WO2009080200A1 - Novel sulphoximide-substituted quinoline and quinazoline derivatives as kinase inhibitors - Google Patents

Abstract

Novel sulphoximide-substituted quinoline and quinazoline derivatives as kinase inhibitors The present invention relates to quinoline and quinazoline derivatives of the general formula (I) in which W, Y, R3 and R4 are indicated in the description and the claims, the use of the compounds of the general formula (I) for the treatment of various disorders, the preparation of compounds of the general formula (I), and intermediates useful in the preparation of compounds of the general formula (I).

Description

Novel sulphoximide-substituted quinoline and quinazoline derivatives as kinase inhibitors

The Invention relates to certain quinoline and quinazoline derivatives, their preparation and use as inhibitor of protein kinases, in particular of Eph (erythropoetin-βroducing hepatoma amplified sequence) receptors for the treatment of various disorders.

Protein tyrosine kinases catalyze the phosphorylation of specific tyrosine residues in various proteins. Such phosphorylation reactions play a part in a large number of cellular processes which are involved in the regulation of growth and differentiation of cells. Protein tyrosine kinases are divided into receptor and non-receptor tyrosine kinases. The family of receptor tyrosine kinases (RTKs) consists of 58 kinases (Manning G. et al. 2002, Science 298, 1912-1934). RTKs have an extracellular ligand binding domain, a transmembrane domain and an intracellular domain which usually comprises the tyrosine kinase activity. RTKs mediate signal transduction from extracellular stimulators such as, for example, growth factors. The ligand binding leads to dimerization of the RTKs and reciprocal autophosphorylation of their intracellular domains. Depending on the cell type, specific intracellular binding proteins are recruited thereby (inter alia non-receptor tyrosine kinases), via which signal processing takes place in the cell (Schlessinger J. 2000, Cell 103, 211 -225). These include receptor families of growth factors such as EGF (epidermal growth factor), VEGF (vascular endothelial growth factor), FGF (fibroblast growth factor), PDGF (platelet derived growth factor) and NGF (nerve growth factor), and of the insulin receptors, and the large family of ephrin receptors and others.

The ephrin (Eph) receptors constitute the largest family within the RTKs. They are divided according to their sequential relationship and their ligand specificity into the group of EphA receptors (9 members) and of EphB receptors (6 members) (Kullander K. and Klein R. 2002, Nat. Rev. MoI. Cell Biol. 3, 475-486; Cheng N. et al. 2002, Cyt. and growth factor Rev. 13, 75- 85.). Eph receptors are activated by membrane-associated ligands of the EphrinA or EphrinB family. EphrinAs are anchored in the cell membrane via glycolipids (GPI), whereas EphrinBs have a transmembrane region and an intracellular domain. The interaction between Ephrins and the Eph receptors leads to a bidirectional signal transmission in the ephrin-expressing and in the Eph-receptor-carrying cells. Ephrins and Eph receptors play a part in a large number of morphogenetic processes in embryonic development and in the adult organism. They are involved in embryo patterning, in the development of the blood vessel system (Gerety S.S: et al 1999, MoI. Cell 4, 403-414) and in the establishment of neuronal interconnections (Flanagan, J. G. and Vanderhaeghen, P., 1998, Annu.Rev.Neυrosci. 21, 306-354). In the adult organism, they are involved in neovascularization processes, e.g. in tumour development and in endometriosis, and in the morphogenesis of the intestinal epithelium (Batlle E. et al. 2002, Ce// 111 :251 -63.). At the cellular level, they mediate migration, adhesion and juxtacrine cell contacts. Elevated expression of Eph receptors such as, for example, EphB2 and EphB4 has also been observed in various tumour tissues such as, for example, breast and bowel tumours (Nakamoto M. and Bergemann A.D. 2002, Mic.Res.Tech. 59, 58-67). EphB2, EphB3 and EphB4 knockout mice show defects in the formation of the blood vessel system. The embryonic lethality of EphB4 -/- mice in embryonic stage d14 shows the special role of EphB4 in this process (Gerety S.S: et al 1999, Mo/. Ce// 4, 403-414). Modulation of these receptors, e.g. by inhibiting their kinase activity, leads for example to suppression of tumour growth and/or tumour metastasis either through a direct antitumour or through an indirect antiangiogenic effect.

Non-receptor tyrosine kinases occur in soluble form inside cells and are involved in the processing of extracellular signals (e.g. from growth factors, cytokines, antibodies, adhesion molecules) inside the cell. They include inter alia the families of src(sarcoma) kinases, of Tec(tyrosine kinase expressed in hepatocellular carcinoma) kinases, of Abl(Abelson) kinases and of Brk(breast tumour kinase) kinases, and the focal adhesion kinase (FAK). An altered activity of these protein tyrosine kinases may lead to a wide variety of physiological disorders in the human body and thus cause for example inflammatory, neurological and oncological disorders.

WO 01 /19828 A discloses a wide variety of kinase inhibitors.

US 2004116388 A discloses triazine compounds which inhibit receptor tyrosine kinases.

WO 03/089434 A discloses imidazo[1,2a]pyrazin-8-ylamines, and WO 04/00820 A discloses various aromatic monocycles, which inhibit receptor tyrosine kinases.

EP 0 187 705 A2 describes imidazo[4,5f]quinolines which exhibit an immunomodulating effect in infectious diseases. Likewise, US 5,506,235 A describes imidazo[4,5fjquinolines with an immunostimulating effect.

WO 04/006846 A discloses various quinazoline derivatives which inhibit receptor tyrosine kinases.

WO 03/053960 describes substituted 3-cyanoquinoline derivatives as MEK inhibitors.

US2005 /0026933 claims quinolinecarbonitriles as ERFG inhibitors.

WO 01 /68186 describes cyanoquinolines for the treatment of intestinal polyps.

However, no Eph receptor inhibitors are described among the receptor tyrosine kinase inhibitors.

It is an object of the present invention to provide compounds which inhibit receptor tyrosine kinases, especially Eph receptors. The object is achieved by quinoline and quinazoline derivatives having the general formula (I), a process for preparing the quinoline or quinazoline derivative, the uses of the quinoline or quinazoline derivative, and a medicament comprising the quinoline or quinazoline derivative, according to the following description and the claims.

The present invention relates to quinoline and quinazoline derivatives having the general formula (I) :

(I) in which:

W is equal to CH or N;

Y is equal to NR¹R² or OR¹;

R¹ and R² are identical or different and are selected one or more times independently of one another from the group comprising hydrogen, -CrC₆-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-Ci₀- cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C6-Ci2-aryl, -C5-C₁8- heteroaryl, -Ci -C₆-alkyl-Ci -Cβ-alkoxy, -Ci -C₆-alkyl-Ci -Cβ-alkoxy- C_rC₆-alkoxy, -(CH₂)n-C₆-C₁₂-aryl, -(CH₂)_n-C5-C₁₈-heteroaryl, -(CH₂)_n-C₃-Cio-cycloalkyl, -(CH₂)_n-C₃-C₁₂-heterocycloalkyl,

-phenylene-(CH₂)_p-R⁶, -(CH₂)_PPO₃(R⁶)₂, -(CH₂)_P-NR⁴C(=S)R⁵, -(CH₂)_p-NR⁴S(=O)R⁵, -(CH₂)_p-NR⁴C(=O)NR⁵R⁶, -(CH₂)_P-NR⁴C(=O)OR⁵, -(CH₂)p-NR⁴C(=NH)NR⁵R⁶, -(CH₂)_P-NR⁴C(=S)NR⁵R⁶, -(CH₂)_P- NR⁴S(=O)NR⁵R⁶, -(CH₂)_P-NR⁴S(=O)₂NR⁵R⁶, -(CH₂)_P-C(=O)R⁵, -(CH₂)_P- C(=S)R⁵, -(CH₂)_P-S(=O)R⁵, -(CH₂)_P-S(O)(NH)R⁵, -(CH₂)_P-S(O)₂R⁵, -(CH₂)p-SO₂OR⁵, -(CH₂)P-CO₂R⁵, -(CH₂)_P-CSNR⁵R⁶, -CHR⁵R⁶ and -(CH₂)_P-SR⁵ where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃- Cio-cycloalkyl, -CrCirheterocycloalkyl, -C₆-Ci₂-aryl, -C₅-Ci₈- heteroaryl or -CrC₆-alkoxy are unsubstituted or are substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, -NR⁵R⁶, -C(O)NR⁵R⁶, -S(O)₂NR⁵R⁶,

-NR⁵S(O)₂R⁶, -NR⁵C(O)R⁶, -SR⁵ , -R⁵, or -OR⁵, where the carbon framework of the -C₃-Cio-cycloalkyl and of the -C_rCi₀-alkyl may comprise one or more times independently of one another nitrogen, oxygen, sulphur atoms, -NR⁴ or C=O groups or one or more double bonds, or R¹ and R² optionally form together a bridge of 3-10 methylene units, where up to two methylene units are optionally replaced by O, S or -NR⁴, and where the phenyl radical is optionally substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, -NR⁵R⁶, alkyl or -OR⁵; in which R¹ is not hydrogen when Y is NR¹R² and R² is hydrogen; and in which R¹ is not hydrogen when Y is OR¹;

R³ is selected from the group comprising hydrogen, -Ci-C₆-alkyl,

-C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -C₆-Ci₂-aryl, -Cs-Cis-heteroaryl, C(=O)R⁵,

Q=O)NR⁵R⁶ or C(=O)OR⁵, where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂- C₆-alkynyl, -CrCio-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C₆-Ci₂- aryl or -C₅-C₁₈-heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵, C(=O)NR⁵R⁶, C(=O)OR⁵, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵,

R⁴ is selected from the group comprising -Ci-C₆-alkyl, -C₂-C₆- alkenyl, -C₂-C₆-alkynyl, -C₃-Cio-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -C₆-Ci₂-aryl, -C₅-Ci₈-heteroaryl, C(=O)R⁵, C(=O)NR⁵R⁶ or C(O)OR⁵, where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂-

C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -C₃-Ci₂-heterocycloalkyl , -C₆-Ci₂- aryl or -C₅-C₁₈-heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵, C(=O)OR⁵, C(=O)NR⁵R⁶, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵, or

R³ and R⁴ may, via the respective nitrogen atom and the respective sulphur atom to which they are attached, form a ring having a ring size of from 5 to 10 ring atoms, optionally consisting of carbon, nitrogen, oxygen or sulphur atoms;

R⁵ and R⁶ are identical or different and selected independently of one another from the group comprising hydrogen, -Ci-Cio-alkyl, -C₂- C₁₀-alkenyl, -C₂-C₁₀-alkynyl, -CrC₆-alkoxy, -C₃-Ci₀-cycloalkyl, -C₃-

Ci₂-heterocycloalkyl, -C_δ-Ci_∑-aryl and -C₅-Ci₈-heteroaryl, where -C_rCio-alkyl, -C₂-C₁₀-alkenyl, -C₂-Ci_O-alkynyl, -CrC₆-alkoxy, -C₃- Cio-cycloalkyl, -CrCu-heterocycloalkyl, -C₆-Ci₂-aryl or -C₅-C₁₈- heteroaryl are unsubstituted or one or more times independently of one another by hydroxy, halogen, cyano, nitro, -OR⁷, -NR⁷R⁸,

-C(O)NR⁷R⁸, -C(O)OR⁷ or -C_rC₆-alkyl, where -C_rC₆-alkyl is unsubstituted or one or more times independently of one another by halogen, hydroxy, cyano, -NR⁷R⁸, -OR⁷ or phenyl; or R⁵ and R⁶ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by O, S or NR⁴;

R⁷, R⁸ are identical or different and selected independently of one another from the group comprising hydrogen, -CrC₄-alkyl, -C₅- Ciβ-aryl and -Cs-Cie-heteroaryl, where -C_rC₄-alkyl, -C_δ-Cu-aryl, -C₅-Ci₈-heteroaryl is unsubstituted or one or more times independently of one another by halogen or alkoxy, or R⁷ and R⁸ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by O, S or -NR⁴; n = 1 , 2, 3, 4, 5, or 6, p = 0, 1, 2, 3, 4, 5, or 6, and the N-oxides, solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts thereof.

The groups -CrC₆-alkyl, -CrC₁₀-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-C₁₀- cycloalkyl, -CrCu-heterocycloalkyl, -C₆-C₁₂-aryl, -C₅-C₁₈-heteroaryl or -C₁ -CO- alkoxy may be substituted one or more times, in one aspect of the invention, once, twice or three times or no more often than the number of carbon atoms they have, in particular once or twice.

