3, preparation of starting materials) to give the title compound as a white solid in 35% yield; NMR spectrum (DMSO-d6 373K) 1.07 (d, 3H), 1.45 (d, 3H), 2.98 (s, 3H), 3.22 (m, 1H), 4.19 (m, 1H), 4.43 (m, 1H), 5.15 (m, 1H), 5.27 (s, 2H), 7.22 (m, 2H), 7.35 (m, 2H), 7.59 (m, 2H), 7.69 (t, 1H), 7.84 (dt, 1H), 8.08 (d, 1H), 8.47 (s, 1H), 8.58 (d, 1H), 9.93 (s, 1H); Mass Spectrum MH + 522. Example 100 W-. { (2R) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyI] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxy- / V, 2-dimethylpropanamide The procedure described in Example 1 is repeated by using 2-hydroxy-iso-butyric acid and? / - [3-chloro-4- (pyridin-2-ylmehoxy) phenyl] -5 - [(1R) -1-methyl- 2- (meitylamino) efoxy] quinazolin-4-amine (obtained as described in Example 2.3, preparation of starting materials) to give the title compound as a white solid in 28% yield; NMR spectrum (DMSO-d6 373K) 1.25 (s, 3H), 1.27 (s, 3H), 1.43 (d, 3H), 3.26 (s, 3H), 3.54 (m, 1H), 4.16 (dd, 1H), 5.16 (m, 1H), 5.28 (s, 2H), 7.23 (m, 2H), 7.34 (m, 2H), 7.58 (m, 7.69 (t, 1H), 7.83 (di, 1H), 8.07 (d, 1H), 8.46 (s, 1H), 8.58 (d, 1H), 9.88 (s, 1H), Mass Spectrum MH * 536. Example 101 (2R) -? V- { (2R) -2- [ (4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxy-V-methylpropanamide The procedure described in Example 1 is repeated using D - (-) lactic acid and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5 - [(1R) -1-methyl-2 - (methylamino) ethoxy] quinazolin-4-amine (obtained as described in Example 2.3, preparation of starting materials) to give the title compound as a white solid in 26% yield; NMR spectrum (DMSO-d6 373K) 1.15 (d, 3H), 1.44 (d, 3H), 2.97 (s, 3H), 3.16 (m, 1H), 4.05 (dd, 1H), 4.43 (m, 1H), 5.16 (m, 1H), 5.27 (s, 2H), 7.23 (m, 2H), 7.35 (m, 2H), 7.59 (m, 2H), 7.70 (t, 1H), 7.84 (dt, 1H), 8.09 (d, 1H), 8.47 (s, 1H), 8.59 (d, 1H), 9.90 (s, 1 HOUR); Mass Spectrum MH * 522. Example 102 (2R) -W-. { (2R) -2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-methoxy-? R-meti I pro pan amide The procedure described in Example 1 is repeated using (R) - (+) - 2-methoxypropionic acid and? / - [3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] -5 - [(1R) - 1-mephyl-2- (methylamino) ethoxy] quinazolin-4-amine (obtained as described in Example 2.3, preparation of starting materials) to give the title compound as a brown gum in 44% yield; NMR spectrum (DMSO-d6373K) 1.11 (d, 3H), 1.37 (d, 3H), 2.97 (s, 3H), 3.09 (s, 3H), 3.38 (m, 1H), 4.17 (q, 1H), 4.26 (dd, 1H), 5.16 (m, 1H), 5.28 (s, 2H), 7.24 (m, 2H), 7.33 (d, 1H), 7.37 (dd, 1H), 7.56 (d, 1H), 7.64 (d, dd, 1H), 7.69 (t, 1H), 7.86 (di, 1H), 8.13 (d, 1H), 8.44 (s, 1H), 8.59 (d, 1H), 9.89 (s, 1H); Mass Spectrum MH * 536. Example 103 2-Hydroxy-W-methyl-N - ((2R) -2- { [4 - ([3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl.}. amino) quinazolin-5-yl] oxy}. propyl) acetamide The procedure described in Example 1 is repeated using glycolic acid and 5 - [(1 R) -1-methyl-2- (methylamino) eioxy] -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine to give the title compound in 86% yield; NMR spectrum (CDCI3) 1 .55 (d, 3H), 2.30 (s, 3H), 2.53 (s, 3H), 2.96 (s, 3H), 3.59 (dd, 1 H), 4.16-4.07 (m, 3H) ), 5.08 (m, 1 H), 6.92 (d, 1 H), 7.02 (d, 1 H), 7.09 (d, 1 H), 7.14 (d, 1 H), 7.50 (m, 2 H), 7.65 (m, 2H), 8.28 (s, 1 H), 8.61 (s, 1 H), 9.87 (s 1 H); Mass Spec. MH * 488. 5 - [(1 R) -1-methyl-2- (methylamino) ethoxy] -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazoline-4-amine used as starting material is prepared as follows: Sodium hydride (25.6 g, 60% dispersion in oil, 0.64 mol) is added per portion to a solution of 5-hydroxy-2-methylpyridine (70 g , 0.64 mol) in DMA (700 ml) while maintaining the temperature below 40 ° C. At the end of the addition, the mixture is stirred at room temperature for 1 hour and 2-fluoro-5-nitrotoluene (91.3 g, 0.59 mol) in DMA (100 ml) is added slowly. The mixture is stirred at 80 ° C for 3 hours and then cooled. The solvents are evaporated under vacuum and the residue is partitioned between ethyl acetate and water. The organic layer is rinsed with water and brine, dried over MgSO4.

After evaporation of the solvents, the residue is purified by chromatography on silica gel (eluent: 30% ethyl acetate in petroleum ether) to give 2-methyl-5- (2-meityl-4-niiro-phenoxy) pyridine ( 141 g, 98%) as an oil; NMR spectrum (CDCI3); 2.43 (s, 3H), 2.59 (s, 3H), 6.74 (d, 1 H), 7.21 (d, 1 H), 7.27 (d, 1 H), 8.00 (d, 1 H), 8.17 (s, 1 H), 8.32 (s, 1 H). A mixture of 2-meityl-5- (2-methyl-4-nitrophenoxy) pyridine (141 g, 0.58 mol) and 1.0% palladium in charcoal (13 g) in ethyl acetate (200 ml) and ethanol (700 g) ml) is stirred under a hydrogen atmosphere (1.2 bar) for 5 hours. After finishing the reaction, the mixture is purged with nitrogen and the catalyst is filtered. The filtrate was evaporated to dry to give 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] aniline (120.6 g, 98%) as a white solid.; Mass Spec. MH * 215. 3-Meiyl-4 - [(6-methylpyridin-3-yl) oxy] aniline (6.42 g, 30 mmol) and 4 N hydrogen chloride in dioxane (7.55 mL, 30 mmol) were added. add to a suspension of 4-chloro-5-fluoroquinazoline (5 g, 27.5 mmol, obtained as described in Sol. Int. PCT WO2001094341, AstraZeneca) in acetonifril (100 ml). The mixture is stirred at 80 ° C for 2 hours. After cooling, the precipitate is rinsed with acetoniiril. This precipitate is divided between DCM and 5% aqueous sodium bicarbonate and the pH is adjusted to 8. The organic layer is rinsed with brine and dried over MgSO 4. The evaporation of the solvents gives 5-fluoro -? / -. { 3-methyl-4 - [(6-metipyridin-3-yl) oxy] phenyl} quinazolin-4-amine (9.3 g, 94%) as a dark gum that crystallizes permanently; Spectrum NM R (CDCl 3); 2.30 (s, 3H), 2.54 (s, 3H), 6.93 (d, 1 H), 7.15-7.08 (m, 2H), 7.22 (m, 1 H), 7.56 (d, 1 H), 7.63 (s) , 1 H), 7.71 (m, 2 H), 8.27 (s, 1 H), 8.37 (d, 1 H), 8.71 (s, 1 H). Sodium hydride (960 mg, 60% dispersion in oil, 20 mmol) is added per portion to a cold solution of (2R) -1 - [allyl (mephyl) amino] propan-2-ol (3.87 g, 30 mmol, obtained as described in Example 2.3, preparation of starting materials) and 5-fluoro-? / -. { 3-mephyl-4 - [(6-meilypyridin-3-yl) oxy] phenyl} Chenazol-4-amine (3.6 g, 10 mmol) in THF (25 ml). The mixture is heated at 65 ° C for 24 hours. After cooling, the solvents are evaporated under vacuum. The mixture is diluted with DCM, and rinsed with water and brine. The organic layer is dried over MgSO4. After evaporation of the solvents, the residue is purified by chromatography on silica gel (eluent: 2 to 4% methanol in DCM) to give 5-. { (1 R) -2- [allyl (methyl) ami n o-1-m eti-letoxy} -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine (2.4 g, 51%) as a brown oil; Mass Spectrum: MH * 470. A mixture of 5-. { (1 R) -2- [allyl (methyl) amino-1-methylethoxy} -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine (2.25 g, 4.8 mmol) and chlorotris (triphenylphosphine) rhodium (1) (463 mg, 0.48 ml) in acefonitrile-water (17 ml: 3 ml) is heated at reflux for 3 hours. After cooling, the solvents are evaporated under vacuum. The residue is purified by chromatography on silica gel (eluent: 2 to 4% methanol in DCM) to give 5 - [(1 R) -1-methyl-2- (methylamino) ethoxy] -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine (1.70 g, 83%); Spectrum of Mass MH * 430. Example 104? F-Methyl- / V - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl.}. amino) quinazolin-5-yl] oxy}. propyl) acetamide Acetyl chloride (24 μl, 0.33 mmol) is added dropwise to a solution of 5 - [(1 R) -1-methyl-2- (mephilamino) eioxy] -? / -. { 3-meityl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazole-4-amine (129 mg, 0.30 mmol, obtained as described in Example 103, preparation of starting materials) and DI PEA (1 05 μL, 0.6 mmol) in DCM (5 mL). The mixture is stirred at room temperature for 2 hours and diluted with DCM. The solution is rinsed with water and brine, and dried over MgSO 4. After evaporation of the solvents, the residue is purified by chromatography on silica gel (eluent: 2 to 4% methanol in DCM) to give the title compound (84 mg, 60%) as a pale solid; NMR spectrum (CDCI3) 1 .55 (d, 3H), 2.08 (s, 3H), 2.30 (s, 3H), 2.53 (s, 3H), 3.08 (s, 3H), 3.56 (dd, 1 H), 3.93 (dd, 1 H), 5.09 (, 1 H), 6.92 (d, 1 H), 7.12 (m, 3 H), 7.50 (m, 2 H), 7.65 (m, 1 H), 7.70 (s, 1 H), 8.27 (s, 1 H), 8.62 (s, 1 H); Species of Mass: MH * 472. Example 105? Íí. v2, yV2-Trimethyl-N1 - ((2R) -2- { [4- ( {3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyI}. amino) quinazoline -5-yl] oxy}. Propyl) glycinamide Acetyl chlorochloride (33 μl, 0.42 mmol) is added dropwise to a solution of 5 - [(1 R) -1-methyl-2- (methylamino) etoxi] -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine (172 mg, 0.40 mmol, obtained as described in Example 103, preparation of starting materials)) and DIPEA (139 μL, 0.8 mmol) in DCM (2 mL). The mixture is stirred at ambient temperature for 1 hour. THF (5 ml) is added to the solution and dimethylamine is bubbled into the reaction mixture. After 30 minutes, the solvents are evaporated under vacuum. The mixture is diluted with DCM, rinsed with water and brine, and dried over MgSO4. After evaporation of the solvents, the residue is purified by chromatography on silica gel (elute: 2 to 4% 7N ammonium-methanol in DCM) to give the title compound (85 mg, 41%) as a pale solid; NMR spectrum (CDCI3) 1 .53 (d, 3H), 2.28 (s, 6H), 2.30 (s, 3H), 2.53 (s, 3H), 3.1 5-3.05 (m, 5H), 3.54 (dd, 1 H), 3.95 (dd, 1 H), 5.10 (m, 1 H), 6.91 (d, 1 H), 7.12 (m, 3H), 7.46 (d, 7.55 (d, 1 H), 7.64 (m, 1 H), 7.72 (s, 1 H), 8.27 (s, 1 H), 8.62 (s, 1 H); Mass Spectrum MH * 51 5. Example 106 V-methyl-W - ((2R) -2 - { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) q uinzolin-5-yl] oxy} propi) -2-pyrrolidin-1-ylacetamide The procedure described in Example 105 is repeated using pyrrolidine (4 equivalents) in place of dimethylamine to give the thixture compound in 57% yield; NMR spectrum (CDCI3) 1.53 (d, 3H), 1.75 (m, 4H), 2.30 (s, 3H), 2.55 (m, 7H), 3.13 (s, 3H), 3.27 (d, 1H), 3.32 (d , 1H), 3.57 (dd, 1H), 3.92 (dd, 1H), 5.11 (m, 1H), 6.91 (d, 1H), 7.12 (m, 3H), 7.46 (d, 1H), 7.54 (d, 1H), 7.64 (m, 1H), 7.72 (s, 1H), 8.27 (s, 1H), 8.62 (s, 1H); Mass Spectrum MH * 541. EXAMPLE 107 V-Methyl-1 - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl.}. amino) quinazolin-5-yl] oxy}. propyl) -2-morpholin-4-ylacetamide The procedure described in Example 105 is repeated using morpholine (4 equivalents) in place of dimellylamine to give the title compound in 63% yield; NMR spectrum (CDCI3) 1. 53 (d, 3H), 2.30 (s, 3H), 2.48 (m, 4H), 2.53 (s, 3H), 3.15 (m, 5H), 3. 53 (dd, 1H), 3.65 (m, 4H), 3.97 (dd, 1H), 5.11 (m, 1H), 6.92 (d, 1H), 7. 