A preferred subgroup are compounds in which: W is equal to CH or N;

Y is equal to NR¹R² or OR¹;

R¹ is selected one or more times independently of one another from the group comprising -d-C_ό-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -CrCu-heterocycloalkyl, -C₆-Ci₂-aryl, -C₅-C₁₈- heteroaryl, -Ci -C₆-alkyl-Ci -C₆-alkoxy, -C₁ -Co-alkyl-Q -C₆-alkoxy- C_rC₆-alkoxy, -(CH₂)n-C₆-C₁₂-aryl, -(CH₂)_n-C₅-Ci₈-heteroaryl, -(CH₂)n-C₃-C₁₀-cycloalkyl, -(CH₂)_n-C₃-C₁₂-heterocycloalkyl,

-phenylene-(CH₂)_p-R⁶, -(CH₂)_PPO₃(R⁶)₂, -(CH₂)_P-NR⁴C(=S)R⁵, -(CH₂)_P-NR⁴S(=O)R⁵, -(CH₂)_P-NR⁴C(=O)NR⁵R⁶, -(CH₂)_P-NR⁴C(=O)OR⁵,

-(CH₂)_p-NR⁴C(=NH)NR⁵R⁶, -(CH₂)_P-NR⁴C(=S)NR⁵R⁶, -(CH₂),,- NR⁴S(=O)NR⁵R⁶, -(CH₂)_P-NR⁴S(=O)₂NR⁵R⁶, -(CH₂)_P-C(=O)R⁵, -(CH₂)_P- C(=S)R⁵, -(CH₂)_P-S(=O)R⁵, -(CH₂)_P-S(O)(NH)R⁵, -(CH₂)_P-S(O)₂R⁵, -(CH₂)p-SO₂OR⁵, -(CH₂)P-CO₂R⁵, -(CH₂)_P-CSNR⁵R⁶, -CHR⁵R⁶ and -(CH₂)_P-SR⁵; where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl,

-CrQo-cycloalkyl, -C₃-C₁₂-heterocycloalkyl, -C₆-C₁₂-aryl, -C₅-C₁₈- heteroaryl or -CrC_ό-alkoxy is unsubstituted or is substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, -NR⁵R⁶, -C(O)NR⁵R⁶, -S(O)₂NR⁵R⁶, -NR⁵S(O)₂R⁶, -NR⁵C(O)R⁶, -SR⁵ , -R⁵, or -OR⁵, where the carbon framework of the -C₃-C₁₀-cycloalkyl and of the -CrC₁₀-alkyl may comprise one or more times independently of one another nitrogen, oxygen, sulphur atoms, -NR⁴ or C=O groups or one or more double bonds,

R² is selected one or more times independently of one another from the group comprising hydrogen, -CrCβ-alkyl, -C₂-C₆-alkenyl, -C₂- C₆-alkynyl, -C₃-C₁₀-cycloalkyl, -Cs-C^-heterocycloalkyl, -(CH₂)_n-

C₃-do-cycloalkyl, -(CH₂)_n-C₃-Ci₂-heterocycloalkyl, and

-phenylene-(CH₂)_p-R⁶, where -Ci-C₆-alkyl, -C2-C6-alkenyl, -C₂-C₆- alkynyl, -Cs-Cio-cycloalkyl, -Cs-C^-heterocycloalkyl, -C₆-Ci₂-aryl or -Cs-C^-heteroaryl is unsubstituted, where the carbon framework of the -C₃-Cio-cycloalkyl and of the -CrCio-alkyl may comprise one or more times independently of one another nitrogen, oxygen, sulphur atoms, -NR⁴ or C=O groups or one or more double bonds; or : R¹ and R² optionally together form a bridge of 3-10 methylene units, where up to two methylene units are optionally replaced by O, S or -NR⁴, and where the phenyl radical is optionally substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, -NR⁵R⁶, alkyl or -OR⁵; R³ is selected from the group comprising hydrogen, -CrC₆-alkyl,

-C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-Cio-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -C₆-Ci₂-aryl, -Cs-Ciβ-heteroaryl, C(=O)R⁵, C(=O)NR⁵R⁶ or C(=O)OR⁵, where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂- C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -C₃-Ci₂-heterocycloalkyl , -C₆-Ci₂- aryl or -Cs-C₁₈-heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵, Q=O)NR⁵R⁶, C(=O)OR⁵, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵,

R⁴ is selected from the group comprising -CrC₆-alkyl, -C₂-C₆- alkenyl, -C₂-C₆-alkynyl, -C₃-C₁₀-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -C₆-Ci₂-aryl, -Cs-Cis-heteroaryl, C(=O)R⁵, C(=O)NR⁵R⁶ or C(=O)OR⁵, where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂- C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -C₃-C₁₂-heterocycloalkyl , -C₆-Ci₂- aryl or -C₅-C₁₈-heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(O)R⁵, C(=O)OR⁵, Q=O)NR⁵R⁶, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵, R⁵ and R⁶ are identical or different and are selected independently of one another from the group comprising hydrogen, -C_rCio-alkyl, -C₂- Cio-alkenyl, -C₂-C₁₍)-alkynyl, -C_rC₆-alkoxy, -Cs-Cio-cycloalkyl, -C₃- Ci₂-heterocycloalkyl, -C_δ-C -aryl and -Cs-Cis-heteroaryl, where -CrCio-alkyl, -C₂-Ci₀-alkenyl, -C₂-Ci_O-alkynyl, -C_rC₆-alkoxy, -C₃- Cio-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C₆-Ci₂-aryl or -C₅-Ci₈- heteroaryl are unsubstituted or one or more times independently of one another by hydroxy, halogen, cyano, nitro, -OR⁷, -NR⁷R⁸, -C(O)NR⁷R⁸, -C(O)OR⁷ or -C_rC₆-alkyl, where -C_rC₆-alkyl is unsubstituted or one or more times independently of one another by halogen, hydroxy, cyano, -NR⁷R⁸, -OR⁷ or phenyl; or

R⁵ and R⁶ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by O, S or NR⁴;

R⁷, R⁸ are identical or different and independently of one another selected from the group comprising hydrogen, -CrC₄-alkyl, -C₅-

Cie-aryl and -Cs-C^-heteroaryl, where -CrC₄-alkyl, -C_ό-Cu-aryl, -Cs-Cis-heteroaryl is unsubstituted or one or more times independently of one another by halogen or alkoxy, or R⁷ and R⁸ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by O, S or

-NR⁴; n = 1 , 2, 3, 4, 5, or 6, p = 0, 1 , 2, 3, 4, 5, or 6, and

the N-oxides, solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts thereof.

A particularly preferred subgroup are compounds in which: W is equal to CH or N;

Y is equal to NR¹R² or OR¹;

R¹ is selected one or more times independently of one another from the group comprising -CrCβ-alkyl, -C₂-C₆-alkenyl, -C₂-Cβ-alkynyl, -C₃-C₁₀-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C₆-Ci₂-aryl, -C₅-Ci₈- heteroaryl, -Ci -C₆-alkyl-Ci -C₆-alkoxy, -Ci -Ce-alkyl-C_! -C₆-alkoxy- CrC₆-alkoxy, -(CH₂)_n-C₆-Ci₂-aryl, -(CH₂)_n-C₅-Ci₈-heteroaryl, -(CH₂)_n-C₃-Cio-cycloalkyl, -(CH₂)_n-C₃-Ci₂-heterocycloalkyl,

-phenylene-(CH₂)p-R⁶, -(CH₂)_PPO₃(R⁶)₂, -(CH₂)_P-NR⁴C(=S)R⁵, -(CH₂)_p-NR⁴S(=O)R⁵, -(CH₂)p-NR⁴C(=O)NR⁵R⁶, -(CH₂)_P-NR⁴C(=O)OR⁵,

-(CH₂)_P-NR⁴C(=NH)NR⁵R⁶, -(CH₂)_P-NR⁴C(=S)NR⁵R⁶, -(CH₂)_P- NR⁴S(=O)NR⁵R⁶, -(CH₂)_P-NR⁴S(=O)₂NR⁵R⁶, -(CH₂)_P-C(=O)R⁵, -(CH₂)_P- C(=S)R⁵, -(CH₂)_P-S(=O)R⁵, -(CH₂)_P-S(O)(NH)R⁵, -(CH₂)_P-S(O)₂R⁵, -(CH₂)_P-SO₂OR⁵, -(CH₂)_p-CO₂R⁵, -(CH₂)_P-CSNR⁵R⁶, -CHR⁵R⁶ and -(CH₂)_P-SR⁵; where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl,

-C₃-Ci₀-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C₆-C₁₂-aryl, -C₅-Ci₈- heteroaryl or -CrCβ-alkoxy is unsubstituted or is substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, -NR⁵R⁶, -C(O)NR⁵R⁶, -S(O)₂NR⁵R⁶, -NR⁵S(O)₂R⁶, -NR⁵C(O)R⁶, -SR⁵ , -R⁵, or -OR⁵, where the carbon framework of the -C₃-C₁₀-cycloalkyl and of the -Ci-Ci_O-alkyl may comprise one or more times independently of one another nitrogen, oxygen, sulphur atoms, -NR⁴ or C=O groups, or one or more double bonds, R² is selected one or more times independently of one another from the group comprising hydrogen, or -CrC₆-alkyl;

R³ is selected from the group comprising hydrogen, -Ci-C₆-alkyl, -

C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-C₁₀-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -C₆-Ci₂-aryl, -Cs-Cis-heteroaryl, C(=O)R⁵, C(O)NR⁵R⁶ or C(O)OR⁵, where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂-

C₆-alkynyl, -C₃-Cκ)-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C₆-Ci₂- aryl or -C₅-Ci₈-heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵, Q=O)NR⁵R⁶, C(=O)OR⁵, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵,

R⁴ is selected from the group comprising -d-Cβ-alkyl, -C₂-C_O- alkenyl, -C₂-C₆-alkynyl, -CrCio-cycloalkyl, -C₃-C₁₂- heterocycloalkyl, -C₆-Ci₂-aryl, -C₅-Ci₈-heteroaryl, C(=O)R⁵,

C(=O)NR⁵R⁶ or C(=O)OR⁵, where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂- C₆-alkynyl, -CrCio-cycloalkyl, -C₃-C₁₂-heterocycloalkyl, -CO-C_I2- aryl or -C₅-C₁₈-heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵, C(O)OR⁵, Q=O)NR⁵R⁶, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵,

R⁵ and R⁶ are identical or different and selected independently of one another from the group comprising hydrogen, -CrCi_O-alkyl, -C₂- Cio-alkenyl, -C₂-Cio-alkynyl, -CrC₆-alkoxy, -C₃-Ci₀-cycloalkyl, -C₃- Cu-heterocycloalkyl, -C₆-Ci₂-aryl and -Cs-C^-heteroaryl, where

-CrC₁₀-alkyl, -C₂-Ci₀-alkenyl, -C₂-Ci₀-alkynyl, -d-C_δ-alkoxy, -C₃- Cio-cycloalkyl, -C₃-C₁₂-heterocycloalkyl, -C₆-Ci₂-aryl or -C₅-C₁₈- heteroaryl are unsubstituted or one or more times independently of one another by hydroxy, halogen, cyano, nitro, -OR⁷, -NR⁷R⁸, -C(O)NR⁷R⁸, -C(O)OR⁷ or -C_rC₆-alkyl, where -C_rC₆-alkyl is unsubstituted or one or more times independently of one another by halogen, hydroxy, cyano, -NR⁷R⁸, -OR⁷ or phenyl; or R⁵ and R⁶ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by 0, S or NR⁴;

R⁷, R⁸ are identical or different and selected independently of one another from the group comprising hydrogen, -CrC₄-alkyl, -C₅- ds-aryl and -Cs-Cis-heteroaryl, where -d-C₄-alkyl, -C_δ-C₁₂-aryl, -Cs-ds-heteroaryl is unsubstituted or one or more times independently of one another by halogen or alkoxy, or R⁷ and R⁸ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by 0, S or -NR⁴; n = 1 , 2, 3, 4, 5, or 6, p = 0, 1 , 2, 3, 4, 5, or 6, and

the N-oxides, solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts thereof.

A very particularly preferred subgroup are compounds in which:

W is equal to CH or N; Y is equal to NR¹R² or OR¹;

R¹ is selected one or more times independently of one another from the group comprising -CrCβ-alkyl, -C_∑-C_δ-alkenyl, -C₂-C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C₆-Ci₂-aryl, -C₅-Ci₈- heteroaryl, -Ci -C₆-alkyl-Ci -C₆-alkoxy, -Ci -C₆-alkyl-Ci -C₆-alkoxy- CrC₆-alkoxy, -(CH₂)_n-C₆-Ci2-aryl, -(CH₂)_n-C₅-Ci₈-heteroaryl,

-(CH₂)_n-C₃-C₁₀-cycloalkyl, -(CH₂)_n-C₃-Ci₂-heterocycloalkyl,

-phenylene-(CH₂)p-R⁶, -(CH₂)_PPO₃(R⁶)₂, -(CH₂)_P-NR⁴C(=S)R⁵, -(CH₂)_P-NR⁴S(=O)R⁵, -(CH₂)p-NR⁴C(=O)NR⁵R⁶, -(CH₂)_P-NR⁴C(=O)OR⁵, -(CH₂)_p-NR⁴C(=NH)NR⁵R⁶, -(CH₂)_P-NR⁴C(=S)NR⁵R⁶, -(CH₂)_P- NR⁴S(=O)NR⁵R⁶, -(CH₂)_P-NR⁴S(=O)₂NR⁵R⁶, -(CH₂)_P-C(=O)R⁵, -(CH₂)_P-

C(=S)R⁵, -(CH₂)_P-S(=O)R⁵, -(CH₂)P-S(O)(NH)R⁵, -(CH₂)_P-S(O)₂R⁵, -(CH₂)P-SO₂OR⁵, -(CH₂)p-CO₂R⁵, -(CH₂)_P-CSNR⁵R⁶, -CHR⁵R⁶ and -(CH₂)_[J-SR⁵; where -CrC₆-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -CrCio-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C₆-Ci₂-aryl, -C₅-Ci₈- heteroaryl or -C_rC₆-alkoxy is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, -NR⁵R⁶, -C(O)NR⁵R⁶, -S(O)₂NR⁵R⁶, -NR⁵S(O)₂R⁶, -NR⁵C(O)R⁶, -SR⁵ , -R⁵, or -OR⁵, where the carbon framework of the -C₃-Cio-cycloalkyl and of the -CrCio-alkyl may comprise one or more times independently of one another nitrogen, oxygen, sulphur atoms, -NR⁴ or C=O groups or one or more double bonds, R² is selected one or more times independently of one another from the group comprising hydrogen, or -C_rC₆-alkyl; R³ is selected from the group comprising hydrogen, -d-C_δ-alkyl,