14-7.07 (m, 3H), 7.46 (d, 1H), 7.54 (d, 1H), 7.63 (m, 1H), 7.72 (s, 1H), 8.27 (s, 1H), 8.62 (s, 1H), 9.93 (s, 1H); Mass Spectrum: MH * 557. Example 108 W-methyl-? V - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazolin-5-yl] oxy}. propyl) -2- (4-methylpiperazin-1-yl) acetamide The procedure described in Example 105 is repeated using? / - methylpiperazine (4 equivalents) in place of dimethylamine to give the title compound in 68% yield; NMR spectrum (CDCI3) 1.53 (d, 3H), 2.25 (s, 3H), 2.30 (s, 3H), 2.5-2.2 (m, 8H), 2.53 (s, 3H), 3.15 (m, 5H), 3.54 (dd, 1H), 3.94 (dd, 1H), 5.11 (m, 1H), 6.92 (d, 1H), 7.14-7.07 (m, 3H), 7.45 (d, 1H), 7.54 (d, 1H), 7.64 (m, 1H), 7.72 (s, 1H), 8.27 (s, 1H), 8.62 (s, 1H); Mass Spec. MH * 570. EXAMPLE 109 2-Hydroxy-V-methyl-V - ((2S) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3- il) oxy) phenyl.}. amino) quinazolin-5-yl] oxy}. propyl) acetamide The procedure described in Example 1 is repeated using glycolic acid and 5 - [(1 S) -1-methyl-2- (methylamino) ethoxy] -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine to give the title compound in 46% yield; NMR spectrum (CDCI3) 1 .55 (d, 3H), 2.30 (s, 3H), 2.53 (s, 3H), 2.96 (s, 3H), 3.59 (dd, 1 H), 4.16-4.07 (m, 3H) ), 5.08 (m, 1 H), 6.92 (d, 1 H), 7.02 (d, 1 H), 7.09 (d, 1 H), 7.14 (d, 1 H), 7.50 (m, 2 H), 7.65 (m, 2H), 8.28 (s, 1 H), 8.61 (s, 1 H), 9.87 (s 1 H): Mass Spec. MH * 488. 5 - [(1 S) -1 -methyl-2- (methylamino) ethoxy] -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine used as starting material is prepared as follows: The procedure described in Example 1 03, preparation of starting materials, is repeated using (2S) -1 - [allyl (methyl) amino] propan-2-ol ( obtained as described for the aníipode R in Example 2.3, preparation of initial materials) and 5-fluoro- / V-. { 3-methyI-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine (obtained as described in Example 103, preparation of starting materials) to give 5-. { (1 S) -2- [allyl (methyl) amino] -1-methyletoxyl} -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amino in 92% yield as a gum; Mass Spectrum MH * 470. The procedure described in Example 103, preparation of initial materials, is repeated using 5-. { (1 S) -2- [allyl (methyl) amino] -1-methylethoxy} -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine to give 5 - [(1 S) -1-methyl-2- (methylamino) -ioxy] -? / -. { 3-meityl-4 - [(6-meilypyridin-3-yl) oxy] phenyl} quinazolin-4-amine in 56% yield; Mass Spec. MH * 430. Example 1 10? F-ethyl-W - ((2S -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] ] phenyl.}. amino) quinazolin-5-yl] oxy}. propyl) acetamide The procedure described in Example 104 is repeated using 5 - [(1 S) -1-methyl-2- (methylamino) ethoxy] -? / -. { 3-Mephyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine (obtained as described in Example 1 09, preparation of starting materials) and acetic anhydride to give the title compound in 64% yield; NMR spectrum (CDCl3) 1.55 (d, 3H), 2.08 (s, 3H), 2.30 (s, 3H), 2.53 (s, 3H), 3.08 (s, 3H), 3.56 (dd, 1 H), 3.93 (dd, 1 H), 5.09 (m, 1 H), 6.92 (d, 1 H), 7.12 (m, 3 H), 7.50 (, 2 H), 7.65 (m, 1 H), 7.70 (s, 1 H), 8.27 (s, 1 H), 8.62 (s, 1 H); Mass Spectrum MH * 472. Example 1 1 1 W-ethyl-? Í - ((2S) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl ) oxy] phenyI.}. amino) quinazolin-5-yl] oxy}. propyl) -2-pyrrolidin-1-ylacetamide The procedure described in Example 105 is repeated using 5 - [(1S) -1-methyl-2- (meitylamino) eioxy] -? / -. { 3-meityl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine (obtained as described in Example 109, preparation of initial materials) and pyrrolidine (4 equivalents) in place of dimethylamine to give the title compound in 51% yield; NMR spectrum (CDCI3) 1.53 (d, 3H), 1.75 (m, 4H), 2.30 (s, 3H), 2.55 (m, 7H), 3.13 (s, 3H), 3.27 (d, 1H), 3.32 (d , 1H), 3.57 (dd, 1H), 3.92 (dd, 1H), 5.11 (m, 1H), 6.91 (d, 1H), 7.12 (m, 3H), 7.46 (d, 1H), 7.54 (d, 1H), 7.64 (m, 1H), 7.72 (s, 1H), 8.27 (s, 1H), 8.62 (s, 1H); Mass Spectrum MH * 541. Example 112 (2S) -2,4-Dihydroxy-? - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin -3-yl) oxy] phenyl.}. Amino) quinazolin-5-yl] oxy}. Propyl) butanamide 9 »H i f? The procedure described in Example 63 is repeated using 5 - [(1 R) -2-amino-1-methylefoxy] -? / -. { 3-meityl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine and (S) -a-hydroxybutyrolactone to give the title compound in 53% yield as a solid; NMR spectrum (CDCI3) 1.55 (d, 3H), 1.79 (m, 1 H), 2.05 (m, 1 H), 2.26 (s, 3H), 2.49 (s, 3H), 3.90-3.65 ( m, 4H), 4.21 (dd, 1 H), 4.94 (m, 1 H), 6.96 (m, 2H), 7.1 1 (d, 1 H), 7.23 (dd, 1 H), 7.39 (d, 1 H), 7.43 (m, 1 H), 7.60-7.52 (m, 2H), 7.69 (s, 1 H), 8.00 (s, 1 H), 8.55 (s, 1 H); Mass Spectrum MH * 518. 5 - [(1) -2-amino-1-methylethoxy] -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} The quinazolin-4-amine used as the starting material is prepared as follows: The procedure described in Example 103 (preparation of starting materials) is repeated using 5-fluoro-γ / -. { 3-methyl-4 - [(6-meilypyridin-3-yl) oxy] phenyl} quinazolin-4-amine (obtained as described in Example 103, preparation of starting materials) and (2R) -1-aminopropan-2-ol to give 5 - [(1 R) -2-amine-1-methylethoxy] -? / -. { 3-methyl-4 - [(6-mephylpyridin-3-yl) oxy] phenyl} quinazolin-4-amino in 77% production; Mass Spec. MH * 416 Example 113 (2S) -4-Bromo-2-hydroxy-N - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin -3-yl) oxy] phenyl.}. Amino) quinazoIin-5-yl] oxy}. Propyl) butanamide Triphenylphosphine (650 mg, 2.5 mmol) is added per portion for 30 minutes to a solution of (2S) -2,4-dihydroxy-N - ((2R) -2- { [4- (. {3- methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazolin-5-yl] oxy} propyl) buanamide (856 mg, 1.65 mmol, obtained as described in Example 1 12) and carbon tetrabromide (658 mg, 2 mmol) in DCM (10 mL). The mixture is stirred overnight at room temperature. After evaporation of the solvents, the residue is purified by chromatography on silica gel (eluent: 2% to 5% 7N ammonium-methanol in DCM) to give the title compound (712 mg, 74%) as a solid; NMR spectrum (CDCI3) 1 .53 (d, 3H), 2.07 (m, 1 H), 2.28 (s, 3H), 2.38 (m, 1 H), 2.52 (s, 3H), 3.51 (t, 2H) , 3.80-3.65 (m, 2H), 4.34 (dd, 1 H), 4.95 (m, 1 H), 6.90 (m, 2H), 7.09 (d, 1 H), 7.14 (dd, 1 H), 7.28 (m, 1 H), 7.50 (m, 3 H), 7.63 (s, 1 H), 8.23 (s, 1 H), 8.44 (s, 1 H); Mass Spectrum MH * 580, 582. Example 114 / V- (2-Chloroethyl) - / V, - ((2R) -2- { [4- (. {3-methyl-4 - [(6 -methylpyridin-3-M) oxy] phenyl.}. amino) quinazoIin-5-yl] oxy}. propyl) urea Chloroethylisocyanate (1 16 μl, 1.36 mmol) is added dropwise to a cold solution of 5 - [(1 R) -2-amino-1-methylethoxy] -? / -. { 3-meityl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine (516 mg, 1.24 mmol, obtained as described in Example 1 12, preparation of starting materials) in DCM (10 mL). The mixture is stirred at 0 ° C for 30 minutes and at room temperature for 1 hour. After evaporation of the solvents, the residue is purified by chromatography on silica gel (eluent: 3% to 5% 7N ammonium-methanol in DCM) to give the title compound (584 mg, 74%); NMR spectrum (CDCI3) 1 .46 (d, 3H), 2.28 (s, 3H), 2.52 (s, 3H), 3.46 (m, 1 H), 3.57 (m, 4H), 4.00 (m, 1 H) , 4.76 (m, 1 H), 6.40 (m, 1 H), 6.62 (m, 1 H), 6.67 (d, 1 H), 6.91 (d, 1 H), 7.08 (d, 1 H), 7.12 (dd, 1 H), 7.18 (d, 1 H), 7.34 (t, 1 H), 7.53 (dd, 1 H), 7.67 (s, 1 H), 8.27 (s, 1 H), 8.34 (s) , 1 H), 9.82 (s, 1 H); Mass Spectrum MH * 521. EXAMPLE 1 2-Hydroxy- / V-methyl-N - ((1 R) -1-methyl-2 { [4- (. {3-methyl-4- [ (6-methy1-pyridin-3-yl) oxy] phenyl} amino) quinazolin-5-yl] oxy} ethyl) acetamide Acetoxyacetyl chloride (70 μl, 0.64 mmol) was added to goya to a cold solution of 5-. { [(2R) -2- (methylamino) propyl] oxy} -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine (250 mg, 0.58 mmol), triethylamine (97 μl, 0.70 mmol) in DCM (7 ml). The mixture is warmed to room temperature and stirred for 2 hours. After evaporation of the solvents under vacuum, the residue is diluted with pyrrolidine (0.50 ml, 6 mmol) and the mixture is stirred at 65 ° C for 2 hours. After evaporation of the mixture to dryness, the residue is injected onto a HPLC column (C1 8, 5 microns, diameter of 1 9 mm, length 100 mm) of a preparative HPLC-MS system eluting with a water mixture ( containing 5% methanol and 1% acetic acid) and acetonitrile (gradient). After evaporation of the solvents, the solid is diluted in DCM. The solution is rinsed with aqueous sodium bicarbonate and dried over magnesium sulfate to give the title compound (140 mg, 49%); NMR spectrum (CDCI3) 1 .34 (d, 3H), 2.30 (s, 3H), 2.53 (s, 3H), 2.79 (s, 3H), 3.12 (m, 1 H), 3.95 (dd, 1 H) , 4.09 (dd, 1 H), 4.30-4. 1 5 (m, 2H), 5.40 (m, 1 H), 6.91 (m, 2H), 7.09 (d, 1 H), 7.17 (dd, 1 H), 7.38 (m, 1 H), 7.46 (s) , 1 H), 7.50 (d, 1 H), 7.64 (t, 1 H), 8.30 (d, 1 H), 8.58 (s, 1 H), 9.36 (s, 1 H); Specter of Mass MH * 488. 5-. { [(2R) -2- (meitylamino) propyl] oxy} - / V-. { 3-meityl-4 - [(6-meilypyridin-3-yl) oxy] phenyl} The quinazolin-4-amine used as starting material is prepared as follows: The procedure described in Example 103, preparation of starting materials, is repeated using 5-fluoro-? -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine (obtained as described in Example 1 03, preparation of initial materials) and (2R) -2- (methylamino) propan-1 -ol (obtained as described in Becker et al., J. Chem Soc. 1957, 858) to give 5-. { [(2R) -2- (methylamino) propyl] oxy} -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine in 75% yield; NMR spectrum (CDCI3) 1 .30 (d, 3H), 2.28 (s, 3H), 2.52 (s, 3H), 2.53 (s, 3H), 3.20 (m, 1 H), 4.09 (m, 1 H) , 4.21 (m, 1 H), 6.89 (m, 2H), 7.14-7.07 (m, 2H), 7.45 (d, 1 H), 7.63 (m, 2H), 8.26 (s, 1 H), 8.63 ( s, 1 H), 10.3 (bs, 1 H); Mass Spec. MH * 430. Example 1 16 N-ethyl-N - ((1 R) -1-methyl-2 { [4- (. {3-methyl-4 - [(6-methylpyridin- 3-yl) oxy] phenyl.}. Amino) quinazolin-5-yl] oxy} ethyl) acetamide Acetic anhydride (66 μl, 0.70 mmol) is added dropwise to a solution of 5-. { [(2R) -2- (methylamino) propyl] oxy} -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine (250 mg, 0.58 mmol, obtained as described in Example 1, preparation of starting materials) and potassium carbonate (161 mg, 1.16 mmol) in aceine (10 ml). The mixture is stirred at ambient temperature for 2 hours. After evaporation of the solvents, the residue is diluted in DCM. The solution is rinsed with aqueous sodium bicarbonate and dried over magnesium sulfate. After evaporation of the solvents, the residue is purified by chromatography on silica gel (eluent: 2 to 5% 7N ammonium-methanol in DCM) to give the title compound (230 mg, 84%); Specimen NMR (CDCI3) 1 .28 (d, 3H), 1.94 (s, 3H), 2.30 (s, 3H), 2.53 (s, 3H), 2.90 (s, 3H), 4.30-4.10 (m, 2H), 5.38 (m, 1 H), 6.92 (m, 2H), 7.08 (d, 1 H), 7.14 (dd, 1 H), 7.48 (d, 2H), 7.53 (s, 1 H), 7.64 (f, 1 H), 8.27 (d, 1 H), 8.60 (s, 1 H), 9.51 (s, 1 H); Specter of Mass MH * 472.

Example 117 2-Hydroxy-V-methyl-W - ((1S) -1-methyl-2- { [4- (. {3-methyl-4 - [(6-methylpyridin-3-yl) oxy] ] phenyl} amino) quinazolin-5-yl] oxy} ethyl) acetamide The procedure described in Example 115 is repeated using 5-. { [(2S) -2- (methylamino) propyl] oxy} -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine to give the title compound in 72% yield; NMR spectrum (CDCI3) 1.34 (d, 3H), 2.30 (s, 3H), 2.53 (s, 3H), 2.79 (s, 3H), 3.12 (m, 1H), 3.95 (dd, 1H), 4.09 (dd) , 1H), 4.30-4.15 (m, 2H), 5.40 (m, 1H), 6.91 (m, 2H), 7.09 (d, 1H), 7.17 (dd, 1H), 7.38 (m, 1H), 7.46 ( s, 1H), 7.50 (d, 1H), 7.64 (t, 1H), 8.30 (d, 1H), 8.58 (s, 1H), 9.36 (s, 1H); Mass Spectrum MH * 488. 5-. { [(2S) -2- (methylamino) propyl] oxy} -? / -. { 3-meityl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine used as starting material is prepared as follows: The procedure described in Example 103, preparation of starting materials, is repeated using 5-fluoro-? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine (obtained as described in Example 103, preparation of starting materials) and (2S) -2- (methylamino) propan-1-ol (obtained as described in Chacchio et al., Tetrahedron, 1995, 51, 5689) to give 5-. { [(2S) -2- (methylamino) propyl] oxy} -? / -. { 3-methyl-4 - [(6-methy1-pyridin-3-yl) oxy] phenyl} quinazolin-4-amine in 71% yield; NMR spectrum (CDCI3) 1.30 (d, 3H), 2.28 (s, 3H), 2.52 (s, 3H), 2.53 (s, 3H), 3.20 (m, 1H), 4.09 (m, 1H), 4.21 (m , 1H), 6.89 (m, 2H), 7.14-7.07 (m, 2H), 7.45 (d, 1H), 7.63 (m, 2H), 8.26 (s, 1H), 8.63 (s, 1H); Mass Spectrum MH * 430. EXAMPLE 118 W-Methyl-iV - ((1S) -1-methyl-2- { [4- (. {3-methyl-4 - [(6-methylpyridin-3-) il) oxy] phenyl.}. amino) qu? nazolin-5-yl] oxy} ethyl) acetamide; The procedure described in Example 116 is repeated using 5-. { [(2S) -2- (methylamino) propyl] oxy} -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine (obtained as described in Example 117, preparation of starting materials) and acetic anhydride to give the title compound in 88% yield; NMR spectrum (CDCI3) 1-28 (d, 3H), 1.94 (s, 3H), 2.30 (s, 3H), 2.53 (s, 3H), 2.90 (s, 3H), 4.30-4.10 (m, 2H) , 5.38 (m, 1H), 6.92 (m, 2H), 7.08 (d, 1H), 7.14 (dd, 1H), 7.48 (d, 2H), 7.53 (s, 1H), 7.64 (t, 1H), 8.27 (d, 1H), 8.60 (s, 1H), 9.51 (s, 1H); Mass Spectrum MH * 472. Example 119 Methyl-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} methylcarbamate; ? / - [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (methylamino) ethoxy] quinazolin-4-amine (obtained as described in Example 1, preparation of starting materials, 217 mg) and DIPEA (0.2 ml) were stirred in DCM (20 ml). Chloroformate of meily (0.043 ml) is added slowly and the resulting solution is stirred for 1 8 hours. The solution is evaporated and the residue is purified by chromatography, eluting with increasing concentrations of methanol in ethyl acetate (5-10%). The appropriate fractions are evaporated to an oil, which is triturated with acetonitrile to give the compound of the product as a solid (43 mg, 17%); NMR spectrum (DMSO-d6 @ 373K) 2.88 (s, 3H), 3.30 (s, 3H), 3.75-3.85 (t, 2H), 4.35-4.55 (bs, 2H), 5.30 (s, 2H), 7.10- 7.30 (m, 2H), 7.30-7.40 (m, 2H), 7.50-7.60 (m, 2H), 7.70-7.78 (t, 1 H), 7.80-7.95 (m, 2H), 8.43 (bs, 1 H) ), 8.75-8.80 (d, 1 H), 9.60-9.80 (bs, 1 H); Mass Spec. MH * 494.0 Example 120 V-. { 2 - [(4- {[[3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} - /, / '- dimethylurea Methyl isocyanate (0.035 ml) is added slowly to a stirred solution of? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (methylamino) ethoxy] quinazolin-4-amine (obtained as described in Example 1, preparation of starting materials, 217 mg) in DCM (10 ml). The resulting solution is stirred for 2 hours and then evaporated. The residue is triturated with acetonitrile and the resulting solid is rinsed with ether to give the title compound as a solid (205 mg, 83%); NMR spectrum (DMSO-d6 @ 373K) 2.85 (s, 3H), 2.95 (s, 3H), 3.75-3.85 (t, 2H), 4.35-4.45 (f, 2H), 5.25 (s, 2H), 5.90- 6.00 (bs, 1 H), 7.1 0-7.15 (d, 1 H), 7.15-7.25 (d, 1 H), 7.30-7.37 (i, 2H), 7.52-7.60 (m, 2H), 7.65-7.73 (t, 1 H), 7.80-7.86 (m, 1 H), 7.94-7.99 (d, 1 H), 8.44 (s, H), 8.55-8.60 (d, 1 H), 9.80 (s, 1 H) ); Mass Spectrum MH * 493.4. Example 121 T- (2-Chloroethyl) - / V-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - methylurea The procedure described in Example 120 is repeated using 2-chloroaryl isocyanate and? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5- [2- (methylamino) ethoxy] quinazolin-4- amine (obtained as described in Example 1, preparation of starting materials) to give the title compound as a solid in 80% yield; NMR spectrum (DMSO-d6 @ 373K) 2.90 (s, 3H), 3.1 5-3.25 (q, 2H), 3.43-3.50 (t, 2H), 3.75-3.85 (t, 2H), 4.35-4.45 (t, 2H), 5.25, 6.35 (bs, 1H), 7.08-7.13 (d, 1H), 7.13-7.30 (m, 1H), 7.35-7.40 (m, 2H), 7. 50-7.65 (m, 2H), 7.65-7.80 (m, 1H), 7.80-7.90 (t, 1H), 7.95 (d, 1H), 8. 50 (s, 1H), 8.55-8.60 (d, 1H), 9.80 (s, 1H); Mass specifier MH * 541. 3. Example 122 W-. { (2R) -2 - [(4- {[3-C? -orth-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazoIin-5-yl) oxy] propyl} - / V'-methylurea The procedure described in Example 120 is repeated using methylene isocyanate and 5 - [(1R) -2-amino-1-methylethoxy] -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl ] quinazolin-4-amine (obtained as described in Example 65, preparation of starting materials) to give the thiful compound as a solid in 43% yield; Specimen NMR (DMSO-d6 @ 373K) 1.40-1.45 (d, 3H), 2.50-2.55 (d, 3H), 3.38-3.48 (m, 1H), 3.50-3.60 (m, 1H), 4.83-4.92 (m , 1H), 5.28 (s, 2H), 5.55-5.65 (bs, 1H), 6.00-6.10 (bs, 1H), 7.19-7.24 (dd, 7.31-7.37 (m, 2H), 7.56-7.62 (m, 2H), 7.66-7.73 (í, 1H), 7.81-7.88 (dt, 1H), 8.06-8.08 (d, 1H), 8.48 (s, 1H), 8.55-8.60 (d, 1H), 9.95-10.05 ( bs, 1H): Mass Spectrum MH * 493.4 Example 123 Acid [((R) -2-. {4- [3-Chloro-4- (pyridin-2-ylmethoxy) phenylamino] quinazolin-5-yloxy} propylcarbamoyl) methyl) methylcarbamic tert-butyl ester - [(1 R) -2-amino-1-methyleneoxy] -? / - [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] quinazolin-4-amine (obtained as described in Example 65 , preparation of starting materials, 868 mg) is stirred in DCM (40 ml) with DI PEA (1 ml). ? / - (tert-bufoxicarbonyl) sarcosine (400 mg) and HATU (800 mg) are added and the mixture is stirred for 18 hours. Volatile material is removed by evaporation and the residue is purified by chromatography, eluting with increasing concentrations of mephanol in ethyl acetate (0-1 0%). Evaporation of the appropriate fractions gives the title compound as a foam (0.50 g); NMR spectrum (DMSO-d6 @ 373k) 1 .10 (s, 6H), 1 .20 (s, 3H), 1 .40-1.42 (d, 3), 2.72 (s, 3H), 3.40-3.60 (d , 1 H), (hidden by H2O), 3.60-3.75 (q, 2H), 3.75-3.80 (d, 1 H), 4.90-5.00 (bs, 1 H), 5.30 (s, 2H), 7.28-7.34 (q, 2H), 7.34-7.40 (m, 1 H), 7.42-7.46 (d, 1 H), 7.50-7.62 (m, 2H), 7.85-7.91 (dt, 1 H), 7.91 -7.99 (m , 2H), 8.24-8.34 (bs, 1 H), 8.57-8.62 (d, 1 H), 8.75 (s, 1 H), 1 0.60-10.70 (bs, 1 H); Mass Spectrum MH * 607. Example 124? / 1-. { (2R) -2- (4- { [3-Chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinozolin-5-yl) oxy] propyl} -N2-Methylene Glycinamide [((R) -2- (4- [3-Chloro-4- (pyridin-2-ylmethoxy) phenylamino] quinazolin-5-yloxy}]] propylcarbamoyl) methyl] methylcarbamate terry butyl ester (obtained as described in Example 123, 0.50 g) is stirred in trifluoroacetic acid (5 ml) for 20 hours, volatile material is removed by evaporation and the residue is purified by chromatography, eluting with aqueous ammonium (0.880), methanol, DCM (1: 10:90) Evaporation of the appropriate fractions gives the title compound as a solid (60 mg, 15%); (DMSO-d6 @ 373k) 1 .47-1 .50 (d, 3H), 2.20 (s, 3H), 3.10 (s, 2H), 3.45-3.55 (q, 1 H), 3.55-3.65 (q, 1 H), 4.85-5.00 (m, 1 H), 5.25 (s, 2H), 7.15-7.25 (q, 2H), 7.25-7.30 (m, 2H), 7.55-7.65 (t, 1 H), 7.70 -7.80 (m, 2H), 8.20 (s, 1 H), 8.50 (s, 1 H), 8.55-8.60 (d, 1 H), 9.85-9.95 (bs, 1 H); Mass Spectrum MH * 507. EXAMPLE 125 2-Hydroxy-W-methyl-W- (2- {[[4- ( {3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazoline -5-yl] oxy} ethyl) acetamide - [2- (Methylamino) ethoxy] -? / -. { 3-methyl-4 - [(6-methyl-pyridin-3-yl) oxy] phenyl} quinazolin-4-amine (32 mg, 0.077 mmol) and glycolic acid (6 mg, 0.085 mmol) are dissolved in DMA (10 ml). HATU (32 mg, 0.085 mmol) is added, and the mixture is stirred at room temperature for 16 hours. The mixture is concentrated in vacuo, and the residue is purified by reverse phase HPLC, eluting with 5 to 50% acetonitrile in H2O containing 0.2% TFA. The appropriate fraction is evaporated, and the residue is dissolved in methanol / DCM (1: 1, 25 ml). The mixture is neutralized by stirring overnight with feralkalkyl ammonium carbonate, bound polymer. The mixture is filtered, and the filtrate is evaporated. Crystallization from ethyl acetate // so-hexane gave 2-hydroxy-W-methyl -? / - (2 { [4- (. {3-methyl-4 - [(6-methylpyridin-3-yl) ) oxy] phenyl} amino) quinazolin-5-yl] oxy} ethyl) acetamide as a white crystalline solid (22 mg, 60%); NMR spectrum (DMSO-d6, 400 MHz, 373K) 2.26 (s, 3H), 2.48 (s, 3H), 3.02 (s, 3H), 3.95 (t, 2H), 4.02-4.1 1 (m-3H), 4.55 (t, 2H), 6.96 (d, 1 H), 7.20 (d, 1 H), 7.23 (m, 2H), 7 38 (d, 1 H), 7.65 (dd, 1 H), 7.70 (d , 1 H), 7.73 (dd, 1 H), 8.20 (m, 1 H), 8.49 (s, 1 H), 9.77 (s, 1 H); Mass Spectrum MH * 473.9. 5- [2- (methylamino) ethoxy] -? / -. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine used as starting material is prepared as follows: Sodium hydride (60% dispersion in mineral oil, 28 mg, 0.69 mmol) is suspended in DMA (10 ml) and? / - methylethanolamine (56 μl, 0.69 mmol) is added under a nitrogen atmosphere. The mixture is stirred for 20 minutes at room temperature, and 5-fluoro-V-. { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} quinazolin-4-amine (obtained as described in Example 103, preparation of starting materials, 100 mg, 0.28 mmol) is added. The mixture is heated under a nitrogen atmosphere at 1 1 0 ° C for 1 hour, then at 125 ° C for 14 hours. The mixture is cooled to room temperature, and acidified with TFA. The mixture is concentrated in vacuo, and the residue is purified by reverse phase HPLC eluting with 5 to 50% acetonifrile in H2O. The appropriate fractions are evaporated to a volume such that all the acetonitrile has been removed. The resulting aqueous solution is basified with concentrated aqueous ammonia, and extracted with DCM (4 x 20 ml). The combined extracts are filtered through a silicone-trapped filter paper and concentrated in vacuo to give 5- [2- (mephilamino) efoxy] -? / -. { 3-meityl-4 - [(6-meilypyridin-3-yl) oxy] phenyl} quinazolin-4-amine as a yellow solid (40 mg, 34%); NMR spectrum (CDCI3, 400 MHz) 2.20 (s, 3H), 2.44 (s, 3H), 2.49 (s, 3H), 3.12 (t, 2H), 4.25 (t, 2H), 6.80 (d, 1 H) , 6.83 (d, 1 H), 7.00 (d, 1 H), 7.04 (dd, 1 H), 7.39 (d, 1 H), 7.55 (dd, 1 H), 7.61 (dd, 1 H), 7.68 (d, 1 H), 8.19 (d, 1 H), 8.56 (s, 1 H), 10.26 (s, 1 H); Mass Spectrum MH * 416.0 Example 126 W-Methyl-W- (2- {[[4- ( {3-methyI-4 - [(6-methylpyridin-3-yl) oxy] phenyl}. ) quinazolin-5-yl] oxy} ethyl) acetamide ? / -. { 2 - [(4-Chloroquinazolin-5-yl) oxy] ethyl} -? / - methylacetamide (38 mg, 0.136 mmol) and 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] aniline (obtained as described in Example 103, preparation of starting materials, 32 mg, 0.150 mmol) are dissolved in / 'so-propanol, and the mixture is heated at reflux for 1 hour. The mixture is concentrated in vacuo and the residue is purified by chromatography, eluting with 0 to 5.5% (10: 1 methanol / NH3 (aC) conc.). Evaporation of the appropriate fractions da? / -methyl-? / - (2- {[[4- ( {3-meityl-4 - [(6-methylpyridin-3-yl) oxy] phenyl}. ) quinazolin-5-yl] oxy} ethyl) acetamide as a dry film (24 mg, 39%); NMR spectrum (DMSO-d6, 400 MHz), 373K 1.96 (s, 3H), 2.24 (s, 3H), 2.46 (s, 3H), 2.94 (s, 3H), 3.90 (t, 2H), 4.50 (t, 3H), 6.94 (d, 1 H), 7.18 (d, 1 H), 7.21 (m, 2H), 7.36 (d, 1 H), 7.63 (dd, 1 H), 7.68 (d, 1 H), 7.71 (dd, 1 H), 8.17 (dd, 1 H), 8.47 (s, 1 H), 9.76 (s, 1 H); Mass Spectrum MH * 458.4. ? / -. { 2 - [(4-chloroquinazolin-5-yl) oxy] ethyl} -? / - Methalostamide used as starting material is prepared as follows: Sodium hydride (60% dispersion in mineral oil, 732 mg, 18.3 mmol) is suspended in DMA (50 ml) and? / - methylethanolamine (734 μl, 9.1 5 mmol) is added under a nitrogen atmosphere. The mixture is stirred for 30 minutes at room temperature, and 5- fluoroquinazolin-4 (3H) -one (1.0 g, 6.10 mmol) is added. The mixture is heated under a nitrogen atmosphere at 85 ° C for 90 minutes. The mixture is cooled to room temperature, and the resulting paste is poured into methanol (100 ml). Dowex resin (50WX4-400, 25g) is added, and the mixture is stirred for 1 hour at room temperature. The resin is collected by filtration, and rinsed with meianol (100 ml). The resin is suspended in an ammonium solution in meianol (2.3 N, 150 ml), and the mixture is stirred for 30 minutes. The mixture is filtered and the residue is rinsed with ammonium in methanol (2.3 N, 100 ml). The combined filtrates are concentrated in vacuo, and dried in vacuo (1 mbar, 60 ° C) for 16 hours to give 5- [2- (methylamino) ethoxy] quinazolin-4 (3H) -one as off-white solid (1.09). g, 82%); NMR spectrum (DMSO-d6, 400 MHz) 2.36 (s, 3H), 2.85 (t, 2H), 5.1 1 (í, 2H), 6.97 (d, 1 H), 7.14 (d, 1 H), 7.61 ( dd, 1 H), 7.97 (s, 1 H); Mass Spec. MH * 220. 5- [2- (Methylamino) ethoxy] quinazolin-4 (3H) -one (823 mg, 3.76 mmol) is dissolved in pyridine (25 mL), and the solution is cooled to 0 ° C. . Anhydric acetic acid (1.20 ml, 12.70 mmol) is added dropwise; The solution is heated to room temperature and stirred for 90 minutes. The mixture is concentrated in vacuo, and the residue is purified by chromatography, eluting with 4% to 7% (10: 1 methanol / NH3 (aC) conc.) In DCM. Evaporation of the appropriate fractions da? / - methyl -? / -. { 2 - [(4-Oxo-3,4-dihydroquinazolin-5-yl) oxy] ethyl} Acetamide as a white foam (970 mg, 99%); NMR spectrum (DMSO-d6,400 MHz, 373K) 2.05 (bs, 3H), 2.92 (s, 3H), 3.71 (b, 2H), 4.20 (bi, 2H), 7.01 (d, 1 H), 7.1 9 (d, 1 H), 7.63 (dd, 1 H), 7.89 (s, 1 H); Mass Species M * NH4 * 284.0 (ES-) M-H * 260.0. ? / - Meíil -? / -. { 2 - [(4-Oxo-3,4-dihydroquinazolin-5-yl) oxy] ethyl} Acetamide (261 mg, 1.00 mmol) and diisopropylethylamine (522 μl, 3.00 mmol) are dissolved in DCM (25 ml), and the mixture is cooled to 0 ° C. Phosphorus oxychloride (930 μl, 10 mmol) is added dropwise; The solution is heated to room temperature and stirred for 2 hours. The mixture is cooled to 0 ° C and saturated sodium hydrogen carbonate solution (30 ml) is added with vigorous stirring. The stirred mixture is allowed to warm to room temperature for 20 minutes. The DCM layer is separated, rinsed with saturated sodium hydrogen carbonate solution (30 ml), water (30 ml) and brine (30 ml), filtered through silica-treated filter paper, and evaporated to give ? / -. { 2 - [(4-chloroquinazolin-5-yl) oxy] ethyl} -? / - methylacetamide as a yellow solid (90 mg, 32%); NMR spectrum (DMSO-d6,400 MHz, CDCI3) 2.05 (s, 3H), 3.17 (s, 3H), 3.85 (í, 2H), 4.28 (í, 2H), 6.99 (d, 1 H), 7.58 ( d, 1 H), 7.76 (dd, 1 H), 8.87 (s, 1 H); Mass Spectrum 276.4MH4 (product derived from 4-OMe tempered with MeOH in instrument). Example 127 N-. { 2 - [(4- { [3-Chloro-4- (1-methyl-l-pyridin-2-ylethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] ethyl} -N-methylacetarnide The procedure described in Example 126 is repeated using? / -. { 2 - [(4-chloroquinazolin-5-yl) oxy] eyl} -? / - meitylacetamide (obtained as described in Example 126, preparation of starting materials, 47 mg, 0.170 mmol) and 3-chloro-4- (1-methyl-1-pyridin-2-ylethoxy) aniline (49 mg , 0.187 mmol) to give the title compound in 31% yield; NMR spectrum (DMSO-d6,400 MHz, 373k) 1.75 (s, 6H), 1.92 (s, 3H), 2.94 (s, 3H), 3.88 (t, 2H), 4.47 (t, 2H), 6.62 (d , 1H), 7.16 (d, 1H), 7.31 (ddd, 1H), 7.35 (d, 1H), 7.39 (dd, 1H), 7.70 (dd, 1H), 7.75 (dd, 1H), 7.83 (ddd, 1H), 7.99 (d, 1H), 8.46 (s, 1H), 8.58 (dd, 1H), 9.70 (s, 1H); Mass Spectrum MH * 506.0. 3-Chloro-4- (1-methyl-1-pyridin-2-ylefoxy) aniline used as starting material is prepared as follows: Sodium hydride (60% dispersion in mineral oil, 220 mg, 5.50 mmol) is suspended in DMA (30 ml) and 2-pyridin-2-ylpropan-2-ol (obtained as described in Organomeallics, 1997, 16, 3303, 754 mg, 5.50 mmol) is added under a nitrogen aosphere. The mixture is stirred for 30 minutes at ambient temperature, then cooled to 0 ° C. 3-chloro-4-fluoronitrobenzene (878 mg, 5.00 mmol) is added as a solution in DMA (15 ml); The mixture is heated to room temperature, and stirred for 2 hours. The mixture is concentrated in vacuo, and the residue is partitioned between acetyl ether (75 ml) and water (75 ml). The aqueous layer is extracted with ethyl acetate (75 ml), and the exoractions are combined with the organic layer. The combined organics are dried over MgSO and concentrated in vacuo. The residue is purified by chromatography, eluting with 0 to 20% ethyl acetate in hexane, giving 2- [1- (2-chloro-4-nitrophenoxy) -1-methylethylpyridine as a pale yellow solid (810 mg , 55%) NMR spectrum (DMSO-d6.400 MHz, CDCI3) 1.91 (s, 6H), 6.40 (d, 1H), 7.25 (ddd, 1 H), 7.50 (d, 1 H), 7.70 (ddd, 1 H), 7.82 (dd, 1 H), 8.30 (d, 1 H), 8.65 (d, 1 H); Mass Spectrum MH * 293.0, 295.0. 2- [1- (2-Chloro-4-nitrophenoxy) -1-methylethyl] pyridine (800 mg, 2.74 mmol) is dissolved in ethyl acetate (50 ml). The mixture is purged with nifrogen, and platinum on activated carbon (10%, 100 mg) is added. The mixture is hydrogenated for 6 hours using a pipette filled with hydrogen. The system is degassed and purged with nitrogen, and the catalyst is removed by filtration. The filtrate is concentrated in vacuo, and the residue is purified by chromatography, eluting with 20% to 30% ethyl acetate in / so-hexane. The appropriate fractions are evaporated to give 3-chloro-4- (1-methyl-1-pyridin-2-yl] ethoxy) aniline as a straw colored oil (452 mg, 63%); NMR spectrum (DMSO-d6,400 MHz, CDCI3) 1.63 (s, 6H), 3.41 (bs, 2H), 6.25 (dd, 1 H), 6.35 (d, 1 H), 6.65 (d, 1 H) ), 7.1 1 (ddd, 1 H), 7.63 (ddd, 1 H), 7.77 (d, 1 H), 8.50 (d, 1 H). Example 128 Pharmaceutical Compositions The following illustrates representative pharmaceutical dosage forms of the invention as defined herein (the active ingredient termed "Compound X") that can be prepared, for therapeutic or prophylactic use in humans: (a) Tablet I mg / tablet Compound X 100 Lactose, Ph. Eur 1 82.75 Croscarmellose sodium 12.0 Passage of corn starch (5% w / v pass) 2.25 Magnesium stearate 3.0 (b) Injection I (50 mg / ml) Compound X 50% w / v 1 M Solution of sodium hydroxide 15.0% v / v 0.1 M hydrochloric acid (to adjust ph to 7.6) Polyethylene glycol 400 4.5% w / v Water for injection at 1 00%. The above compositions can be prepared by conventional procedures well known in the pharmaceutical art. For example, Tablet I can be prepared by mixing the components together and compressing the mixture into a tablet.