-C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -Crdo-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -C₆-d₂-aryl, -Cs-dβ-heteroaryl, C(=O)R⁵, C(=O)NR⁵R⁶ or C(=O)OR⁵, where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂- C₆-alkynyl, -CrCio-cycloalkyl, -Crdrheterocycloalkyl , -C₆-Ci₂- aryl or -C₅-C₁₈-heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵, C(=O)NR⁵R⁶, C(=O)OR⁵, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵, R⁴ is selected from the group comprising -d-C_ό-alkyl, -C₂-C₆- alkenyl, -C₂-C₆-alkynyl, -C₃-C₁₀-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -C₆-Ci₂-aryl, or -Cs-dβ-heteroaryl, where -Cr C₆-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -CrCio-cycloalkyl, -C₃- Ci₂-heterocycloalkyl, -C₆-Ci₂-aryl or -C₅-C₁₈-heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵, C(=O)OR⁵, C(=O)NR⁵R⁶, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵,

R⁵ and R⁶ are identical or different and independently of one another selected from the group comprising hydrogen, -Ci-Ci_O-alkyl, -C₂- Cio-alkenyl, -C₂-Cio-alkynyl, -C_rC₆-alkoxy, -C₃-C₁₀-cycloalkyl, -C₃-

Ci₂-heterocycloalkyl, -C₆-Ci₂-aryl and -Cs-Cis-heteroaryl, where -CrCio-alkyl, -C₂-Ci₀-alkenyl, -C₂-Ci₀-alkynyl, -C_rC₆-alkoxy, -C₃- Cio-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C6-C₁₂-aryl or -Cs-C₁S- heteroaryl are unsubstituted or one or more times independently of one another by hydroxy, halogen, cyano, nitro, -OR⁷, -NR⁷R⁸,

-C(O)NR⁷R⁸, -C(O)OR⁷ or -C_rC₆-alkyl, where -C_rC₆-alkyl is unsubstituted or one or more times independently of another by halogen, hydroxy, cyano, -NR⁷R⁸, -OR⁷ or phenyl; or R⁵ and R⁶ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by O, S or

NR⁴;

R⁷, R⁸ are identical or different and independently of one another selected from the group comprising hydrogen, -CrC₄-alkyl, -C₅- Cis-aryl and -Cs-Cis-heteroaryl, where -CrC₄-alkyl, -C₆-Ci₂-aryl, -C₅-Ci₈-heteroaryl is unsubstituted or one or more times independently of one another by halogen or alkoxy, or R⁷ and R⁸ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by O, S or

-NR⁴; n = 1 , 2, 3, 4, 5, or 6, p = 0, 1 , 2, 3, 4, 5, or 6, and

the N-oxides, solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts thereof.

Even more preference is given to the following compounds:

S-[4-(3-hydroxyphenyl-1 -yl)-aminoquinolin-6-yl]-S-methylsulphoximide;

S-[4-(3-hydroxy-6-methyl-phenyl-1-yl)-aminoquinolin-6-yl]-S- methylsulphoximide;

S-[4-(3-hydroxy-5-methoxy-phenyl-1 -yl)-aminoquinolin-6-yl]-S- methylsulphoximide;

S-[4-(6-chloro-3-hydroxyphenyl-1 -yl)-aminoquinolin-6-yl]-S- methylsulphoximide;

S-[4-(3-hydroxy-5-methoxy-phenyl-1 -yl)-hydroxyquinolin-6-yl]-S- methylsulphoximide;

N,S-dimethyl-S-[4-(3-hydroxyphenyl-1 -yl)-aminoquinolin-6-yl]-sulphoximide;

N,S-dimethyl-S-[4-(3-hydroxy-6-methyl-phenyl-1 -yl)-aminoquinolin-6-yl]- sulphoximide; N,S-dimethyl-S-[4-(3-hydroxy-5-methoxyphenyl-1 -yl)-aminoquinolin-6-yl]- sulphoximide;

N-acetyl-S-[4-(3-hydroxy-5-methoxyphenyl-1 -yl)-aminoquinolin-6-yl]-S- methylsulphoximide;

N-acetyl-S-[4-(3-hydroxy-6-methylphenyl-1 -yl)-aminoquinolin-6-yl]-S- methylsulphoximide;

S-[4-(3-hydroxy-6-methylphenyl-1 -yl)-aminoquinolin-6-yl]-N-methoxy- carbonyl-S-methylsulphoximide;

S-[4-(3-hydroxy-5-methoxyphenyl-1-yl)-aminoquinolin-6-yl]-N- methoxycarbonyl-S-methylsulphoximide;

N-(ethylamino)carbonyl-S-[4-(3-hydroxy-5-methoxyphenyl-1 -yl)aminoquinolin- 6-yl]-S-methylsulphoximide;

N-(ethylamino)carbonyl-S-[4-(3-hydroxy-6-methylphenyl-1 -yl)aminoquinolin-6- yl]-S-methylsulphoximide;

S-[4-(3-hydroxy-5-methoxyphenyl-1 -yl)aminoquinazolin-6-yl]-S- methylsulphoximide;

S-[4-(3-hydroxyphenyl-1 -yl)aminoquinazolin-6-yl]-S-methylsulphoximide;

S-[4-(3-hydroxy-6-methylphenyl-1 -yl)aminoquinazolin-6-yl]-S- methylsulphoximide;

S-[4-(3-hydroxy-6-methylphenyl-1 -yl)aminoquinazolin-6-yl]-S- methylsulphoximide; It has been found that the compounds according to the invention are able to inhibit receptor tyrosine kinases, especially Eph receptors.

Alkyl means in each case a straight-chain or branched alkyl radical such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert- butyl, pentyl, isopentyl, hexyl, heptyl, octyl, nonyl and decyl.

Alkoxy means in each case a straight-chain or branched alkoxy radical such as, for example, methyloxy, ethyloxy, propyloxy, isoproplyloxy, butyloxy, isobutyloxy, sec butyloxy, pentyloxy, isopentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy or decyloxy.

The alkenyl substituents are in each case straight-chain or branched, with the following radicals being meant for example: vinyl, propen-1 -yl, propen-2-yl, but-1 -en-1-yl, but-1-en-2-yl, but-2-en-1-yl, but-2-en-2-yl, 2-methylprop-2-en- 1 -yl, 2-methylprop-1 -en-1 -yl, but-1 -en-3-yl, but-3-en-1 -yl, allyl.

Alkynyl means in each case a straight-chain or branched alkynyl radical which comprises two to six, preferably two to four, C atoms. Examples of suitable radicals are the following: ethynyl, propyn-1 -yl, propyn-3-yl, but-1 -yn-1 -yl, but-1 -yn-4-yl, but-2-yn-1 -yl, but-1 -yn-3-yl.

Cycloalkyl means monocyclic alkyl rings such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl, but also bicyclic rings or tricyclic rings such as, for example, adamantanyl. The cycloalkyl rings may be unsubstituted or substituted one or more times. Cycloalkyls according to this invention comprise C₃-Ci₂ hydrocarbon atoms; cycloalkyls having C₃-Ci₀ hydrocarbon atoms are preferred, and cycloalkyls having C₃-C_O hydrocarbon atoms are particularly preferred.

The heteroaryl radical includes an aromatic ring system which comprises in each case 5 - 18 ring atoms, preferably 5 to 10 ring atoms and particularly preferably 5 to 7 ring atoms and, instead of the carbon, one or more identical or different heteroatoms from the group of oxygen, nitrogen or sulphur. The radical may be mono-, bi- or tricyclic and additionally in each case benzo- fused. However, only those combinations which are sensible in the view of a skilled person, especially in relation to the ring tension, are meant.

The heteroaryl rings may be unsubstituted or substituted one or more times. Examples which may be mentioned are: thienyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and benzo derivatives of these radicals such as, for example, 1,3-benzodioxolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzimidazolyl, indazolyl, indolyl, isoindolyl, oxepinyl, azocinyl, indolizinyl, indolyl, isoindolyl, indazolyl, benzimidazolyl, purinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, xanthenyl etc. In this case the heteroarylrings may be attached via each carbon atom of the ring.

Halogen means in each case fluorine, chlorine, bromine or iodine. C₃-C₁₂-Heterocycloalkyl stands for an alkyl ring including 3 - 12 carbon atoms, preferably including 3 to 10 carbon atoms and particularly preferably including 3 to 6 carbon atoms, which is interrupted by at least one of the following atoms nitrogen, oxygen and/or sulphur in the ring and which may optionally be interrupted by one or more identical or different -(CO)-, -SO- or -SO₂- groups in the ring and optionally comprises one or more double bonds in the ring. However, only those combinations which are sensible in the view of a skilled person, especially in relation to the ring tension, are meant. C₃-C12- heterocycloalkyls according to this invention are monocyclic, but also bicyclic or tricyclic. Examples of monocyclic heterocycles which may be mentioned are: oxiranyl, oxethanyl, aziridinyl, azetidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, dioxolanyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, imidazolidinyl, pyrazolidinyl, dioxanyl, piperidinyl, tetrahydropyranyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, trithianyl, quinuclidinyl, azepanyl, oxepanyl etc. Examples of bicyclic and polycyclic ring systems are 7-oxabicyclo[2.2.1]heptanyl, 7-aza- bicydo[2.2.1]heptanyl, octahydroindolyl, octahydroisoindolyl, indolizidinyl, octahydroindazolyl, 1 ,4-diazabicyclo[2.2.2]octanyl or else 3-azabicyclo[3.2.1]- octanyl etc.

An aryl radical has in each case 6-12 carbon atoms. The radical may be mono- or bicyclic, for example naphthyl, biphenyl and, in particular, phenyl.

As used in this application, "C₁-C₁₀" refers, for example in connection with the definition of "CrC^-alkyl", to an alkyl group having a finite number of 1 to 10 carbon atoms, i.e. 1 , 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. The definition of "C₁-Ci_O ¹¹ is further interpreted to mean that every possible sub-range such as, for example, C1-C10, C2-C9, C3-C8, C₄-C₇, C5-C₆, C₁-C₂, C1-C3, C₁-C₄, C₁-C₅,

CrC₆, C₁-C₇, C₁-C₈, C₁-C₉, C₁-C₁₀, preferably C₁-C₂, C₁-C₃, C₁-C₄, C₁-C₅, C₁-C₆; preferably CrC₄ is also included in the definition.

In analogy thereto ¹¹C₂-C_1O ¹¹ refers, for example in connection with the definition of "CrQo-alkenyl" and '^-C^-alkynyl", to an alkenyl group or alkynyl group having a finite number of 2 to 10 carbon atoms, i.e. 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. The definition of ¹¹C₂-C_1O ¹' is interpreted to mean that every possible sub-range such as, for example, C₂-C_1O, C₃-C9, C₄-Cs, C₅-C₇, C₂-C₃, C₂-C₄, C₂-C₅, C₂-C₆, C₂-C₇, C₂-C₈, C₂-C₉, preferably C₂-C₄, is also included in the definition.

Furthermore, "C₁-C_O" refers, for example in connection with the definition of "Ci-C₆-alkoxy" to an alkoxy group having a finite number of 1 to 6 carbon atoms, i.e. 1, 2, 3, 4, 5 or 6 carbon atoms. The definition of "C₁-C₆" is interpreted to mean that every possible sub-range such as, for example, CrC₆, C₂-C₅, C₃-C₄, C₁-C₂, C₁-C₃, C₁-C₄, C₁-C₅, C₁-C₆; preferably C₁-C₄, is also included in the definition. All statements of ranges in the application which are not explicitly mentioned here are defined analogously to the ranges "C1-C10", "C2-C10" and "CrCό" mentioned above as examples.

Isomers mean chemical compounds of the same molecular formula but different chemical structure. A distinction is made in general between constitutional isomers and stereoisomers. Constitutional isomers have the same molecular formula but differ through the mode of linkage of their atoms or atomic groups. Included herein are functional isomers, positional isomers, tautomers or valence isomers. Stereoisomers have fundamentally the same structure (constitution) and thus also the same molecular formula, but differ through the spatial arrangement of the atoms. In general, configurational isomers and conformational isomers are distinguished. Configurational isomers are stereoisomers which can be interconverted only by breaking bonds. These include enantiomers, diastereomers and E/Z (cis/trans) isomers. Enantiomers are stereoisomers which are related to one another as image and mirror image and have no plane of symmetry, for example the compounds of the invention can exist either as (R)- or (S)-sulphoximide or as a mixture of (R)- and (S)- sulphoximide. All stereoisomers which are not enantiomers are referred to as diastereomers. E/Z (cis/trans) isomers at double bonds are a special case. Conformational isomers are stereoisomers which can be interconverted by rotation of single bonds. To distinguish the types of isomerism from one another, see also the IUPAC rules section E (Pure Appl. Chem. 1976, 45, 11- 30).

The quinoline and quinazoline derivatives according to the invention having the general formula (I) also encompass the possible tautomeric forms and include the E or Z isomers or, if a chiral centre is present, also the racemates and enantiomers. By these are also meant double-bond isomers.

The quinoline and quinazoline derivatives according to the invention may also exist in the form of solvates, in particular of hydrates, in which case the compounds according to the invention accordingly comprise polar solvents, in particular of water, as structural element of the crystal lattice of the compounds according to the invention. The proportion of polar solvent, in particular water, may be in a stoichiometric or else non-stoichiometric ratio. Terms used in connection with stoichiometric solvates, hydrates are also hemi-, (semi-), mono-, sesqui-, di-, tri-, tetra-, penta-, etc. solvates or hydrates.