Claims

1. A quinazoline derivative of the formula wherein: m is 0, 1 or 2; each R1, which may be the same or different, is selected from hydroxy, alkoxy (1-6C), cycloalkyl (3-7C) -oxi and cycloalkyl (3-7C) -alcoxy. (1 -6C), and wherein any CH2 or CH3 group in a substituent R1 optionally carries in each of said group CH2 or CH3 one or more substituents of alkyl (1-6C) or halogen, or a substituent selected from hydroxy and alkoxy (1-6C), R2 is hydrogen or alkyl (1-4C); n is 0, 1, 2, 3 or 4; each R3, which may be the same or differentiate, is selected from cyano, halogen, alkyl (1-4C), trifluoromethyl, alkoxy (1-4C), alkenyl (2-4C) and alkynyl (2-4C); X1 is selected from O, S, SO, SO2, N (R7), CH (OR7), CON (R7), N (R7) CO, SO2N (R7), N (R7) SO2, OC (R7) 2, C (R7) 2O, SC (R7) 2, C (R7) 2S, CO, C (R7) 2N (R7) ) and N (R7) C (R7) 2, wherein each R7, which may be the same or different, is hydrogen or (1-6C) alkyl; Q1 is aryl, or heteroaryl, and wherein Q1 optionally bears one or more substituents, which may be the same or different, selected from halogen, cyano, nitro, hydroxy, amino, carboxy, carbamoyl, sulfamoyl, formyl, mercapto, alkyl ( 1-6C), alkenyl (2-8C), alkynyl (2-8C), alkoxy (1-6C), alkenyloxy (2-6C), alkynyloxy (2-6C), alkylthio (1-6C), alkylsulfinyl (1 -6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, alkoxycarbonyl (1-6C), IN-alkylcarbamoyl (1-6C), N, _N- di- [(1-6C) alkyl] carbamoyl, (2-6C) alkanoyl, (3-6C) alkenoyl, (3-6C) alkynyl, (2-6C) alkanoyloxy, (2-6C) alkanoylamino, JN-alkyl (1-6C) -alkanoylamino (2-6C), alkenoylamino (3-6C), JN-alkyl (1-6C) -alkenoylamino (3-6C), alkynylamino (3-6C), JN-alkyl (1-6C) ) -alkynylamino (3-6C), N-alkylsulfamoyl (1-6C), N, N-di- [(1-6C) alkyl] sulfamoyl, alkanesulfonylamino (1-6C), JN-alkyl (1-6C) - alkanesulfonylamino (1-6C) and a group of the formula: -X2-R8 wherein X2 is a direct bond or is selected O, CO and N (R9), wherein R9 is hydrogen or (1-6C) alkyl, and R8 is halo (1-6C) alkyl, hydroxy (1-6C) alkyl, carboxy-alkyl (1) -6C), alkoxy (1-6C) -alkyl (1-6C), cyano-alkyl (1-6C), amino-alkyl (1-6C), JN-alkylamino (1-6C) -alkyl (1-6C) ), JN, JN-di [(1-6C) alkyl] amino (1-6C) alkyl, (2-6C) alkanoylamino (1-6C) alkyl, JN-alkyl (1-6C) -alkylamino (2) -6C) -alkyl (1-6C), alkoxycarbonylamino (1-6C) -alkyl (1-6C), carbamoyl-alkyl (1-6C), N-alkylcarbamoyl (1-6C) -alkyl (1-6C), JN, J __- d¡ [alkyl (1-6C)] carbamoyI- (1-6C) alkyl, alkylthio (1-6C) -alkyl (1-6C), alkylsulfinyl (1-6C) -alkyl (1- 6C), alkylsulfonyl (1-6C) -alkylsulfamoyl (1-6C) alkyl (1-6C), JN-alkylsulfamoyl (1-6C) alkyl (1-6C), N, N-di-alkylsulfamoyl (1- 6C) alkyl (1-6C), alkanoyl (2-6C) -alkyl (1-6C), alkanoyloxy (2-6C) -alkyl (1-6C) or alkoxycarbonyl (1-6C) -alkyl (1-6C) , and wherein any CH2 or CH3 group in -X1-Q1 optionally carries in each said CH2 or CH3 group one or more halogen substituents ene or alkyl (1-6C) or a substi tuyenle selected from hydroxy, cyano, amino, alkoxy (1-4C), alkylamino (1-4C) and di- [alkylamino (1-4C)]; R4, R4a, R5 and R5a, which may be the same or different, are selected from hydrogen and alkyl (1-6C), or R4 and R4a together with the carbon atom to which they are attached form a cycloalkyl ring (3- 7C), or R5 and R5a together with the carbon atom to which they are attached form a cycloalkyl (3-7C) ring, and wherein any CH2 or CH3 group in any of R4, R4a, R5 and R5a optionally bears in each said CH2 or CH3 group one or more halogen substituents or a substituent selected from hydroxy, cyano, (1-6C) alkoxy, amino, (2-6C) alkanoyl, (1-6C) alkylamino and di- [(1-6C) alkylamino] )]; R6 is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C), cycloalkenyl ( 3-7C), cycloalkenyl (3-7C) -alkyl (1-6C), heterocyclyl, and heterocyclyl-alkyl (1-6C), and wherein any heterocyclyl group in a substituent R6 optionally carries one or more substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy ( 1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, alkanoyl (2-6C) ), alkanoyloxy (2-6C) and a group of the formula: wherein X3 is a direct bond or is selected from O, CO, SO2 and N (R11), wherein R11 is hydrogen or alkyl (1-4C) , and R10 is halo (1-4C) alkyl, hydroxy (1-4C) alkyl, (1-4C) alkoxy- (1-4C) alkyl, cyano (1-4C) alkyl, amino-alkyl (1) -4C), N-alkylamino (1-4C) -alkyl (1-4C), and JN, N-di- [(1-4C) alkyl] amino-alkyl (1-4C), and wherein any heterocyclic group in a substituent R6 optionally carries 1 or 2 oxo or thioxo substituents; and wherein any CH2 or CH3 group in a substiluyeníe R6, different from a group CH2 in a heterocyclyl group, optionally carries in each said group CH2 or CH3 one or more substituents of halogen or alkyl (1-6C) or a substituent selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1 -6C), alkylamine (1-6C), di- [(1-6C) alkyl] amino, JN-alkylcarbamoyl (1-6C), N, JN-di [(1-6C) alkyl] carbamoyl, alkanoyl (2C) -6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), JN-alkyl (1-6C) -alkylamino (2-6C), N-alkylsulfamoyl (1-6C), JN, N-di [alky] (1-6C)] sulfamoyl, alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C); A is selected from hydrogen, a group of the formula Z- (CR12R13) P- and R14, wherein p is 1, 2, 3, or 4, each R12 and R13, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl (2) -6C), or a group R12 and R13 linked to the same carbon atom form a cycloalkyl ring (3-7C) or cycloalkenyl (3-7C), and wherein any CH2 or CH3 group in any of R12 and R13 optionally bears in each said group CH2 or CH3 one or more substituents of halogen or alkyl (1-6C) or a substituent selected from hydroxy, cyano, alkyl (1-6C), alkoxy (1-6C), amino, alkanoyl (2-6C) ), alkylamino (1-6C) and di- [(1-6C) alkyl] amino, Z is selected from hydrogen, OR15, NR16R17, alkylsulfonyl (1-6C), alkanesulfonylamino (1-6C) and JN-alkyl (1 -6C) -alkanosulfonylamino (1-6C), wherein each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C) and alkoxycarbonyl (1-6C), or Z is a group of the formula: Q2-X4-wherein X4 is selected a of O, N (R18), SO2 and SO2N (R18), where R18 is hydrogen or alkyl (1-6C), and Q2 is cycloalkyl (3-7C), cycloalkenyl (3-7C) or heterocyclyl, R4 is selected from hydrogen, OR19 and NR16R17, wherein R1 9 is selected from alkyl (1 -6C), alkenyl (2-6C) and alkynyl (2-6C), and wherein R16 and R17 are as defined above, or R14 is a group of the formula: Q3-X5-wherein X5 is selected of O and N (R20), wherein R20 is hydrogen or alkyl (1-6C), and Q3 is cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C), cycloalkenyl (3-7C) ), cycloalkenyl (3-7C) -alkyl (1-6C), heterocyclyl and heterocyclyl-alkyl (1-6C), or R14 is Q4 wherein Q4 is cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1 -6C), cycloalkenyl (3-7C), cycloalkenyl (3-7C) -alkyl (1 -6C), heterocyclyl or heterocyclyl-alkyl (1-6C), and wherein adjacent carbon atoms in any alkylene chain (2-6C) in a substituent Z or R14 are optionally separated by the insertion in the chain of a selected group of O, S, SO, SO2, N (R21), CO, -C = C and -C = C- , wherein R21 is hydrogen or alkyl (1-6C), and wherein any heterocyclyl group in a substituent Z or R14 optionally bears one or more substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, (2-6C) alkanoyl, (2-6C) alkanoyloxy and a group of the formula: -X6- R22 wherein X6 is a direct bond or is selected from O, CO, SO2 and N (R23), wherein R23 is hydrogen or alkyl (1-4C), and R22 is halo-alkyl (1-4C), hydroxy- alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyanoalkyl (1-4C), amino-alkyl (1-4C), N-alkylamino (1-4C) -alkyl ( 1-4C), and N, N-di [(1-4C) alkyl] amino (1-4C) alkyl, and wherein any heterocyclyl group in a Z or R14 substituent optionally carries 1 or 2 oxo or thioxo substituents,and wherein any CH2 or CH3 group in a group Z or R14, other than a CH2 group in a heterocyclyl ring, optionally carries in each said CH2 or CH3 group one or more halogen substituents or (1-6C) alkyl or a substituent selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, JN-alkylcarbamoyl (1-6C), N, N-di [(1-6C) alkyl] carbamoyl, alkanoyl (2-6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), JN-alkyl (1-6C) -alkanoylamino (2-6C), JN-alkylsulfamoyl (1-6C), JN, JN- di [(1-6C) alkyl] sulfamoyl, (1-6C) alkanesulfonylamino, and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C); or a pharmaceutically acceptable salt thereof.