N-Oxides means that at least one nitrogen of the compounds according to the invention of the general formula (I) may be oxidized.

If an acidic function is present, suitable salts are the physiologically tolerated salts of organic and inorganic bases such as, for example, the readily soluble alkali metal and alkaline earth metal salts, and salts of N-methylglucamine, dimethylglucamine, ethylglucamine, lysine, 1,6-hexadiamine, ethanolamine, glucosamine, sarcosine, serinol, trishydroxymethylaminomethane, aminopropanediol, Sovak base, 1-amino-2,3,4-butanetriol.

If a basic function is present, the physiologically tolerated salts of organic and inorganic acids are suitable, such as hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, oxalic acid, malonic acid, maleic acid, citric acid, succinic acid, tartaric acid and others.

Functional groups may be protected where appropriate by protective groups during the reaction sequence. Such protective groups may be inter alia esters, amides, ketals/acetals, nitro groups, carbamates, alkyl ethers, allyl ethers, benzyl ethers or silyl ethers. Compounds which may occur as constituent of silyl ethers inter alia are such as, for example, trimethylsilyl (TMS), tert- butyldimethylsilyl (TBDMS), tert-butyldiphenylsilyl (TBDPS), triethylsilyl (TES), etc. The preparation of selected intermediates provided with protective groups is described in the experimental section.

The quinoline and quinazoline derivatives according to the invention having the general formula (I) inhibit receptor tyrosine kinases, especially Eph kinases, on which their effect is also based, for example in the treatment of disorders in which angiogenesis, lymphangiogenesis or vasculogenesis are involved, of disorders of the blood vessels, disorders caused by hyperproliferation of body cells, or chronic or acute neurodegenerative disorders. The present quinoline and quinazoline derivatives having the general formula (I) can accordingly be used as medicaments.

Treatments are preferably carried out on humans, but also on related mammalian species such as, for example, dog and cat.

Angiogenic and/or vasculogenic disorders can be treated by the growth of blood vessels being inhibited (antiangiogenic) or promoted (proangiogenic).

Antiangiogenic uses take place for example in tumour angiogenesis, endometriosis, in diabetes-related or other retinopathies or in age-related macular degeneration. Proangiogenic uses take place for example in myocardial infarction or acute neurodegenerative disorders due to ischaemias of the brain or neurotraumata.

Blood vessel disorders mean stenoses, arterioscleroses, restenoses or inflammatory diseases such as rheumatoid arthritis.

Hyperproliferative disorders mean solid tumours, non-solid tumours or non- carcinogenic hyperproliferation of cells in the skin, where solid tumours mean inter alia tumours of the breast, colon, kidney, lung and/or brain. Non-solid tumours mean inter alia leukaemias, and non-carcinogenic hyperproliferation of cells in the skin means inter alia psoriasis, eczemas, scleroderma or benign prostatic hypertrophy.

Chronic neurodegenerative disorders mean inter alia Huntington's disease, amyotrophic lateral sclerosis, Parkinson's disease, AIDS-induced dementia or Alzheimer's disease. Use of the quinoline and quinazoline derivatives having the general formula (I) can likewise be used for diagnostic purposes in vitro or in vivo for identifying receptors in tissues by means of autoradiography and/or PET.

The substances can in particular also be radiolabeled for diagnostic purposes.

For use of the quinoline and quinazoline derivatives according to the invention as medicaments, they are converted into the form of a pharmaceutical product which, besides the active ingredient, comprises pharmaceutical, organic or inorganic inert carrier materials which are suitable for enteral or parenteral administration, such as, for example, water, gelatin, gum arabic, lactose, starch, magnesium stearate, talc, vegetable oils, polyalkylene glycols etc. The pharmaceutical products may be in solid form, for example as tablets, coated tablets, suppositories, capsules or in liquid form, for example as solutions, suspensions or emulsions. They additionally comprise where appropriate excipients such as preservatives, stabilizers, wetting agents or emulsifiers; salts to modify the osmotic pressure or buffers.

The present invention likewise relates to these pharmaceutical products.

Suitable for parenteral use are in particular solutions for injection or suspensions, especially aqueous solutions of the active compounds in polyhydroxyethoxylated castor oil.

Carrier systems which can also be used are surface-active excipients such as salts of bile acids or animal or vegetable phospholipids, but also mixtures thereof, and liposomes or their constituents.

Suitable for oral use are, in particular, tablets, coated tablets or capsules with talc and/or hydrocarbon carriers or binders, such as, for example, lactose, maize starch or potato starch. Use can also take place in liquid form, for example as solution, to which a sweetener is added where appropriate. The present invention likewise relates to the enteral, parenteral and oral administrations.

The dosage of the active ingredients may vary depending on the route of administration, age and weight of the patient, nature and severity of the disorder to be treated and similar factors. The daily dose is 0.5-1000 mg, it being possible to give the dose as a single dose to be administered once or divided into two or more daily doses.

The present invention likewise relates to medicaments for the treatment of the abovementioned disorders, which comprise at least one quinoline or quinazoline derivative having the general formula (I), where the medicaments may where appropriate comprise suitable formulation substances and carriers.

Where no description is given for the preparation of the starting compounds, they are known to the skilled person or can be prepared in analogy to known compounds or to processes described herein. It is likewise possible to carry out all the reactions described herein in parallel reactors or using combinatorial operating techniques.

The mixtures of isomers can be fractionated by conventional methods such as, for example, crystallization, chromatography or salt formation into the enantiomers or E/Z isomers.

Salts are prepared in a conventional way by mixing a solution of the compound having the general formula (I) with the equivalent amount or an excess of a base or acid, which is in solution where appropriate, and removing the precipitate or working up the solution in a conventional way.

The present invention likewise relates to the process for preparing the quinoline and quinazoline derivatives according to the invention. The intermediates preferably used for preparing the quinoline and quinazoline derivatives according to the invention having the general formula (I) are the following compounds having the general formulae (I) to (V).

General description of the preparation of the compounds according to the invention:

(II) (A) (I)

Scheme 1

Quinoline and quinazoline derivatives according to the invention having the general formula (I) can be prepared for example from the intermediates (II) and (A) by the route shown in Scheme 1 , in which the radical X may be for example Hal, OS(O)₂aryl or -OS(O)₂C_nF_2n+I with n= 1 -4, Hal for a halogen atom such as fluoride, chloride, bromide or iodide and the radicals R³ and R⁴ may be as described in the claims, and the radicals W and YH have the same meaning as in the general formula (I) with H as hydrogen. The required starting materials are either commercially available or are prepared by processes disclosed in the literature or in analogy to processes disclosed in the literature, or as described hereinafter.

Compounds having the general formula (I) are formed by substitution of a suitable functional group X by a nucleophile such as primary or secondary amines or alcohols, provided where appropriate with protective groups, on a compound having the general formula (II) (e.g. J. Med. Chem., 2005, 48, 3354-3363; J. Med. Chem., 1995, 38, 3482-3287). The addition of bases may in some circumstance be necessary for this reaction {J. Med. Chem., 2001 , 44, 3031 -3038). Addition of acid is likewise possible (Bioorg. Med. Chem., 2000, 8, 1415-22). Compounds of the general formula (II) with R³ ≠ hydrogen can be prepared according to Scheme 2 below:

(III) (II) Scheme 2

Starting from compounds of the general formula (III) it is possible to introduce a suitable radical R³ by reacting an appropriately reactive precursor in the presence for example of a base and/or a catalyst in a solvent which may be necessary in a temperature range between -78°C and +200⁰C. It is possible to use as suitable reactive precursor an alkyl halide such as methyl iodide, ethyl iodide, ethyl bromide or a higher homologue from the series. A suitable base which can be used is for example an amine such as triethylamine, pyridine, di(iso)-propylethylamine or else a base such as sodium hydride, potassium hydride, lithium diisopropylamine, buthyllithium or else salts such as potassium carbonate, caesium carbonate, sodium carbonate and similar bases familiar to the skilled person. It is likewise possible to use a monoalkyl or a dialkyl sulphate or an alkyl radical which is activated in another way and is known to the skilled person. Such reations are described for example in (a) S. Gaillard, C. Papamicael, G. Dupas, F. Marsais, V. Levancher, Tetrahedron 2005, 61, 8138; (b) C. BoIm, H. Villar, Synthesis 2005, 9, 1421.

It is likewise possible to use as activated radicals for example carbonyl or heterocarbonyl analogues, such as, for example, formyl chloride, acetyl chloride, acetic anhydride, methanesulphonyl chloride, ethyl isocyanate, phenyl isocyanate, phenyl isothiocyanate, methyl chloroformate. Such reactions are described for example in (a) M. Reggelin, H. Weinberger, V. Spohr, Adv. Synth. Catal. 2004, 346, 11, 1295, (b) T. Siu, A. Yudin, Org. Lett. 2002, 4, 1839, (c) V. J. Bauer, J. Orζ. Chem. 1966, 31, 3440 (d) A.C. Barnes et al., J. Med. Chem. 1979, 22, 418. Compounds of the (III) type can also be reacted by using activated aromatic or heteroaromatic ring systems in the presence of suitable transition metal catalysts to give compounds having the general formula (II). The introduction of these aromatic and heteroaromatic radicals via the sulphoximide nitrogen can be achieved by palladium-, nickel- or copper-catalyzed cross-coupling reactions. It is possible to use as activated aryl and heteroaryl radical for example a halide such as iodobenzene, bromobenzene, iodopyridine or similar radicals defined as R3 and provided with a halogen. It is likewise possible in this way to react alkenyl halides or alkynyl halides. Such reactions are described for example in (a) C. BoIm, J. P. Hildebrandt, Tetrahedron Lett. 1998, 39, 5731 -5734; b) M. Harmata, N. Parvi, Angew. Chemie 1999, 38, 2577-2579; c) C. BoIm, J.P. Hildebrandt, J. Org. Chem. 2000, 65, 169; d) C. BoIm, J.P. Hildebrand, J. Rudolph, Synthesis 2000, 911 -913; e) C. BoIm, M. Verrucci, 0. Simic, P. G. Cozzi, G. Raabe, H. Okamura, Chem. Commun. 2003, 22, 2826-2827; f) G.Y. Cho, P. Remy, J. Jansson, C. Moessner, C. BoIm, Org. Lett. 2004, 6, 3293-3296.)

Compounds of the general formula (III) can be prepared according to Scheme 3 below:

(V) (IV) (Ml)

Scheme 3

Scheme 3 shows possible ways of preparing the sulphoximide building blocks. Thioethers of the (V) type can be converted for example by oxidation with hydrogen peroxide (Synthesis 2004, 227-232) into sulphoxides of the (IV) type. Sulphoxides of the (III) type can then be converted for example by reaction with sodium azide in oleum into the sulphoximides (IV) (M. Reggelin, C. Zur, Synthesis, 2000, 1, 1 ). The reaction can be carried out in organic solvents such as, for example, chloroform. Alternative ways of preparing sulphoximides from sulphoxides or sulphides are likewise described, e.g. using the following reagents a) TSN₃ ((a) R. Tanaka, K. Yamabe, J. Chem. Soc. Chem. Commun. 1983, 329;

(b) H. Kwart, A. A. Kahn, J. Am. Chem. Soc. 1967, 89, 1959) b) N-Tosyliminophenyliodinane and cat. amounts of copper(l) triflate (J. F. K.

Mϋller, P. Vogt, Tetrahedron Lett. 1998, 39, 4805) c) Boc azide and cat. amounts of iron(ll) chlorides (T. Bach, C. Korber, Tetrahedron Lett. 1998, 39, 5015) d) o-Mesitylenesulphonylhydroxylamine (MSH) (C. R. Johnson, R. A. Kirchhoff, H. G. Corkins, J. Org. Chem. 1974, 39, 2458). e) [N-(2-(Trimethylsilyl)ethanesulphonyl)imino]phenyliodinane (Phl=NSes) (S. Cren, T. C. Kinahan, C. L. Skinner and H. Tye, Tetrahedron Lett. 2002, 43, 2749). f) Trifluoroacetamide, iodobenzene diacetate, magnesium oxide and [Rh₂(OAc)₄] (H. Okamura and C. BoIm, Org. Lett. 2004, 6, 1305). g) N-Bromosuccinimide or iodine and cyanamine in the presence of a base such as potassium tert-butoxide, followed by oxidation with meta-chloro- perbenzoic acid (m-CPBA); O. G. Mancheno, O. Bistri, C. BoIm, Organic Letters 2007, 9, 3809-11.

The thioethers of the (V) type can be prepared in analogy to for example (a) J. Med. Chem., 1994, 37, 2106; (b) Bioorg. Med. Chem. Lett., 2005, 15, 1015.

In relation to structure and configuration, sulphoximides generally have high stability (C. BoIm, J. P. Hildebrand, J. Org. Chem. 2000, 65, 169). These properties of the functional group frequently allow drastic conditions for subsequent reactions. Enantiopure sulphoximides are also employed as auxiliaries in diastereoselective synthesis ((a) S. G. Pyne, Sulfur Reports 1992, 12, 57; (b) C. R. Johnson, Aldrichchimica Acta 1985, 18, 3). The preparation of enantiopure sulphoximides is likewise described, e.g. by racemate resolution with enantiopure camphor-10-sulphonic acid ((a) C. R. Johnson, C. W. Schroeck, J. Am. Chem. Soc. 1973, 95, 7418; (b) C. S. Shiner, A. H. Berks, J. Org. Chem. 1988, 53, 5543). A further method for preparing optically active sulphoximides is the stereoselective imination of optically active sulphoxides using MSH ((a) C. BoIm, P. Mϋller, K. Harms, Acta Chem. Scand. 1996, 50, 305; (b) Y. Tamura, J. Minamikawa, K. Sumoto, S. Fujii, M. Ikeda, J. Org. Chem. 1973, 38, 1239) or trifluoroacetamide, iodobenzene diacetate, magnesium oxide and [Rh₂(OAc)₄] (H. Okamura and C. BoIm, Org. Lett. 2004, 6, 1305).

The invention further relates to quinoline and quinazoline compounds of the general formula (II) which serve as intermediates for the synthesis:

(II),

in which:

W is equal to CH or N;

X is a halogen, an OS(=O)₂R⁹ group, an OP(=O)(OR⁹)₂ group or an

(NR⁹R¹⁰R¹¹ )\τ group, where R⁹, R¹⁰ and R¹¹ is independently of one another a CrC₆-alkyl group or C₆-Ci₂-aryl group, and T is an anion such as a halide;

R³ is selected from the group comprising hydrogen, -d-Cβ-alkyl,

-C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -aryl, -heteroaryl, C(O)R⁵, C(=O)NR⁵R⁶ or C(=O)OR⁵, where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃- Cio-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -aryl or -heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵, Q=O)NR⁵R⁶, C(=O)OR⁵, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵,

R⁴ is selected from the group comprising -CrC_δ-alkyl, -C₂-C₆- alkenyl, -C₂-C₆-alkynyl, -C₃-Cio-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -aryl, -heteroaryl, C(=O)R⁵, C(=O)NR⁵R⁶ or C(=O)OR⁵, where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃- Ci₀-cycloalkyl, -C₃-Cu- heterocycloalkyl, -aryl or -heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵,

Q=O)OR⁵, Q=O)NR⁵R⁶, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵,

R⁵, R⁶ are identical or different and selected independently of one another from the group comprising hydrogen, -C_rCi₀-alkyl, -C₂- Cio-alkenyl, -C₂-Ci₀-alkynyl, -CrC₆-alkoxy, -C₃-Ci₀-cycloalkyl, -C₃- C^-heterocycloalkyl, -aryl and -heteroaryl, where -CrCio-alkyl,

-C₂-Cio-alkenyl, -C₂-Ci₀-alkynyl, -C_rC₆-alkoxy, -CrCio-cycloalkyl, -C₃-C₁₂-heterocycloalkyl, -aryl or -heteroaryl are unsubstituted or one or more times independently of one another by hydroxy, halogen, cyano, nitro, -OR⁷, -NR⁷R⁸, -C(O)NR⁷R⁸, -C(O)OR⁷ or -C_r Cβ-alkyl, where -CrC₆-alkyl is unsubstituted or one or more times independently of one another by halogen, hydroxy, cyano, -NR⁷R⁸, -OR⁷ or phenyl; or R⁵ and R⁶ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by 0, S or NR⁴; R⁷, R⁸ are identical or different and independently of one another selected from the group comprising hydrogen, -CrC₄-alkyl, -aryl and -heteroaryl, where alkyl, aryl, heteroaryl is unsubstituted or one or more times independently of one another by halogen or alkoxy, or R⁷ and R⁸ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by O, S or -NR⁴;

R⁹, R¹⁰, R¹¹ are identical or different and independently of one another selected from the group comprising -CrC₄-alkyl, -aryl and -heteroaryl, where alkyl, aryl, heteroaryl is unsubstituted or one or more times independently of one another by halogen or alkoxy, or R⁷ and R⁸ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by O, S or -NR⁴; EXPERIMENTAL SECTION:

Abbrev.: δ = chemical shift (ppm) in relation to tetramethylsilane, s = singlet, d = doublet, t = triplet, q = quartet, sep. = septet, m multiplet, dm = doublet of multiplets, bs = broad singlet THF = tetrahydrofuran L = litre g = gram DMSO = dimethyl sulphoxide RT = room temperature min. = minutes

Intermediate a): 4-Chloro-6-methanesulphinylquinoline

A solution of 62.2 g of sodium periodate in 1.2 I of water was added dropwise to a solution of 30.5 g of 4-chloro-6-methylsulphanylquinoline (Bioorg. Med. Chem. Lett. 15, (2005), pp. 1015-8) in 1.9 I of THF at RT. After 60 h, 82.5 g of sodium sulphite were added, and the mixture was stirred for a further 2 hours. Ethyl acetate was added until there was clear separation of two phases from one another. The solution was filtered and the phases were then separated. The organic phase was dried with sodium sulphate and concentrated in vacuo. The remaining oil was purified by column chromatography (silica gel, hexane/ethyl acetate/2-propanol). 25.5 g of the title compound were obtained.

¹H-NMR (DMSO-d6): δ = 2.88 (s, 3H); 7.9 (d, 1H); 8.1 (dd, 1H); 8.27 (d, 1 H); 8.51 (d, 1 H); 8.95 (d, 1 H); Intermediate b): S-(4-Chloroquinolin-6-yl)-S-methylsulphoximide

29.9 ml of oleum (20%) were added to a solution of 4-chloro-6- methanesulphinylquinoline in 116 ml of chloroform, and the internal temperature was controlled to about 45°C. Then 8 g of sodium azide were added in portions over the course of 90 minutes. After about 3 hours, the mixture was poured into ice-water and cautiously adjused to pH = 11 with sodium hydroxide. The organic phase was separated and the aqueous phase was extracted 3 times more with dichloromethane. The combined organic phases were dried with sodium sulphate and concentrated in vacuo. The remaining oil was purified by column chromatography (silica gel, hexane/ethyl acetate/2-propanol). 8.08 g of the title compound were obtained.

1H-NMR (DMSO-d6): δ = 3.43 (s, 3H); 7.95 (d, 1 H); 8.33 (d, 2H); 8.78 (dd, 1H); 9.02 (d, 1 H);

Intermediate c): S-(4-Chloroquinolin-6-yl)-S-methyl-N-(allyloxycarbonyl)sulphoximide

A solution of 3.7 g of 4-chloro-6-(S-methylsulphonimidoyl)quinoline and 1.9 ml of allyl chloroformate in 95 ml of pyridine was stirred at RT for 15 hours. The mixture was poured into 100 ml of ice-water and stirred for 10 min., and 150 ml of toluene were added. The organic phase was separated and the aqueous phase was extracted with 150 ml of toluene. The combined organic phases were shaken 1x with 100 ml of half -saturated NaHCO₃ solution and 1x with 100 ml of saturated NaCl-solution, dried over sodium sulphate and concentrated in vacuo. The remaining oil was purified by column chromatography (silica gel, dichloromethane/ethyl acetate/methanol). 4.1 g of the title compound were obtained.

¹H-NMR (DMSO-d6): δ = 3.64 (s, 3H); 4.40 (dm, 2H); 5.11 (dm, 1H); 5.19 (dm,1H); 5.81 (ddt, 1 H); 8.00 (d, 1H); 8.32 (dd, 1 H); 8.38 (d, 1 H); 8.78 (d, 1H); 9.07 (d, 1H);

Intermediate d): S-(4-Chloroquinolin-6-yl)-S,N-dimethylsulphoximide

950 mg of S-(4-chloroquinolin-6-yl)-S-methylsulphoximide were added to a suspension of 362 mg of sodium hydride in 41 ml of dimethoxyethane at RT. 0.76 ml of methyl iodide was added thereto, and the mixture was stirred at RT for 72 hours. The mixture was completely concentrated in vacuo and suspended in dichloromethane. The suspension was filtered and the organic phase was completely concentrated in vacuo. The resulting solid was purified by chromatography (silica gel, hexane/dichloromethane/methanol). 685 mg of the title compound were obtained.

¹H-NMR (CDCl₃): δ = 2.71 (s, 3H); 3.20 (s, 3H); 7.65 (d, 1H); 8.16 (dd, 1 H); 8.32 (d, 1 H); 8.89 (d, 1 H); 8.95 (d, 1H); Intermediate e): N-[(4-Chloroquinolin-6-yl)(methyl)oxido-λ⁴-sulphanylidene]acetamide

78 mg (1 mmol) of acetyl chloride were added to a solution of 200 mg (0.83 mmol) of 4-chloro-6-(S-methylsulphonimidoyl)quinoline in 1 ml of pyridine at 0°C, and the mixture was warmed to RT while stirring overnight. Subsequently a further 78 mg (1 mmol) of acetyl chloride were added, and the mixture was stirred at RT for 2 h. The mixture was purified by prep. HPLC. 49 g (20%) of the title compound were obtained. MS (ESpos): 283.3 [M+H]⁺.

Intermediate f): Methyl [(4-chloroquinolin-6-yl)(methyl)oxido-λ⁴-sulphanylidene]carbamate

94 mg (1 mmol) of methyl chloroformate were added to a solution of 200 mg (0.83 mmol) of 4-chloro-6-(S-methylsulphonimidoyl)quinoline in 1 ml of pyridine at 0⁰C, and the mixture was warmed to RT while stirring overnight. Subsequently a further 94 mg (1 mmol) of methyl chloroformate were added, and the mixture was stirred at RT for 2 h. The mixture was purified by prep. HPLC. 49 mg (20%) of the title compound were obtained. MS (ESpos): 299.0 [M+H]\ Intermediate g): 1-[(4-Chloroquinolin-6-yl)(methyl)oxido-λ⁴-sulphanylidene]-3-ethylurea

A solution of 200 mg (0.83 mmol) of 4-chloro-6-(S-methylsulphonimidoyl)- quinoline and 213 mg (3 mmol) of ethyl isocyanate in 10 ml of THF was stirred at 60° C for 3 days. The mixture was concentrated under reduced pressure, and the residue was purified by prep. HPLC. 206 mg (80%) of the title compound were obtained. MS (ESpos): 312.3 [M+H]⁺.

Example 1 : S-[4-(3-Hydroxyphenyl-1-yl)-aminoquinolin-6-yl]-S-methylsulphoximide

A solution of 65 mg of S-(4-chloroquinolin-6-yl)-S-methyl-N-(allyloxycarbonyl)- sulphoximide and 33 mg of 3-aminophenol in 3 ml of acetonitrile were stirred at 90° C for 8 hours. The solvent was completely removed in vacuo, and the residue was suspended in 1 ml of THF. 0.044 ml of morpholine and 23 mg of tetrakistriphenylphosphine palladium were added thereto. After 22 hours, the mixture was completely concentrated in vacuo and the residue was purified by flash chromatography (silica gel, dichloromethane/methanol). 83 mg of the title compound were obtained as morpholine salt.

¹H-NMR (DMSO-d6): δ = 3.01 -3.12 (m, 4H); 3.20 (s, 3H); 3.73-3.84 (m, 4H); 6.61 (dd, 1H); 6.76-6.86 (m, 2H); 7.02 (d, 1 H); 7.20 (t, 1H); 7.99 (d, 1 H); 8.12 (dd, 1H); 8.54 (d, 1 H); 9.09 (d, 1 H); The following were prepared in an analogous manner to Ex. 1 :

Example 2:

S-[4-(3-Hydroxy-6-methylphenyl-1 -yl)-aminoquinolin-6-yl]-S- methylsulphoximide

¹H-NMR (DMSO-d6): δ = 2.07 (s, 3H); 2.95-3.05 (m, 4H); 3.21 (s, 3H); 3.70-3.79 (m, 4H); 6.05 (d, 1 H); 6.73 (dd, 1H); 6.81 (d, 1 H); 7.03 (d, 1 H); 7.94 (d, 1 H); 8.10 (dd, 1H); 8.39 (d, 1H); 9.13 (d, 1H);

Example 3:

S-[4-(3-Hydroxy-5-methoxyphenyl-1-yl)-aminoquinolin-6-yl]-S- methylsulphoximide

¹H-NMR (DMSO-d6): δ = 2.93-3.02 (m, 4H); 3.20 (s, 3H); 3.68-3.76 (m, 7H); 6.18 (t, 1H); 6.41 (t, 2H); 6.46 (t, 1 H); 7.10 (d, 1 H); 7.99 (d, 1H); 8.12 (dd, 1 H); 8.56 (d, 1H); 9.06 (d, 1 H); Example 4:

S-[4-(6-Chloro-3-hydroxyphenyl-1-yl)-aminoquinolin-6-yl]-S- methylsulphoximide

0.5 ml of 4N HCl in dioxane was added to a solution of 100 mg (0.42 mmol) of 4-chloro-6-(S-methylsulphonimidoyl)quinoline and 72 mg (0.5 mmol) of 3-amino-4-chlorophenol in 5 ml of isopropanol, and the mixture was stirred at 80⁰C overnight. After cooling to RT it was diluted with acetonitrile, and the precipitate which separated out was filtered off. The precipitate was chromatographed by prep. HPLC and on silica gel. 75 mg (52%) of the title compound were obtained.

¹H-NMR (400 MHz, D6-DMSO): δ = 3.21 (s, 3H), 6.27 (bs, 1 H), 6.72-6.88 (m, 2H), 7.40 (d, 1 H), 7.98 (bs, 1 H), 8.13 (d, 1H), 8.5 (bs, 1 H), 9.05 (s, 1 H), 9.41 (bs, 1H), 9.9 (s, 1H). MS (ESpos): 348.1 [M+H]⁺.