2. A quinazoline derivative according to claim 1, characterized in that: m is 0, 1 or 2; each R1, which may be the same or different, is selected from hydroxy, (1-6C) alkoxy, (3-7C) cycloalkyl- and cycloalkyl (3-7C) -alkoxy (1-6C), and wherein any group CH2 or CH3 in a substituent R1 optionally carries in each said group CH2 or CH3 one or more substituents of halogen or alkyl (1-6C), or a substituent selected from hydroxy and (1-6C) alkoxy, R2 is hydrogen or alkyl (1 -4C); n is 0, 1, 2, 3 or 4; each R3, which may be the same or different, is selected from halogen, alkyl (1-4C), trifluoromethyl, alkoxy (1-4C), alkenyl (2-4C) and alkynyl (2-4C); X1 is selected from O, S, SO, SO2, N (R7), CH (OR7), CON (R7), N (R7) CO, SO2N (R7), N (R7) SO2, OC (R7) 2, C (R7) 2O, SC (R7) 2, C (R7) 2S, CO, C (R7) 2N (R7) and N (R7) C (R7) 2, wherein each R7, which may be the same or different, it is hydrogen or alkyl (1-6C); Q1 is aryl, or heeroaryl, and wherein Q1 optionally bears one or more substituents, which may be the same or different, selected from halogen, cyano, nitro, hydroxy, amino, carboxy, carbamoyl, sulfamoyl, formyl, mercapto, alkyl ( 1 -6C), alkenyl (2-8C), alkynyl (2-8C), alkoxy (1-6C), alkenyloxy (2-6C), alkynyloxy (2-6C), alkylthio (1-6C), alkylsulfinyl (1 -6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, alkoxycarbonyl (1-6C), JN-alkylcarbamoyl (1-6C), JN, JN- di- [alkyl (1-6C)] carbamoyl, alkanoyl (2-6C), alkenoyl (3-6C), alkynylo (3-6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), JN-alkyl (1 -6C) -alkanoylamino (2-6C), alkenylamino (3-6C), JN-alkyl (1 -6C) -alkenoylamino (3-6C), alkynylamino (3-6C), N-alkyl (1-6C) ) -alkynylamino (3-6C), _J_-alkylsulfamoyl (1 -6C), JN, N-di- [alkyl (1 -6C)] sulfamoyl, alkanesulfonylamino (1 -6C), N.- alkyl (1 -6C) -alkanesulfonylamino (1-6C) and a group of the formula: -X2-R8 wherein X2 is a direct bond or is selected from O, CO and N (R9), wherein R9 is hydrogen or alkyl (1-6C), and R8 is halogen-alkyl (1-6C), hydroxy-alkyl (1-6C) , carboxy-alkyl (1-6C), alkoxy (1-6C) -alkyl (1-6C), cyano-alkyl (1-6C), amino-alkyl (1-6C), JN-alkylamino (1-6C) -alkyl (1-6C), JN, JN-di [alkyl (1-6C)] amino-alkyl (1-6C), alkanoylamino (2-6C) -alkyl (1-6C), JN-alkyl (1- 6C) -alkanoylamino (2-6C) -alkyl (1-6C), alkoxycarbonylamino (1-6C) -alkyl (1-6C), carbamoyl-alkyl (1-6C), JN-alkylcarbamoyl (1-6C) -alkyl (1-6C), N, N-di [(1-6C) alkyl] carbamoylalkyl (1-6C), alkylthio (1-6C) -alkyl (1-6C), alkylsulfinyl (1-6C) -alkyl (1-6C), alkylsulfonyl (1-6C) -alkylsulfamoyl (1-6C) alkyl (1-6C), N-alkylsulfamoyl (1-6C) alkyl (1-6C), N, JN-di-alkylsulfamoyl (1 -6C) alkyl (1-6C), alkanoyl (2-6C) -alkyl (1-6C), alkanoyloxy (2-6C) -alkyl (1-6C) or alkoxycarbonyl (1-6C) -alkyl (1-6C) ), and wherein any group CH2 or CH3 in -X1-Q1 optionally carries in each said group CH2 or CH3 one or more substituents of halogen or alkyl (1-6C) or a substituent selected from hydroxy, cyano, amino, (1-4C) alkoxy, alkylamino (1-4C) and di- [(1-4C) alkylamino]; R4, R4a, R5 and R5a, which may be the same or different, are selected from hydrogen and alkyl (1-6C), or R4 and R4a together with the carbon atom to which they are attached form a cycloalkyl ring (3- 7C), or R5 and R5a together with the carbon atom to which they are attached form a cycloalkyl (3-7C) ring, and wherein any CH2 or CH3 group in any of R4, R a, R5 and R5a optionally carries in each said CH2 or CH3 group one or more halogen substituents or a substituent selected from hydroxy, cyano, (1-6C) alkoxy, amino, (2-6C) alkanoyl, (1-6C) alkylamino and di- [alkylamino (1-) 6C)]; R6 is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C), cycloalkenyl ( 3-7C), cycloalkenyl (3-7C) -alkyl (1-6C), heterocyclyl and heterocyclyl-alkyl (1-6C), and wherein any heterocyclyl group in a substituent R6 optionally bears one or more substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C) , alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, (2-6C) alkanoyl, alkanoyloxy ( 2-6C) and a group of the formula: -X3-R10 wherein X3 is a direct bond or is selected from O, CO, SO2 and N (R1 1), wherein R1 1 is hydrogen or alkyl (1 - 4C), and R10 is halogen-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1 -4C), N-rent mino (1-4C) -alkyl (1-4C), and JN, JN-di- [alkyl (1-4C)] aminoalkyl (1-4C), and wherein any heterocyclyl group in a substituent R6 optionally carries 1 or 2 subsíiíuyenfes oxo or íioxo; and wherein any CH2 or CH3 group in a substituent R6, other than a CH2 group in a heterocyclyl group, optionally carries in each said CH2 or CH3 group one or more halogen substituents or alkyl (1-6C) or a substitute selected from hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1 -6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, JN-alkylcarbamoyl (1 -6C), JN, J __- di [(1-6C) alkyl] carbamoyl, alkanoyl (2C). -6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), JN-alkyl (1 -6C) -alkanoylamino (2-6C), JN-alkylsulfamoyl (1 -6C), JN, N.-di [ alkyl (1-6C)] sulfamoyl, alkanesulfonylamino (1-6C) and J __- alkyl (1-6C) -alkanesulfonylamino (1-6C); A is selected from hydrogen, a group of the formula Z- (CR12R13) P- and R14, wherein p is 1, 2, 3, or 4, each R12 and R13, which may be the same or different, is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl (2-6C), or a group R12 and R13 linked to the same carbon atom form a ring of cycloalkyl (3-7C) or cycloalkenyl (3-) 7C), and wherein any CH2 or CH3 group in any of R12 and R13 optionally carries in each said CH2 or CH3 group one or more (halogen or alkyl (1-6C) substituents or a selected substitution of hydroxy, cyano, alkyl (1-6C), (1-6C) alkoxy, amino, (2-6C) alkanoyl, (1-6C) alkylamino, and di- [(1-6C) alkyl] amino, Z is selected from hydrogen, OR15, NR16R17 , alkylsulfonyl (1-6C), alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C), wherein each of R15, R16 and R17, which may be the same or different, it is selected from hydrogen, alkyl (1-6C), alkenyl (2-6C) and alkynyl (2-6C), or Z is a group or of the formula: Q2-X4-wherein X4 is selected from O, N (R18), SO2 and SO2N (R18), wherein R18 is hydrogen or alkyl (1-6C), and Q2 is cycloalkyl (3-7C) ), cycloalkenyl (3-7C) or heterocyclyl, R14 is selected from hydrogen, OR19 and NR16R17, wherein R19 is selected from alkyl (1-6C), alkenyl (2-6C) and alkynyl (2-6C), and wherein R16 and R17 are as defined above, or R14 is a group of the formula: Q3-X5-wherein X5 is selected from O and N (R20), wherein R20 is hydrogen or alkyl (1-6C), and Q3 is cycloalkyl (3-7C), cycloalkyl (3-7C) -alkyl (1-6C), cycloalkenyl (3-7C), cycloalkenyl (3-7C) -alkyl (1-6C), heterocyclyl, heterocyclyl-alkyl (1 -6C), or R14 is Q4 wherein Q4 is cycloalkyl (3-7C), cycloalkenyl (3-7C) or heterocyclyl, and wherein adjacent carbon atoms in any alkylene chain (2-6C) in a substitute Z or R14 are optionally separated by the insertion in the chain of a selected group of O, S, SO, SO2, N (R21), CO, -C = C and -C = C-, where R21 and s hydrogen or alkyl (1-6C), and wherein any heterocyclyl group in a substituent Z or R14 optionally bears one or more (for example 1, 2 or 3) substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, formyl, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinil (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(C 1-6C)] amino, alkanoyl (2-6C), alkanoyloxy (2-6C) and a group of the formula: -X6-R22 wherein X6 is a direct bond or is selected from O, CO, SO2 and N (R23), wherein R23 is hydrogen or alkyl (1-4C), and R22 is halogen-alkyl (1) -4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino-alkyl (1-4C), N-alkylamino (1 -4C) -alkyl (1-4C), and N, N-di [(1-4C) alkyl] amino (1-4C) alkyl, and wherein any heterocyclyl group in a Z or R14 substituent optionally carries 1 or 2 substituyenfes oxo or thioxo, and in wherein any group CH2 or CH3 in a group Z or R14, other than a group CH2 in a heterocyclyl ring, optionally carries in each said group CH2 or CH3 one or more substituents of halogen or alkyl (1-6C) or a selected substiuent of hydroxy, cyano, amino, carboxy, carbamoyl, sulfamoyl, alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-) 6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, JN-alkylcarbamoyl (1-6C), JN, N-di [(1-6C) alkyl] carbamoyl, alkanoyl (2- 6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), JN-alkyl (1-6C) -alkylamino (2-6C), JN-alkylsulfamoyl (1-6C), JN, JN-di [alkyl ( 1-6C)] suIfamoil, alkanesulfonylamino (1-6C) and JN-alkyl (1-6C) -alkanesulfonylamino (1-6C); or a pharmaceutically acceptable salt thereof.

3. A quinazoline derivative according to claim 1 or claim 2, characterized in that R4, R4a, R5 and R5a, which may be the same or different, are selected from hydrogen and alkyl (1-6C), and wherein any CH2 or CH3 group in any of R4, R4a, R5 and R5a optionally carries in each said group CH2 or CH3 one or more halogen substituents or a substituent selected from hydroxy, cyano, (1-6C) alkoxy, amino, (2-6C) alkanoyl, alkylamino (1-6C) and di- [alkylamino (1-6C)].

4. A quinazoline derivative according to any of the preceding claims, characterized in that m is 0. 5. A quinazoline derivative according to any of the preceding claims, characterized in that R2 is hydrogen. 6. A quinazoline derivative according to any of the preceding claims, characterized in that n is 0, 1 or 2 and, when present, at least one R3 is in a meia position (position 3) relative to the nitrogen of the anilino group in the formula I. 7. A quinazoline derivative according to any of the preceding claims, characterized in that n is 1 and R3 is selected from halogen and alkyl (1-4C). 8. A quinazoline derivative according to the claim 7, characterized in that R3 is chloro. 9. A quinazoline derivative according to claim 7, characterized in that R3 is methyl. 10. A quinazoline derivative according to any of the preceding claims, characterized in that X1 is selected from O, S, OC (R7) 2, SC (R7) 2, SO, SO2, N (R7), CO and N (R7) C (R7) 2, wherein each R7, which may be the same or different, is hydrogen or alkyl (1-6C). eleven . A quinazoline derivative according to any of the preceding claims, characterized in that X1 is selected from O, S and OC (R7) 2 wherein each R7 is independently hydrogen or (1-6C) alkyl. 12. A quinazoline derivative according to any of the preceding claims, characterized in that X1 is OCH2. 13. A quinazoline derivative according to any of the preceding claims, characterized in that Q1 is selected from phenyl and a 5- or 6-membered monocyclic heteroaryl ring, such ring contains 1, 2 or 3 heteroatoms independently selected from oxygen, nitrogen and sulfur, and wherein Q1 optionally bears one or more substituents which may be the same or different, selected from halogen, cyano, nitro, hydroxy, amino, carboxy, carbamoyl, sulfamoyl, formyl, mercapto, alkyl (1-6C), alkenyl (2) -8C), alkynyl (2-8C), alkoxy (1-6C), alkenyloxy (2-6C), alkynyloxy (2-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1 - 6C), alkylamino (1-6C), di- [(1-6C) alkyl] amino, alkoxycarbonyl (1-6C), JN-alkylcarbamoyl (1-6C), JN, JN-di- [alkyl (1-6C) )] carbamoyl, alkanoyl (2-6C), alkenoyl (3-6C), alkynylo (3-6C), alkanoyloxy (2-6C), alkanoylamino (2-6C), JN-alkyl (1 -6C) -alkanoylamino ( 2-6C), alkenoylamino (3-6C), JN-alkyl (1-6C) -alkenoylamino (3-6C), alkynylamino (3-6C), N-alkyl (1-6C) -alkynylamino (3-6C), JN-alkylsulfamoyl (1-6C), N, JN-di- [alkyl (1 -6C)] sulfamoyl, alkanesulfonylamino (1-6C), JN-alkyl (1-6C) -alkanesulfonylamino (1-6C) and a group of the formula: -X2-R8 wherein X2 is a direct link or is selected from O, CO and N (R9), wherein R9 is hydrogen or alkyl (1-6C), and R8 is halogen-alkyl (1-6C), hydroxy-alkyl (1-6C), carboxy-alkyl (1-6C) ), (1-6C) alkoxy-(1-6C) alkyl, (1-6C) cyano-alkyl, (1-6C) amino, JN-alkylamino (1-6C) -alkyl (1-6C), JN, N.-di [(1-6C) alkyl] amino (1-6C) alkyl, (2-6C) alkanoylamino (1-6C) alkyl, N- (1-6C) alkyl-alkanoylamino (2- 6C) -alkyl (1-6C), alkoxycarbonylamino (1-6C) -alkyl (1-6C), carbamoyl-alkyl (1-6C), N-alkylcarbamoyl (1-6C) -alkyl (1-6C), JN , N-di [(1-6C) alkyl] carbamoylalkyl (1-6C), alkylthio (1-6C) -alkyl (1-6C), alkylsulfinyl (1-6C) -alkyl (1-6C), alkylsulfonyl (1-6C) -alkylsulfamoyl (1-6C) alkyl (1-6C), JN-alkylsulfamoyl (1-6C) al quil (1-6C), JN, JN-di-alkylsulfamoyl (1-6C) alkyl (1-6C), alkanoyl (2-6C) -alkyl (1-6C), alkanoyloxy (2-6C) -alkyl (1-6C) or alkoxycarbonyl (1-6C) -alkyl (1-6C), and wherein any group CH2 or CH3 in -X1-Q1 optionally bears in each said group CH2 or CH3 one or more halogen substituents or (1-6C) alkyl or a substituent selected from hydroxy, cyano, amino, (1-4C) alkoxy, alkylamino (1-4C) and di- [(1-4C) alkylamino]. 14. A quinazoline derivative according to any of the preceding claims, characterized in that Q1 is selected from phenyl, pyridyl, pyrazinyl, 1,3-thiazolyl, 1H-imidazolyl, 1 H-pyrazolyl, 1,3-oxazolyl and isoxazolyl.