Example 5:

S-[4-(3-Hydroxy-5-methoxyphenyl-1-yl)-hydroxyquinolin-6-yl]-S- methylsulphoximide

A solution of 100 mg (0.42 mmol) of 4-chloro-6-(S-methylsulphonimidoyl)- quinoline and 64 mg (0.46 mmol) of 3,5-dihydroxyanisole in 2.1 ml of acetonitrile was mixed with 57 mg (0.42 mmol) of potassium carbonate and stirred under reflux overnight. Cooling to RT was followed by dilution with ethyl acetate and washing 3 times with sat. sodium bicarbonate solution and sat. sodium chloride solution. The org. phase was dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by prep. HPLC. 22 mg (15%) of the title compound were obtained. 1H-NMR (400 MHz, D6-DMSO): δ = 3.25 (s, 3H), 3.73 (s, 3H), 6.29 (t, 1H), 6.35 (t, 1 H), 6.38 (t, 1H), 6.87 (d, 1 H), 8.22 (d, 1H), 8.28 (d, 1 H), 8.85-8.88 (m, 2H), 9.95 (s, 1 H). MS (ESpos): 345.1 [M+H]\

Example 6: N,S-Dimethyl-S-[4-(3-hydroxyphenyl-1-yl)aminoquinolin-6-yl]sulphoximide

A solution of 51 mg of S-(4-chloroquinolin-6-yl)-S,N-dimethylsulphoximide and 44 mg of 3-aminophenol in 3 ml of acetonitrile was stirred at 110⁰C for 22 hours. The solvent was completely removed in vacuo. The residue was separated by preparative HPLC: column: X-Bridge RP C18 30 x 100 5μM; detection: DAD TAC 200-400 nM; flow rate: 50 ml/min; mobile phase: A = 0.1% formic acid in H₂O, B = acetonitrile; 10 min. gradient. 48 mg of the title compound were obtained.

¹H-NMR (DMSO-d6): δ = 2.51 (s, 3H); 3.23 (s, 3H); 6.58 (d, 1H); 6.76-6.84 (m, 2H); 7.03 (d, 1H); 7.22 (t, 1H); 7.96-8.06 (m, 2H); 8.56 (d, 1H); 8.59 (s, 1H); 9.37 (bs, 1 H); 9.57 (bs, 1 H);

Example 7:

N,S-Dimethyl-S-[4-(3-hydroxy-6-methylphenyI-1-yl)aminoquinolin-6-yl]- sulphoximide

140.5 mg (0.552 mmol) of S-(4-chloroquinolin-6-yl)-S,N-dimethylsulphoximide were introduced into 3 ml of acetonitril at RT under an argon atmosphere. 81.5 mg (0.662 mmol) of 3-amino-4-methylphenol and 138 μl of a 4 molar solution of hydrogen chloride in 1 ,4-dioxane were added thereto, and the mixture was stirred at 80⁰C for 2 h. It was cooled to RT and, after adjustment to a basic pH with 1 -normal sodium hydroxide solution, extracted with ethyl acetate. The organic phase was washed once with saturated sodium chloride solution. It was dried over magnesium sulphate and concentrated. The crude product was purified by column chromatography on silica gel (mobile phase: dichloromethane/methanol = 10 : 1 ). The product-containing fractions were combined and concentrated. The resulting product was dried under high vacuum. 106 mg (56%) of the title compound were obtained.

¹H-NMR (400 MHz, DMSO-d6): δ = 9.40 (br. s, 1 H), 9.30 (s, 1 H), 8.99 (s, 1H), 8.47 (d, 1 H), 8.00 (q, 2H), 7.17 (d, 1 H), 6.72-6.65 (m, 2H), 6.19 (d, 1 H), 3.24 (s, 3H), 2.53 (s, 3H), 2.03 (s, 3H).

LC-MS: Rt= 0.60 min; MS (ESIpos): m/z = 342 [M+H]\

LC-MS method:

Instrument: Micromass QuattroPremier with Waters UPLC Acquity; column: Thermo Hypersil GOLD 1.9μ 50x 1 mm; eluent A: 1 I of water + 0.5 ml of 50% formic acid, eluent B: 1 I of acetonitrile + 0.5 ml of 50% formic acid; gradient: O.Omin 90%A 0.1 min 90%A 1.5min 10%A 2.2min 10%A oven:50°C; flow rate: 0.33ml/min; UV detection: 210 nm. The following were prepared in an analogous manner to Ex. 6:

Example 8:

N,S-Dimethyl-S-[4-(3-hydroxy-5-methoxyphenyl-1-yl)-aminoquinolin-6-yl]- sulphoximide

LC-MS: column: Acquity BEH C18 2.1X50 1 ,7 °M; detection: DAD TAC 200- 400 nM; flow rate: 0.8 ml/min; mobile phase: A = 0.05% formic acid in H₂O; B = acetonitrile; 2 min. gradient (A=99 / B=1 -> A=1 / B=99) 1.6 min., (A = 1 / B = 99) 0.4 min; T = 60°C MS (esi): M⁺+1 = 358 (M⁺+1 calc. = 358) RT = 0.60 min.

Example 9:

N-Acetyl-S-[4-(3-hydroxy-5-methoxyphenyl-1 -yl)-aminoquinolin-6-yl]-S- methylsulphoximide

A solution of 37 mg (0.13 mmol) of N-[(4-chloroquinolin-6-yl)(methyl)oxido-λ⁴- sulphanylidene]acetamide and 24 mg (0.16 mmol) of 3-amino-5-methoxy- phenol in 3 ml of isopropanol was mixed with 30 μl of 4 N HCl in dioxane and stirred at 80° C overnight. The solution was concentrated and dissolved in 1 ml of pyridine and, at 0⁰C, 5 μl (0.07 mmol) of acetyl chloride were added. The mixture was stirred at RT overnight and concentrated, and the residue was chromatographed on silica gel. 19 mg (35%) of the title compound were obtained. 1H-NMR (400 MHz, D6-DMSO): δ = 2.0 (s, 3H); 3.52 (s, 3H); 3.72 (s, 3H); 6.20 (t, 1 H); 6.4-6.43 (m, 2H); 7.10 (d, 1 H); 8.06 (d, 1H); 8.11 (d, 1 H); 8.6 (d, 1H); 9.07 (s, 1H);9.51 (bs, 1 H); 9.65 (s, 1 H). MS (ESpos): 386.1 [M+H]⁺.

Example 10: N-Acetyl-S-[4-(3-hydroxy-6-methylphenyl-1-yl)-aminoquinolin-6-yl]-S- methylsulphoximide

A solution of 43 mg (0.15 mmol) of N-[(4-chloroquinolin-6-yl)(methyl)oxido-λ⁴- sulphanylidene]acetamide and 22 mg (0.16 mmol) of 3-amino-4-methylphenol in 4 ml of acetonitrile and 1 ml of methanol was stirred at 150⁰C in a microwave for 135 min. The solution was concentrated and chromatographed on silica gel. 5 mg (9%) of the title compound were obtained. 1H-NMR (400 MHz, D6-DMSO): δ = 2.0 (s, 3H); 2.04 (s, 3H); 3.54 (s, 3H); 6.20 (d, 1H); 6.66-6.73 (m, 2H); 7.18 (d, 1 H); 8.03 (d, 1H); 8.09 (d, 1H); 8.5 (d, 1 H); 9.1 (s, 1 H); 9.3 (bs, 1H); 9.45 (s, 1 H). MS (ESpos): 370.0 [M+H]\

Example 11 :

S-[4-(3-Hydroxy-6-methylphenyl-1-yl)-aminoquinolin-6-yl]-N-methoxy- carbonyl-S-methylsulphoximide

A solution of 34 mg (0.11 mmol) of methyl [(4-chloroquinolin-6- yl)(methyl)oxido-λ⁴-sulphanylidene]carbamate and 17 mg (0.14 mmol) of 3-amino-4-methylphenol in 3 ml of isopropanol was mixed with 30 μl of 4 N HCl in dioxane and stirred at 80⁰C for 6 h. The solution was concentrated and chromatographed by prep. HPLC and on silica gel. 21 mg (48%) of the title compound were obtained.

¹H-NMR (400 MHz, D6-DMSO): δ = 2.08 (s, 3H); 3.51 (s, 3H); 3.67 (s, 3H); 6.38 (d, 1 H); 6.78 (d, 1 H); 6.86 (dd, 1H); 7.28 (d, 1 H); 8.25 (d, 1H); 8.45 (d, 1H); 8.56 (d, 1H); 9.5 (s, 1 H); 9.8 (bs, 1H). MS (ESpos): 386.1 [M+H]\

Example 12:

S-[4-(3-Hydroxy-5-methoxyphenyl-1-yl)-aminoquinolin-6-yl]-N-methoxy- carbonyl-S-methylsulphoximide

A solution of 34 mg (0.11 mmol) of methyl [(4-chloroquinolin-6- yl)(methyl)oxido-λ⁴-sulphanylidene]carbamate and 19 mg (0.14 mmol) of

3-amino-5-methoxyphenol in 3 ml of isopropanol was mixed with 30 μl of 4 N

HCl in dioxane and stirred at 80° C for 6 h. The solution was concentrated and chromatographed by prep. HPLC. 47 mg (95%) of the title compound were obtained. 1H-NMR (400 MHz, D6-DMSO): δ = 3.48 (s, 3H); 3.66 (s, 3H); 3.73 (s, 3H); 6.38

(d, 1H); 6.5 (d, 2H); 7.02 (d, 1 H); 8.24 (d, 1 H); 8.36 (d, 1 H); 8.60 (d, 1H);

9.41 (s, 1H); 9.98 (bs, 1H). MS (ESpos): 402.1 [M+H]\ Example 13: N-(Ethylamino)carbonyl-S-[4-(3-hydroxy-5-methoxyphenyl-1-yl)- aminoquinolin-6-yl]-S-methylsulphoximide

A solution of 100 mg (0.32 mmol) of 1 -[(4-chloroquinolin-6-yl)(methyl)oxido- λ⁴-sulphanylidene]-3-ethylurea and 60 mg (0.39 mmol) of 3-amino-5- methoxyphenol in 3 ml of isopropanol was mixed with 30 μl of 4 N HCl in dioxan and stirred at 80⁰C overnight. The solution was concentrated and chromatographed by prep. HPLC and on silica gel. 88 mg (65%) of the title compound were obtained.

¹H-NMR (400 MHz, D6-DMSO): δ = 0.96 (t, 3H); 2.93 (m, 2H); 3.50 (s, 3H); 3.75 (s, 3H); 6.43 (t, 1H); 6.5 (d, 2H); 6.98 (d, 1 H); 8.22 (d, 1 H); 8.39 (d, 1 H); 8.59 (d, 1H); 9.41 (s, 1 H); 10.03 (bs, 1 H), 11.4 (s, 1 H). MS (ESpos): 415.2 [M+H]\

Example 14:

N-(Ethylamino)carbonyl-S-[4-(3-hydroxy-6-methylphenyl-1-yl)- aminoquinolin-6-yl]-S-methylsulphoximide

A solution of 100 mg (0.32 mmol) of 1 -[(4-chloroquinolin-6-yl)(methyl)oxido- λ⁴-sulphanylidene]-3-ethylurea and 47 mg (0.39 mmol) of 3-amino-4- methylphenol in 5 ml of isopropanol was mixed with 50 μl of 4 N HCl in dioxane and stirred at 80⁰C for 6 h. The resulting precipitate was filtered off with suction and dried under high vacuum. 87 mg (62%) of the title compound were obtained as hydrochloride salt.

¹H-NMR (400 MHz, D6-DMSO): δ = 0.96 (t, 3H); 2.09 (s, 3H); 2.93 (m, 2H); 3.50 (s, 3H); 3.58 (s, 3H); 6.37 (t, 1H); 6.77 (d, 1H); 6.85 (dd, 1H); 7.08 (t, 1H); 7.28 (d, 1H); 8.20 (d, 1 H); 8.39 (d, 1 H); 8.55 (d, 1H); 9.42 (s, 1 H); 9.75 (bs, 1 H); 11.35 (bs, 1 H), 14.6 (s, 1 H). MS (ESpos): 399.2 [M+H]\

Example 15: S-[4-(3-Hydroxy-5-methoxyphenyl-1-yl)-aminoquinazolin-6- yl]-S-methylsulphoximide

Intermediate 15a) :

N-(3-Methoxy-5-hydroxyphenyl)-6-methylsulphanylquinazolin-4-amine

A solution of 210 mg of 4-chloro-6-methylsulphanylquinazoline (J. Med. Chem. 26, (1983), 420 ff.; J. Med. Chem. 37, (1994), 2106 ff.) and 278 mg of 5- amino-3-methoxyphenol in 15 ml of acetonitrile were stirred at 110⁰C for 48 hours. Cooling was followed by dilution with ethyl acetate and removal of the resulting precipitate by filtration. The precipitate was washed with ethyl acetate and dried in vacuo. 333 mg of the title compound were obtained in the form of the hydrochloride.

¹H-NMR (DMSO-d6): δ = 2.70 (s, 3H); 6.35 (t, 1H); 6.74-6.80 (m, 2H); 7.88 (d, 1 H); 7.98 (dd, 1 H); 8.56 (d, 1 H); 8.87 (s, 1 H); 9.84 (s, 1 H); 11.48 (s, 1 H); Intermediate 15b) : N-(3-Methoxy-5-hydroxy-phenyl)-6-methylsulphinyl- quinazolin-4-amine

A solution of 455 mg of sodium periodate in 9 ml of water was added dropwise to a solution of 333 mg of N-(3-methoxy-5-hydroxyphenyl)-6-methylsulphanyl- quinazoline-4-amine in 18 ml of THF at RT. After 40 h, a further 445 mg of sodium periodate in 9 ml of water were added, and the mixture was stirred for 24 h. Ethyl acetate was added until two phases clearly separated from one another. The organic phase was separated and the aqueous phase was extracted twice with a 9:1 dichloromethane/isopropanol mixture. The combined organic phases were dried with sodium sulphate and concentrated in vacuo.

¹H-NMR (DMSO-d6): δ = 2.87 (s, 3H); 3.73 (s, 3H); 6.16 (t, 1H); 6.94 (t, 1 H); 7.07 (t, 1H); 7.94 (d, 1 H); 8.11 (dd, 1H); 8.67 (s, 1H); 8.89 (d, 1H); 9.49 (s, 1H); 9.93 (s, 1 H);

Final product: Example 15: S-[4-(3-Hydroxy-5-methoxyphenyl-1 -yl)- aminoquinazolin-6-yl]-S-methylsulphoximide

12 μl of oleum (20%) were added to a solution of 14.43 mg of N-(3-methoxy-5- hydroxyphenyl)-6-methylsulphinylquinazoline-4-amine in 200 μl of chloroform and the internal temperature was controlled to about 50° C. 3.19 mg of sodium azide were added thereto. After about 3 hours, the mixture was added to ice-water and cautiously adjusted to pH = 11 with sodium hydroxide solution. The organic phase was separated and the aqueous phase was extracted 3 times more with dichloromethane. The combined organic phases were dried with sodium sulphate and concentrated in vacuo. The title compound was obtained after column chromatography (silica gel, hexane/ethyl acetate/2-propanol).

¹H-NMR (DMSO-d6): δ = 3.20 (s, 3H); 4.42 (s, 1 H); 6.17 (t, 1H); 6.93 (t, 1 H); 7.04 (t, 1 H); 7.91 (d, 1H); 8.28 (dd, 1H); 8.68 (s, 1 H); 9.22 (d, 1 H); 9.56 (s, 1H); 10.13 (s, 1 H);

The following were prepared in an analogous manner:

Example 16:

S-[4-(3-Hydroxyphenyl-1-yl)-aminoquinazolin-6-yl]-S-

methylsulphoximide

The title compound was prepared starting from 4-chloro-6- methylsulphanylquinazoline and 3-aminophenol via the intermediates N-(3- hydroxyphenyl)-6-methylsulphanylquinazoline-4-amineN-(3-hydroxyphenyl)-6- methylsulphinylquinazoline-4-amine.

¹H-NMR (DMSO-d6): δ = 3.18 (s, 3H); 4.39 (s, 1 H); 6.49-6.60 (m, 1 H); 7.09-7.22 (m, 2H); 7.30 (s, 1 H); 7.87 (d, 1 H); 8.25 (dd, 1 H); 8.60 (s, 1 H); 9.17 (s, 1H); 10.17 (bs, 1H);

Example 17:

S-[4-(3-Hydroxy-6-methylphenyl-1-yl)-aminoquinazolin-6-yl]-S- methylsulphoximide

The title compound was prepared starting from 4-chloro-6- methylsulphanylquinazoline and 3-amino-4-methylphenol via the intermediates N-(3-hydroxy-6-methylphenyl)-6-methylsulphanylquinazoline-4- amine N-(3-hydroxy-6-methylphenyl)-6-methylsulphinylquinazoline-4-amine.

¹H-NMR (DMSO-d6): δ = 3.19 (s, 3H); 4.37 (s, 1H); 6.63 (d, 1H); 6.69 (d, 1H); 7.07 (d, 1 H); 7.86 (d, 1 H); 8.24 (d, 1 H); 8.46 (s, 1H); 9.10 (s, 1 H); 9.31 (s, 1H); 10.14 (s, 1 H);

Example 18:

S-[4-(3-Hydroxy-6-methylphenyl-1-yl)-aminoquinazolin-6-yl]-S- methylsulphoximide

The title compound was prepared starting from 4-chloro-6- methylsulphanyiquinazoline and 5-amino-2-chlorophenol via the intermediates N-(4-chloro-3-hydroxyphenyl)-6-methylsulphanylquinazoline-4-amine N-(4- chloro-3-hydroxyphenyl)-6-methylsulphinylquinazoline-4-amine.

¹H-NMR (DMSO-d6): δ = 3.19 [s, 3H); 4,43 (s, 1H); 7.27 (dd, 1H); 7.34 (d, 1H); 7.63 (d, 1 H); 7.93 (d, 1H); 8.30 (dd, 1H); 8.69 (s, 1 H); 9.21 (d, 1 H); 10.26 (s, 2H);

BIOLOGICAL ASSAYS OF THE COMPOUNDS OF THE RELEVANT INVENTION ASSAY SYSTEM FOR EphB4 HTRF assay:

A mixture of 20 ng/ml recombinanter EphB4 kinase (ProQinase GmbH, Freiburg, Germany), 2.67 μg/ml polyG Iu AIaTy r, 2 μM ATP, 25 mM HEPES (pH 7.3), 5 mM MgCl₂, 1 mM MnCl₂, 2 mM DTT, 0.1 mM NaVO₄, 1% (v/v) glycerol, 0.02% NP40, EDTA-free protease inhibitors (Complete from Roche, 1 tablet in 50 ml) is incubated at 20°C for 10 min. Test substances are dissolved in 100% DMSO and introduced in 0.017 times the volume before the start of the reaction. 60 minutes after addition of 1.7 times the volume of a solution of 5OmM Hepes pH 7.0, 0.2% BSA, 0.14 μg/ml PT66-Europium, 3.84 μg/ml SA-XL665, 75 mM EDTA, the mixture is measured in a Perkin-Elmer Discovery HTRF measuring instrument.

Cascade assay:

The potency of the compounds according to the invention is estimated in an in vitro inhibition assay. The EphB4 kinase-mediated phosphorylation of a suitable peptide substrate is associated with a consumption of ATP and a corresponding increase in ADP. ADP is detected in a coupled enzymatic reaction with NADH consumption (pyruvate kinase/ lactate dehydrogenase reaction; PK/ LDH). The intrinsic fluorescence of NADH serves as sensitive assay reading signal. The NADH consumption (decrease in the fluorescence intensity) is directly proportional to the EphB4 enzymic activity. The effective concentration of a test compound at which half the enzyme is inhibited (50% signal intensity of the fluorescent light) is indicated as the IC₅₀.

Enzyme (5 nM EphB4, from Millipore, Heidelberg; 0.5 U/ml PK/LDH, from Roche, Mannheim) and substrate (0.1 mg/ml polyGluAlaTyr; 100 μM ATP, 50 μM NADH, 1 mM PEP) are incubated in the presence and absence of the test substance (dilutions in DMSO) in an assay volume of a total of 42 μl of assay buffer (50 mM MOPS pH 7.0, 5 mM MgCl₂, 0.3 mM ZnCl₂, 2.5 mM EDTA, 1 mM DTE, 0.01% w/v BSA, 0.006 % v/v Igepal, 0.001 % w/v histone) in a 384-well microtitre plate at 32⁰C for two hours. The intensity of the fluorescent light from the assay mixtures is measued (Tecan Safire, Ex/Em. 340/465 nm, TECAN, Crailsheim). The IC_5O values are estimated by plotting the intensity of the fluorescent light against the active substance concentration.

Inhibition of EphB4 autophosphorylation in CHO-EphB4 cells:

Binding of the ligand EphrinB2 as dimer (ephrinB2-Fc) to the EphB4 receptor leads to activation and autophosphorylation of the receptor. This autophosphorylation can be inhibited by EphB4 kinase inhibitors. The phosphorylated form of the receptor, which contains a c-Myc sequence, can be detected in a Sandwich Elisa. EphB4 kinase inhibitors reduce dose- dependently the amount of the phosphorylated EphB4 receptor. 80 000 stably transfected CHO-EphB4 cells/well are seeded in a 96-well cell culture plate and cultured in DMEM/HAMS-F12/10% FCS at 37°C and 5% CO2 overnight (Sturz A. et al. 2004, Biochem. Biophys. Acta 313, 80-88, modified). The cells are then washed once with PBS, pretreated with substances in serum-free medium for 10 min and then incubated with 0.5μg/ml (up to 1 μg/ml) ephrinB2-Fc at 4°C for 60 min. After the treatment, the cells are lysed in 100 μl/well lysis buffer (5OmM HEPES pH 7.2, 15OmM NaCl, 1mM MgCl2, 1OmM Na4P2O7, 10OmM NaF, 10% glycerol (v/v), 1.5% Triton X-100, 2mM orthovanadates (pH 7.4), with complete protease inhibitors (Roche) and phosphatase inhibitor cocktail Il (Sigma)) and incubated for 30 min. Autophosphorylated EphB4 receptor is detected in a Sandwich ELISA with anti- c-Myc and anti-phosphotyrosine-HRP antibodies. For this purpose, 96-well plates (Lumitrac 600, Greiner) are incubated with 100 μl/well anti-c-myc antibody (5μg/ml; Roche) at 4° C overnight, then blocked with 250 μl/well 5% Prionex (Calbiochem) at RT for 3 hours and subsequently incubated with 100 μl of cell lysate at 4° C overnight. The ELISA plates are then washed twice with PBS and incubated with 100 μl/well anti-phospho-Tyr-HRP (1 :10 000 in lysis buffer) at 4° C overnight. The plates are then washed three times with PBS, 100 μl/well BM chemiluminescence ELISA substrate POD (Roche) are added, and the luminescence is measured in a luminometer (LumiCount, Packard or Lumibox, Bayer). BIOLOGY

Compounds of the relevant invention have surprising inhibitory activity on EphB4 with IC50 values of less than 10 μM in at least one of the abovementioned assay systems.

Claims

1. Quinoline and quinazoline derivatives having the general formula (I) :

(I) in which:

W is equal to CH or N; Y is equal to NR¹R² or OR¹;

R¹ and R² are identical or different and are selected one or more times independently of one another from the group comprising hydrogen, -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-Ci₀- cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C₆-Ci₂-aryl, -C₅-C₁₈- heteroaryl, -d-C_ό-alkyl-CrCβ-alkoxy, -CrC₆-alkyl-Ci-C₆-alkoxy-

C_rC₆-alkoxy, -(CH₂)_n-C₆-Ci₂-aryl, -(CH₂)_n-C₅-Ci₈-heteroaryl, -(CH₂)_n-C₃-Cio-cycloalkyl, -(CH₂)_n-C₃-C₁₂-heterocycloalkyl,

-phenylene-(CH₂)_p-R⁶, -(CH₂)_PPO₃(R⁶)₂, -(CH₂)_P-NR⁴C(=S)R⁵, -(CH₂)_p-NR⁴S(=O)R⁵, -(CH₂)_P-NR⁴C(=O)NR⁵R⁶, -(CH₂)_P-NR⁴C(=O)OR⁵, -(CH₂)_P-NR⁴C(=NH)NR⁵R⁶, -(CH₂)_P-NR⁴C(=S)NR⁵R⁶, -(CH₂)_P-

NR⁴S(=O)NR⁵R⁶, -(CH₂)p-NR⁴S(=O)₂NR⁵R⁶, -(CH₂)_P-C(=O)R⁵, -(CH₂)_P- C(=S)R⁵, -(CH₂)p-S(=O)R⁵, -(CH₂)_P-S(O)(NH)R⁵, -(CH₂)_P-S(O)₂R⁵, -(CH₂)P-SO₂OR⁵, -(CH₂)_P-CO₂R⁵, -(CH₂)_P-CSNR⁵R⁶, -CHR⁵R⁶ and -(CH₂)_P-SR⁵ where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃- Cio-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C₆-Ci₂-aryl, -C₅-C₁₈- heteroaryl or -Ci-C_δ-alkoxy are unsubstituted or are substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, -NR⁵R⁶, -C(O)NR⁵R⁶, -S(O)₂NR⁵R⁶, -NR⁵S(O)₂R⁶, -NR⁵C(O)R⁶, -SR⁵ , -R⁵, or -OR⁵, where the carbon framework of the -C₃-Ci₀-cycloalkyl and of the -C_rCio-alkyl may comprise one or more times independently of one another nitrogen, oxygen, sulphur atoms, -NR⁴ or C=O groups or one or more double bonds, or R¹ and R² optionally form together a bridge of 3-10 methylene units, where up to two methylene units are optionally replaced by O, S or -NR⁴, and where the phenyl radical is optionally substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, -NR⁵R⁶, alkyl or -OR⁵; in which R¹ is not hydrogen when Y is NR¹R² and R² is hydrogen; and in which R¹ is not hydrogen when Y is OR¹;

R³ is selected from the group comprising hydrogen, -Ci-C₆-alkyl,

-C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -C₆-Ci₂-aryl, -Cs-Cis-heteroaryl, C(=O)R⁵, C(=O)NR⁵R⁶ or C(=O)OR⁵, where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂- C₆-alkynyl, -C₃-Cio-cycloalkyl, -Ca-drheterocycloalkyl, -C₆-Ci₂- aryl or -Cs-C^-heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵, C(=O)NR⁵R⁶, C(=O)OR⁵, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵, R⁴ is selected from the group comprising -C_rC₆-alkyl, -C₂-C₆- alkenyl, -C₂-C₆-alkynyl, -C₃-Cio-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -C₆-C₁₂-aryl, -Cs-Cis-heteroaryl, C(O)R⁵, C(=O)NR⁵R⁶ or C(=O)OR⁵, where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂- C_δ-alkynyl, -CrCio-cycloalkyl, -C₃-Ci₂-heterocycloalkyl , -C₆-Ci₂- aryl or -C₅-Ci₈-heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵, C(=O)OR⁵, C(=O)NR⁵R⁶, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵, or R³ and R⁴ may, via the respective nitrogen atom and the respective sulphur atom to which they are attached, form a ring having a ring size of from 5 to 10 ring atoms, optionally consisting of carbon, nitrogen, oxygen or sulphur atoms; R⁵ and R⁶ are identical or different and selected independently of one another from the group comprising hydrogen, -Ci-Cio-alkyl, -C₂- C₁₀-alkenyl, -C₂-Ci₀-alkynyl, -CrC₆-alkoxy, -C₃-Ci₀-cycloalkyl, -C₃- C₁₂-heterocycloalkyl, -C₆-C₁₂-aryl and -C₅-C₁₈-heteroaryl, where -CrCio-alkyl, -C₂-Ci₀-alkenyl, -C₂-Ci₀-alkynyl, -C_rC₆-alkoxy, -C₃-

Cio-cycloalkyl, -CrCirheterocycloalkyl, -C₆-Ci₂-aryl or -C₅-C₁₈- heteroaryl are unsubstituted or one or more times independently of one another by hydroxy, halogen, cyano, nitro, -OR⁷, -NR⁷R⁸, -C(O)NR⁷R⁸, -C(O)OR⁷ or -C_rC₆-alkyl, where -C_rC₆-alkyl is unsubstituted or one or more times independently of one another by halogen, hydroxy, cyano, -NR⁷R⁸, -OR⁷ or phenyl; or R⁵ and R⁶ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by 0, S or NR⁴; R⁷, R⁸ are identical or different and selected independently of one another from the group comprising hydrogen, -C_rC₄-alkyl, -C₅- Cis-aryl and -Cs-Ciβ-heteroaryl, where -CrC₄-alkyl, -C₆-Ci₂-aryl, -C₅-Ci₈-heteroaryl is unsubstituted or one or more times independently of one another by halogen or alkoxy, or R⁷ and R⁸ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by O, S or -NR⁴; n = 1 , 2, 3, 4, 5, or 6, p = 0, 1 , 2, 3, 4, 5, or 6, and

the N-oxides, solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts thereof.