5. A quinazoline derivative according to any of the preceding claims, characterized in that R6 is selected from hydrogen, alkyl (1 -3C), alkenyl (2-3C), alkynyl (2-3C), cycloalkyl (3-5C), cycloalkyl (3-5C) -alkyl (1 -3C), heterocyclyl and heterocyclyl-alkyl (1 -3C), wherein any heterocyclyl group in R6 is a partially saturated or monocyclic saturated heterocyclyl ring of 4 , 5, 6 or 7 members containing 1 or 2 selected oxygen, nihorogen and sulfur heterogenates, such a heterocyclyl group is linked to the group to which it is attached by an annular carbon atom, and wherein any heterocyclyl group on an R6 substituent optionally carries one or more substituents, which may be the same or different, selected from halogen, trifluoromethyl, cyano, nitro, hydroxy, amino, mercapto, alkyl (1-6C), alkenyl (2-6C), alkynyl (2-6C), alkoxy (1-6C), alkylthio (1-6C), alkylsulfinyl (1-6C), alkylsulfonyl (1-6C), alkylamino (1-6C), di- [(C 1-6C)] amino, alkanoyl (2C) -6C), alkanoyloxy (2-6C) and a group of the formula: -X3-R10 wherein X3 is a direct bond or is selected from O and N (R1 1), wherein R1 1 is hydrogen or alkyl ( 1 -4C), and R1 0 is halogen-alkyl (1-4C), hydroxy-alkyl (1-4C), alkoxy (1-4C) -alkyl (1-4C), cyano-alkyl (1-4C), amino -alkyl (1-4C), JN-alkylamino (1-4C) -alkyl (1-4C) and JN, JN-di- [alkyl (1-4C)] amino-alkyl (1-4C), and wherein any heterocyclyl group in a substituent R6 optionally bears 1 or 2 substituents oxo; and wherein any CH2 or CH3 group in a substituent R6, other than a CH2 group in a heterocyclyl group, optionally carries in each said CH2 or CH3 group one or more halogen substituents or alkyl (1-6C) or a substitute selected from hydroxy, amino, (1-6C) alkoxy, (1-6C) alkylamino and di- [(1-6C) alkyl] amino, 1

6. A quinazoline derivative according to claim 15, characterized in that R6 is alkyl (1-3C) ), and wherein any CH2 or CH3 group in a R6 substituent, other than a CH2 group in a heterocyclyl group, optionally carries in each said CH2 or CH3 group one or more halogen substituents or (1-6C) alkyl or a substituent selected from hydroxy, amino, (1-6C) alkoxy, (1-6C) alkylamino, and di- [(1-6C) alkyl] amino. 1

7. A quinazoline derivative according to any of the preceding claims, characterized in that A is selected from a group of the formula Z- (CR12R13) P- and R4, wherein p is 1, 2 or 3, each R12 and R13, which may be the same or different, is selected from hydrogen and alkyl (1-6C), and wherein any group CH2 or CH3 in any of R12 and R13 optionally bears in each said group CH2 or CH3 one or more halogen substituents or a substituent selected from hydroxy and (1-6C) alkoxy, Z is selected from hydrogen, OR15, NR16R17 and alkylsulfonyl (1-6C), wherein each of R15, R16 and R17, which may be the same or different, is selected from hydrogen, alkyl (1-6C), and alkoxycarbonyl (1-6C), R14 is selected from OR19 and NR16R17, wherein R19 is selected from alkyl (1-6C), and wherein R16 and R17 are as defined above, or R14 is Q4 wherein Q4 is cycloalkyl (3-7C), heterocyclyl or heterocyclyl-alkyl (1-6C), and wherein any heterocyclyl group in a Substituent Z or R14 optionally bears one or more subsfilogens, which may be the same or different, selected from halogen, hydroxy, (1-6C) alkyl and (1-6C) alkoxy, and wherein any CH2 or CH3 group in a substituent Z or R14, different from a group CH2 in a heterocyclyl group, optionally carries in each said group CH2 or CH3 one or more substituents of halogen or alkyl (1-6C) or a substituent selected from hydroxy and (1-6C) alkoxy. 1

8. A quinazoline derivative selected from one or more of the following:? / -. { 2 - [(4-. {3-Chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} -2-methoxy -? / - met Pot measured; N-. { 2 - [(4-. {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} -2- (dimethylamine not) -? / - m eyl acetamide; ? / -. { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} -2-methoxy -? / - methyl acetamide; 2-hydroxy -? / - meyil -? / -. { 2 - [(4- {3-meityl-4- (pyrazin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] eyl} acetamida; 2-hydroxy -? / - methyl -? / -. { 2 - [(4-. {3-methyl-4- (1, 3-thiazol-4-ylmethoxy) anilnino} quinazolin-5-yl) oxy] ethyl} acetamide; 2-hydroxy -? / - methyl -? / - (2 { [4- (3-methyl-4 - [(5-methylisoxazol-3-yl) methoxy] anilino) quinazolin-5-yl] oxy} ethyl) acetamide; N-. { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} -2-methoxyacetamide; ? - (2- { [4- (3-chloro-4 - [(6-methylpyridin-2-yl) methoxy] anilino) quinazolin-5-yl] oxy} ethyl) -2-hydroxy -? -methylaceaemide; ? / - ((2R) -2- { [4- (3-chloro-4 - [(6-meilypyridin-2-yl) mephoxy] anilino) quinazolin-5-yl] oxy} propyl ) -2-hydroxy -? / - melilacelamide; ? / - (2- { [4- (3-chloro-4 - [(6-meilypyridin-2-yl) methoxy] anilino) quinazolin-5-yl] oxy} ethyl) - / V-methylacetamide; ? / - (2- {[[4- (3-chloro-4 - [(2-fluorobenzyl) oxy] anilino) quinazoIin-5-yl] oxy} ethyl) -? / - methylacetamide; ? / - (2- {[[4- (3-chloro-4 - [(3-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy} ethyl) -? / -methylaceiamide; ? / -. { 2 - [(4- {3-chloro-4- (1, 3-yiazol-4-ylmefoxy) anilino} quinazolin-5-yl) oxy] efil} -? / - methylacetamide; ? / -. { 2 - [(4- {3-chloro-4- (pyrazin-2-ylmeyoxy) anilino} quinazolin-5-yl) oxy] ethyl} -? / - methylacetamide; ? / -. { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} -2-hydroxyacetamide; -. { 2 - [(4- {3-chloro-4- (pyridin-2-ylmeyoxy) anilino} quinazolin-5-yl) oxy] ethyl} -? / - methylacetamide; 2-hydroxy / -W-methyl -? / -. { 2 - [(4- {3-methyl-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / -. { (1 R) -2 - [(4. {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] -1-methyle} acef amide; ? / -. { (1 R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] -1-methylethyl} -2-hydroxyacetamide; ? / -. { 2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] etl} -2-hydroxy- / V-methylacetamide; ? / - (2- { (4- (3-chloro-4 - [(3-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy} ethyl) -2-hydroxy-β-methylacetamide;? / - { 2 - [(4- {3-chloro-4- (1, 3-thiazol-4-ylmethoxy) anilino} quinazolin-5-yl) oxy] ethyl}. 2-hydroxy -? / - methylacetamide;? / - { 2 - [(4- { 3-cl oro-4- (pyrazin-2-yl methoxy) ind. Ino.} Quin azo I in-5 -il) oxy] ei i I. -. - 2-hydroxy -? / - mefilacei amide;? / - { 2 - [(4. {3-chloro-4- (pyridin-2-ylmeyoxy) anilino .}. quinazolin-5-yl) oxy] eyl.} acef amide;? / - { (2R) -2 - [(4- { 3-chloro-4- (pyridin-2-ylmefoxy) anilino.}. quinazolin-5-yl) oxy] propyl.] acefamide;? / - { (2R) -2 - [(4- { 3-chloro-4- (pyridin-2-ylmethoxy) anilino.}. quinazolin-5-yl) oxy] propyl.} -2-hydroxy -? / - myalicylamino;? / - { (2R) -2 - [(4-. {3-chloro-4 - (pyrazin-2-ylmethoxy) anilino.} quinazolin-5-yl) oxy] propyl.) -2-h id roxy -? / - mefilacef amide;? / - ((2R) -2-. [4- (3-Chloro-4 - [(3-fluorobenzyl) oxy] anilino) quinazolin-5-yl] oxy} propyl) -2-hydroxy-β-methylacetylamide;? / -. (2R) -2 - [(4- {3- chloro-4- (1,3-thiazol-4-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} -2-hydroxy- / V-methylacetamide; ? / -. { (2R) -2 - [(4- {3-chloro-4- (pyridin-2-ylmethoxy) anilino} quinazolin-5-yl) oxy] propyl} - / V-methylacetamide; ? / -. { 2 - [(4- {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - ethyl acetate; ? / -. { 2 - [(4- {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - ethyl-2-hydroxyacetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - propyl acetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy -? / - propylacetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - isopropylacetamide; ? / -. { 2 - [(4- {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxy -? / - isopropylacetamide; ? / - alil -? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmefoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / - alíl -? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] eyl} -2-hydroxyaceiamide; ? / -. { 2 - [(4- {[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] eyl} -? / - cyclopropylaceamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - cyclopropyl-2-hydroxyacetamide; ? / -. { 2 - [(4- {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - (cyclopropylmethyl) acetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / - (cyclopropylmethyl) -2-hydroxyacetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5? / - cyclobutylazefamide; 3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-? / - cyclobutyl-2-hydroxyacetamide; 3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-? / - (1-methylpiperidin-4-yl) acetamide; 3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5- / V- (tetrahydro-2H-pyran-4-yl) acetamide; 3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5- 2-hydroxy -? / - (tetrahydro-2H-pyran-4-yl) acetamide; 3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-? / - (2-h idroxyethyl) acetamide; 3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5- 2-hydroxy -? / - (2-hydroxy-yl) acefamide; 3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-? / - (2-methoxyethyl) acetamide; 3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5- 2-hydroxy -? / - (2-meioxy-yl) -acetylamide; 3-chloro-4- (pyridin-2-ylmehoxy) phenyl] amino} quinazolin-5- -prop-2-in-1-ylacetamide; 3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5- 2-hydroxy -? / - prop-2-yn-1-ylacetamide; 3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5- 2-hydroxy -? / - mephylpropanamide; 3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-? / - mephyl-pheirahydrofuranyl-2-carboxamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmefoxy) phenyl] amino} - quinazolin-5-yl) oxy] efi l} -? /, 1 -diylmethyl prolinamide; ? / -. { 2 - [(4- {[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] efil} -2-h id roxi -? /, 2-d i meiil propan a mida; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] eyl} -1-hydroxy -? / - meilyylcyclopropanecarboxamide; ? / í-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} - / Ví,? / 2-dimethylglycine amide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -3-hydroxy- / V, 2,2-frimethylpropanamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -3-hydroxy -? / - methylpropanamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxyacetamide; ? / í-. { (2S) -2 - [(4- {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? /,? / -dimethylglycinamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazoln-5-yl) oxy] propyl} -2-methoxyacetamide; ? / -. { (2S) -2 - [(4. {[3-chloro-4- (pyridin-2-ylmefoxy) phenyl] amino} quinazolin-5-yl) oxy] pro pil} -2- (meilylsulfonyl I) acetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-hydroxyacetamide; ? /? -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazoIin-5-yl) oxy] ethyl} -? / 2,? / 2-dimethylglycanamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2-methoxy acetymida; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmefoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2- (methylsulfonyl) acetamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? -met I acetamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-h id roxi -? / - mef¡lacef amide; ? / í-. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -? / 1,? / 2,? / 2-trimethylglycinamide; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmefoxy) phenyl] amino} - chenazolin-5-yl) oxy] propyl} -2-mefoxy -? / - methylacetamida; ? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmehoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / - methyl-2- (methylsulfonyl) acetamide; -. { (2R) -2 - [(4- {[3-Cyoro-4- (pyrazin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / - mephilacelamide; ? / -. { (2R) -2 - [(4- {[3-chloro-4- (1, 3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? / - methylacetamide; ? / - ((2R) -2-. {(4- ( { 3-chloro-4 - [(3-fluorobenzyl) oxy] phenyl} amino) chenazolin-5-yl] oxy}. propyl) -? / - methylacetamide;? / - ((2R) -2-. {((4- ( { 3-chloro-4 - [(2-fluorobenzyl) oxy] phenyl}. amino) quinazolin- 5-yl] oxy}. Propyl) -? / - methyl acetamide;? / -. {(1 R) -2 - [(4- {[3-chloro-4- (pyridin- 2-ylmethoxy) phenyl] amino.}. Quinazolin-5-yl) oxy] -1-methyl-ethyl} -2-hydroxy-V-methylacetamide; ? / -. { (1 R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazoIin-5-yl) oxy] -1-methyl-ethyl} -? / - m ethyl acetamide; ? / -. { (1S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} -2-hydroxy -? / - methylacetamide; ? / -. { (1 S) -2 - [(4- {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methylethyl} -? / - methylacetam ida; ? / -. { (1 S) -2 - [(4- {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} -2-methoxy -? / - m eti I aceta mide; ? / -. { (1S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} -2-hydroxyacetamida; ? / -. { (1 S) -2 - [(4- {[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methylethyl} acetam gone; ? / í-. { (1S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} -? / 2,? / 2-dimethylglycinamide; ? / í-. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -? /,? 2-dimethyglycinamide; (2S) -? / -. { 2 - [(4. {[3-chloro-4- (pyridin-2-ylmefoxyl) phenyl] amino} quinozolin-5-yl) oxy] ethyl} -2,4-dihydroxybufanamide; (2R) -? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2,4-dihydroxybutanamide; (2R) -? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4-dihydroxybutan amide; (2S) -? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4- dihydroxybutanamide; (2R) - / V-. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4-dih id roxi bufan amida; (2S) -? / -. { (2S) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2,4-d hydroxy bufan amide; (2S) -? / -. { (1 R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} -2,4-dihydroxybutanamide; (2R) -? / -. { (1 R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1-methyl-ethyl} -2,4-dih id roxi bufan amida; (2R) - / V-. { 2 - [(4- {[3-chloro-4- (1, 3-yiazol-4-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -2, 4-d i hydroxy bufan a mida; (2S) -? / -. { 2 - [(4- {[3-chloro-4- (1, 3-thiazol-4-ylmethoxy) phenyl] amino} quinozolin-5-yl) oxy] ethyl} -2,4-dihydroxy butan amide; (2R) -A / -. { (1 R) -2 - [(4- { [3-chloro-4- (1,3-thiazol-4-lmetoxy) phenyl] amino}. Quinazolin-5-yl) oxy] -1 - meilethyl} -2,4-dihydroxybutanamide; (2S) -? / -. { (1 R) -2 - [(4- { [3-Chloro-4- (1,3-fiazol-4-ylmethoxy) phenyl] amino}. Quinazolin-5-yl) oxy] -1-methylethyl } -2,4-dihydroxybufanamide; ? / - mefil -? / -. { 2 - [(4. {[3-meityyl-4- (pyridin-2-ylmeoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / - methyl -? / -. { 2 - [(4- {[3-methyl-4- (1, 3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / - methyl -? / - (2- {[[4- ( { 3-methyl-4 - [(5-methylisoxazol-3-yl) methoxy] phenyl} amino) quinazolin-5-yl. ] oxy) acetylamide; 2-hydroxy -? / - methyl -? / -. { 2 - [(4- {[3-methyl-4- (1, 3-thiazol-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acefamide; 2-hydroxy -? / -. { 2 - [(4- {[[3-meityl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; 2-hydroxy -? / -. { 2 - [(4- {[3-methyl-4- (1, 3-yiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] -1,1-dimethylethyl} -2-hydroxyacetamide; 2-hydroxy -? / -. { (2R) -2 - [(4- {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; 2-hydroxy -? / -. { (2R) -2 - [(4- {[3-methyl-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; ? / - ((2R) -2- { [4- ( { 4 - [(3-fluorobenzyl) oxy] -3-methylphenyl}. Amino) quinazolin-5-yl] oxy} propyl ) -2-hydroxyacetamide; 2-hydroxy -? / -. { (2R) -2 - [(4- {[3-methyl-4- (1, 3-yiazol-2-ylmeyoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; ? / -. { (2R) -2 - [(4- {[[3-methyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; ? / -. { (2R) -2 - [(4- {[3-methyl-4- (1, 3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; ? / - ((2R) -2- { [4- ( { 4 - [(3-fluorobenzyl) oxy] -3-methylphenyl} amino) quinazolin-5-yl] oxy} propyl acetamide; ? / -. { (2R) -2 - [(4- {[3-methyl-4- (1, 3-thiazol-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; 2-hydroxy -? / - methyl -? / -. { (2R) -2 - [(4- {[[3-meityl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamida; 2-hydroxy -? / - mephyl -? / -. { (2R) -2 - [(4- {[3-meityl-4- (1, 3-yiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} acetamide; 2-hydroxy-? -methyl- ((2R) -2- { [4- ( { 3-methyl-4 - [(5-methylisoxazol-3-yl) -methio] -phenyl} -amino) quinazolin-5-yl. ] oxypropyl) acetylamide; ? / - meil -? / -. { (1 R) -1-methyl-2 - [(4- {[3-mephyl-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / - methyl -? / -. { (1 R) -1-methyl-2 - [(4- {[3-methyl-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / -. { (1) -2 - [(4- { [3-chloro-4- (1,3-thiazol-4-ylmethoxy) pheny] amino]. Quinazolin-5-yl) oxy] -1 -methylethyl} -2-hydroxy -? / - meth I acetamide; 2-hydroxy -? / - methyl -? / -. { (1 R) -1-methyl-2 - [(4- {[3-mephyl-4- (pyridin-2-yl-ethoxy) phenyl] -amino}. Quinazolin-5 -yl) oxy] ethyl} acetamide; 2-hydroxy -? / - methyl -? / -. { (1 R) -1-methyl-2 - [(4- {[3-methyl-4- (1,3-thiazol-4-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} acetamide; ? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -1-hydroxy-V-meitylcyclopropanecarboxamide; (2S) -? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxy -? / - methylpropanamide; ? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxy -? /, 2-dimethylpropanamide; (2R) -? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-hydroxy -? / - methylpropanamide; (2R) -? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-lmetoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -2-methoxy -? / - methylpropanamide; 2-hydroxy-V-methyl-? / - ((2R) -2- { [4 - ([3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl}. Amino) quinazolin-5-yl] oxy}. propyl) acetamide; ? / - methyl -? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-meylylpyridin-3-yl) oxy] phenyl} amino) quinazoline -5-yl] oxy}. Propyl) acetylamide; ? /? J? / 2,? / -trimethyl-N1 - ((2R) -2- { [4- ( { 3-meityl-4 - [(6-methylpyridin-3-yl) oxy] phenyl.}. amino) quinazolin-5-yl] oxy], propyl) glycinamide; ? / - methyl -? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl.} amino) quinazoline -5-yl] oxy}. Propyl) -2-pyrrolidin-1-yl acetamide; ? / - methyl -? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-mephylpyridin-3-yl) oxy] phenyl.} amino) quinazoline -5-yl] oxy}. Propyl) -2-morpholin-4-ylacetamide; ? / - methyl -? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl.} amino) quinazoline -5-yl] oxy}. Propyl) -2- (4-methylpiperazin-1-yl) acetamide; 2-hydroxy -? / - methyl -? / - ((2S) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazolin-5-yl] oxy}. propyl) acetamide; ? / - methyl- / V - ((2SJ-2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl}. amino) quinazolin- 5-yl] oxy}. Propyl) acetamide;? / -methyl-? / - ((2S) -2- { [4- (. {3-meyyl-4 - [(6-meilypyridin-3 - il) oxy] phenyl.}. amino) quinazolin-5-yl] oxy}. propyl) -2-pyrrolidin-1-ylacetamide; (2S) -2,4-dihydroxy-? / - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-meilypyridin-3-yl) oxy] phenyl} amino) quinazolin-5-yl] oxy}. propyl) butanamide; (2S) -4-bromo-2-hydroxy-N - ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl .}. amino) quinazolin-5-yl] oxy}. propyl) butanamide; ? / - (2-chloroethyl) -? / '- ((2R) -2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazolin-5-yl] oxy}. propyl) urea; 2-Hydroxy -? / - methylene N - ((1 R) -1-methyl-2 { [4- (. {3-methyl-4 - [(6-methylpyridin-3 -yl) oxy] phenyl.}. amino) quinazolin-5-yl] oxy] ethyl) acetamide; ? / - methyl -? / - ((1 R) -1-methyl-2- { [4- ( { 3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) quinazolin-5-yl] oxy} ethyl) acetamide; 2-hydroxy -? / - methyl -? / - ((1 S) -1-methyl-2 { [4- ( { 3-methyl-4 - [(6-methylpyridin-3- il) oxy) phenyl, amino) quinazolin-5-yl] oxy} ethyl) acef amide; ? -methyl-? - ((1 S) -1-methyl-2- { [4- ( { 3-meyyl-4 - [(6-mephylpyridin-3-yl) oxy] phenyl}. Amino) quinazoline-5 -yl] oxy} ethyl) acetamide; methyl-. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} methylcarbamazole; ? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmefoxy) phenyl] amine} quinazolin-5-yl) oxy ] ethyl} - / V,? / '- dimethyl urea; ? / '- (2-chloroethyl) -? / -. { 2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] eil} -? / - methylurea; ? / -. { (2R) -2 - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} - V'-methylurea; Acid [((R) -2- { 4- [3-chloro-4- (pyridin-2-ylmethoxy) phenylamino] quinazoIin-5-yloxy}. Propylcarbamoyl) methyl) methylcarbamic tert-butyl ester; ?/1-. { (2R) -2- (4- { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} quinazolin-5-yl) oxy] propyl} -N-2-methyglycinamide; 2-hydroxy -? / - methyl -? / - (2- {[[4- ( {3-methyl-4 - [(6-methylpyridin-3-yl) oxy] phenyl} amino) qu Nazolin-5-yl] oxy] ethyl) acetamide; ? / - methyl -? / - (2- { [4- ( { 3-methyl-4 - [(6-methyl-pyridin-3-yl) oxy] phenyl}. amino) quinazole -5-yl] oxy] ethyl) acetamide; and N-. { 2 - [(4- {[3-chloro-4- (1-methyl-1-pyridin-2-ylethoxy) phenyl] amino} quinazolin-5-yl) oxy] ethyl} -N-m ethyl acetamide; or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition comprising a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, as defined in any one of claims 1 to 18 in association with a pharmaceutically acceptable carrier or diluent. 20. A quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 18 for use as a medicament. twenty-one . A quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 18 for use in the production of an antimicroproliferative effect, the effect occurs only or in part by inhibiting tyrosine kinase of the erbB2 receptor in a warm-blooded animal such as human. 22. A quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 18 for use in the production of a tyrosine kinase inhibitory effect of the erbB2 receptor in a warm blood animal. as a human 23. A quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 18 for use in the production of an erbB2 receptor tyrosine kinase inhibitory effect in a warm-blooded animal such as human. 24. A process for the preparation of a quinazoline derivative of the formula I, or a pharmaceutically acceptable salt thereof, as defined in claim 1 comprising: (a) coupling, conveniently in the presence of a suitable base , of a quinazoline of the formula II: p wherein R1, R2, R3, R4, R4a, R5, R5a, R6, X1, Q1, m, and n have any of the meanings defined in claim 1 except that any functional group is protected if necessary, with a carboxylic acid of formula III, or a reactive derivative thereof: A-COOH III wherein A has any of the meanings defined in claim 1 except that any functional group is protected if necessary: or (b) for the preparation of those compounds of the formula I wherein X1 is OC (R7) 2, SC (R7) 2 or N (R7) C (R7) 2, the reaction, conveniently in the presence of a suitable base, of a quinazoline of formula IV: IV wherein X1 a is O, S or N (R7) and R, R2, R3, R4, R4a, R5, R5a, R6, R7, A, and m have any of the meanings defined in claim 1 except that any functional group is protected if necessary, with a compound of the formula V or a salt thereof: Q1-C (R7) 2-L1 V where L1 is a suitable displaceable group and Q1 and R7 have any of the meanings defined in the claim 1 except that any functional group is protected if necessary; (c) for the preparation of those compounds of the formula I wherein A is R14 and R4 is NHR17 or Q3-X5- (wherein R17 and Q3 have any of the meanings defined in claim 1 and X5 is NH), the coupling of a quinazoline of the formula II as defined up in (a) with an isocyanate of the formula I I: A-NCO Illa wherein A is R14 as previously defined in this section except that any functional group is protected if necessary; _ _ the reaction of a quinazoline of formula H where R6 is hydrogen: p wherein R1, R2, R3, R4, R4a, R5, R5a, X1, Q1, m and n have any of the meanings defined in claim 1 except that any functional group is protected if necessary, with α-hydroxy -? - butyrolactone where any functional group is protected if necessary; or e the coupling of a quinazoline of formula VI: VI wherein R1, R4, R4a, R5, R5a, R6, A and m have any of the meanings defined in claim 1 except that any functional group is protected if necessary, with a compound of the formula lb: llb wherein R2, R3, X1, Q1 and n have any of the meanings defined in claim 1 except that any functional group is protected if necessary; (f) for the preparation of those compounds of formula I wherein X 1 is O and Q 1 is 2-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 2-pyrazinyl or 3-pyridazinyl, the reaction, conveniently in the presence of a suitable base and a suitable catalyst, of a quinazoline of the formula Vi l: vp wherein R1, R2, R3, R4, R4a, R5, R5a, R6, A, m and n have any of the meanings defined in claim 1 except that any functional group is protected if necessary, with 2-bromopyridine, 4- bromopyridine, 2-chloropyrimidine, 4-chloropyrimidine, 2-chloropyrazine or 3-chloropyridazine; or (q) for the preparation of those compounds of formula I wherein A is Z- (CR12R13) P-, wherein Z is NR16R17, the reaction, conveniently in the presence of a suitable base, of a quinazoline of the formula VI H: wherein L1 is a suitable displaceable group and R, R2, R3, R4, R4a, R5, R5a, R6, R12, R1 3, X1, Q1, m, n and p have any of the meanings defined herein above except that any functional group is protected if necessary, with a compound of the formula IXa, or a reactive derivative thereof: H-NR16R17 IXa wherein R16 and R17 have any of the meanings defined in claim 1 except that any functional group is protected if it is necessary; and then, if necessary: (i) converting a quinazoline derivative of the formula I into another quinazoline derivative of the formula I; (ii) remove any protective group that is present by conventional means; (iii) forming a pharmaceutically acceptable salt.