2. Quinoline and quinazoline derivatives of the general formula (I) according to Claim 1, in which:

W is equal to CH or N;

Y is equal to NR¹R² or OR¹; R¹ is selected one or more times independently of one another from the group comprising -Ci-C₆-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-C₁₀-cycloalkyl, -CrCirheterocycloalkyl, -C₆-Ci₂-aryl, -C₅-Ci₈- heteroaryl, -Ci -C₆-alkyl-Ci -Cβ-alkoxy, -Ci -C₆-alkyl-Ci -C₆-alkoxy- Ci-C₆-alkoxy, -(CH₂)n-C₆-Ci₂-aryl, -(CH₂)_n-C₅-Ci₈-heteroaryl,

-(CH₂)_n-C₃-Cio-cycloalkyl, -(CH₂)_n-C₃-C₁₂-heterocycloalkyl,

-phenylene-(CH₂)_p-R⁶, -(CH₂)_PPO₃(R⁶)₂, -(CH₂)_P-NR⁴C(=S)R⁵, -(CH₂)_P-NR⁴S(=O)R⁵, -(CH₂)_P-NR⁴C(=O)NR⁵R⁶, -(CH₂)_P-NR⁴C(=O)OR⁵, -(CH₂)_P-NR⁴C(=NH)NR⁵R⁶, -(CH₂)_P-NR⁴C(=S)NR⁵R⁶, -(CH₂)_P- NR⁴S(=O)NR⁵R⁶, -(CH₂)_P-NR⁴S(=O)₂NR⁵R⁶, -(CH₂)_P-C(=O)R⁵, -(CH₂)_P-

C(=S)R⁵, -(CH₂)_P-S(=O)R⁵, -(CH₂)_P-S(O)(NH)R⁵, -(CH₂)_P-S(O)₂R⁵, -(CH₂)_P-SO₂OR⁵, -(CH₂)_P-CO₂R⁵, -(CH₂)_P-CSNR⁵R⁶, -CHR⁵R⁶ and -(CH₂)_P-SR⁵; where -CrC_δ-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -Crdrheterocycloalkyl, -C₆-Ci₂-aryl, -C₅-Ci₈- heteroaryl or -CrC_ό-alkoxy is unsubstituted or is substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, -NR⁵R⁶, -C(O)NR⁵R⁶, -S(O)₂NR⁵R⁶, -NR⁵S(O)₂R⁶, -NR⁵C(O)R⁶, -SR⁵ , -R⁵, or -OR⁵, where the carbon framework of the -C₃-Ci₀-cycloalkyl and of the -C_rCio-alkyl may comprise one or more times independently of one another nitrogen, oxygen, sulphur atoms, -NR⁴ or C=O groups or one or more double bonds,

R² is selected one or more times independently of one another from the group comprising hydrogen, -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂- Cβ-alkynyl, -C₃-Cio-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -(CH₂J_n-

C₃-Cio-cycloalkyl, -(CH₂)_n-C₃-Ci₂-heterocycloalkyl, and

-phenylene-(CH₂)_p-R⁶, where -CrC_ό-alkyl, -C₂-C₆-alkenyl, -C₂-C₆- alkynyl, -C₃-C₁₀-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C₆-Ci₂-aryl or -C₅-Cis-heteroaryl is unsubstituted, where the carbon framework of the -C₃-C₁₀-cycloalkyl and of the -CrCio-alkyl may comprise one or more times independently of one another nitrogen, oxygen, sulphur atoms, -NR⁴ or C=O groups or one or more double bonds; or :

R¹ and R² optionally together form a bridge of 3-10 methylene units, where up to two methylene units are optionally replaced by O, S or

-NR⁴, and where the phenyl radical is optionally substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, -NR⁵R⁶, alkyl or -OR⁵;

R³ is selected from the group comprising hydrogen, -CrC₆-alkyl,

-C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -C₆-Ci₂-aryl, -C₅-Ci₈-heteroaryl, C(=O)R⁵, C(=O)NR⁵R⁶ or C(=O)OR⁵, where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂-

C_δ-alkynyl, -C₃-Cio-cycloalkyl, -C₃-Ci₂-heterocycloalkyl , -Ce-C₁₂- aryl or -Cs-Cis-heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵, C(=O)NR⁵R⁶, C(=O)OR⁵, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵,

R⁴ is selected from the group comprising -d-C_ό-alkyl, -C₂-C₆- alkenyl, -C₂-C₆-alkynyl, -C₃-Cio-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -C₆-Ci₂-aryl, -C₅-Ci₈-heteroaryl, C(=O)R⁵, C(=O)NR⁵R⁶ or C(=O)OR⁵, where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂- C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -C₃-Ci₂-heterocycloalkyl , -C₆-Ci₂- aryl or -C₅-Ci₈-heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵, C(=O)OR⁵, C(O)NR⁵R⁶, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵, R⁵ and R⁶ are identical or different and are selected independently of one another from the group comprising hydrogen, -CrCio-alkyl, -C₂- Cio-alkenyl, -C₂-Ci₀-alkynyl, -Ci-C₆-alkoxy, -C₃-Ci₀-cycloalkyl, -C₃- Cirheterocycloalkyl, -C₆-Ci₂-aryl and -C₅-Ci₈-heteroaryl, where -CrCio-alkyl, -C₂-Ci₀-alkenyl, -C₂-C₁₀-alkynyl, -d-C₆-alkoxy, -C₃- Cio-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -Cβ-C₁₂-aryl or -C₅-C₁₈- heteroaryl are unsubstituted or one or more times independently of one another by hydroxy, halogen, cyano, nitro, -OR⁷, -NR⁷R⁸, -C(O)NR⁷R⁸, -C(O)OR⁷ or -C_rC₆-alkyl, where -C_rC₆-alkyl is unsubstituted or one or more times independently of one another by halogen, hydroxy, cyano, -NR⁷R⁸, -OR⁷ or phenyl; or R⁵ and R⁶ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by O, S or NR⁴;

R⁷, R⁸ are identical or different and independently of one another selected from the group comprising hydrogen, -CrC₄-alkyl, -C₅- Ci₈-aryl and -Cs-Ciβ-heteroaryl, where -C_rC₄-alkyl, -C₆-Ci₂-aryl, -Cs-da-heteroaryl is unsubstituted or one or more times independently of one another by halogen or alkoxy, or R⁷ and R⁸ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by O, S or -NR⁴; n = 1 , 2, 3, 4, 5, or 6, p = 0, 1 , 2, 3, 4, 5, or 6, and

the N-oxides, solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts thereof.

3. Quinoline and quinazoline derivatives of the general formula (I) according to Claim 1 or 2, in which:

W is equal to CH or N;

Y is equal to NR¹R² or OR¹; R¹ is selected one or more times independently of one another from the group comprising -CrCβ-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-Cio-cycloalkyl, -C₃-C₁₂-heterocycloalkyl, -C₆-Ci₂-aryl, -C₅-Ci₈- heteroaryl, -Ci -C₆-alkyl-Ci -C₆-alkoxy, -Ci -C_δ-alkyl-Ci -Cβ-alkoxy- d-C₆-alkoxy, -(CH₂)_n-C₆-Ci2-aryl, -(CH₂)_n-C₅-Ci₈-heteroaryl, -(CH₂)_n-C₃-Cio-cycloalkyl, -(CH₂)_n-C₃-Ci₂-heterocycloalkyl,

-phenylene-(CH₂)_p-R⁶, -(CH₂)_PPO₃(R⁶)₂, -(CH₂)_P-NR⁴C(=S)R⁵, -(CH₂)p-NR⁴S(=O)R⁵, -(CH₂)_p-NR⁴C(=O)NR⁵R⁶, -(CH₂)_P-NR⁴C(=O)OR⁵, -(CH₂)_P-NR⁴C(=NH)NR⁵R⁶, -(CH₂)_P-NR⁴C(=S)NR⁵R⁶, -(CH₂)_P- NR⁴S(=O)NR⁵R⁶, -(CH₂)_p-NR⁴S(=O)₂NR⁵R⁶, -(CH₂)_P-C(=O)R⁵, -(CH₂)_P- C(=S)R⁵, -(CH₂)_p-S(=O)R⁵, -(CH₂)_P-S(O)(NH)R⁵, -(CH₂)_P-S(O)₂R⁵, -(CH₂)_P-SO₂OR⁵, -(CH₂)_P-CO₂R⁵, -(CH₂)_P-CSNR⁵R⁶, -CHR⁵R⁶ and -(CH₂J_p-SR⁵; where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -C₃-C₁₂-heterocycloalkyl, -C₆-Ci₂-aryl, -C₅-Ci₈- heteroaryl or -C_rC₆-alkoxy is unsubstituted or is substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, -NR⁵R⁶, -C(O)NR⁵R⁶, -S(O)₂NR⁵R⁶, -NR⁵S(O)₂R⁶, -NR⁵C(O)R⁶, -SR⁵ , -R⁵, or -OR⁵, where the carbon framework of the -C₃-C₁₀-cycloalkyl and of the -CrCio-alkyl may comprise one or more times independently of one another nitrogen, oxygen, sulphur atoms, -NR⁴ or C=O groups, or one or more double bonds,

R² is selected one or more times independently of one another from the group comprising hydrogen, or -C_rC₆-alkyl;

R³ is selected from the group comprising hydrogen, -CrC₆-alkyl,

-C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -C₆-Ci₂-aryl, -Cs-Ciβ-heteroaryl, C(=O)R⁵, Q=O)NR⁵R⁶ or C(=O)OR⁵, where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂- C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -C₃-Ci ₂-heterocycloalkyl, -C₆-Ci₂- aryl or -C₅-Ci₈-heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵, C(=O)NR⁵R⁶, C(=O)OR⁵, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵, R⁴ is selected from the group comprising -Ci-C₆-alkyl, -C₂-C₆- alkenyl, -C₂-C₆-alkynyl, -C₃-Cio-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -C₆-Ci₂-aryl, -Cs-Cis-heteroaryl, C(=O)R⁵, C(=O)NR⁵R⁶ or C(=O)OR⁵, where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂- C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C₆-Ci₂- aryl or -Cs-Ciβ-heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵, C(=O)OR⁵, C(=O)NR⁵R⁶, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵, R⁵ and R⁶ are identical or different and selected independently of one another from the group comprising hydrogen, -C_rCio-alkyl, -C₂- Cio-alkenyl, -C₂-C₁₀-alkynyl, -CrC₆-alkoxy, -C₃-Ci₀-cycloalkyl, -C₃- C₁₂-heterocycloalkyl, -Cβ-C₁₂-aryl and -Cs-Ciβ-heteroaryl, where -d-Cio-alkyl, -C₂-Ci₀-alkenyl, -C₂-C₁₀-alkynyl, -CrC₆-alkoxy, -C₃- do-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C₆-Ci₂-aryl or -C₅-C₁₈- heteroaryl are unsubstituted or one or more times independently of one another by hydroxy, halogen, cyano, nitro, -OR⁷, -NR⁷R⁸, -C(O)NR⁷R⁸, -C(O)OR⁷ or -C_rC₆-alkyl, where -C_rC₆-alkyl is unsubstituted or one or more times independently of one another by halogen, hydroxy, cyano, -NR⁷R⁸, -OR⁷ or phenyl; or R⁵ and R⁶ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by O, S or NR⁴; R⁷, R⁸ are identical or different and selected independently of one another from the group comprising hydrogen, -CrC₄-alkyl, -C₅- dβ-aryl and -Cs-Cis-heteroaryl, where -Ci-C₄-alkyl, -C₆-Ci₂-aryl, -C₅-Ci₈-heteroaryl is unsubstituted or one or more times independently of one another by halogen or alkoxy, or R⁷ and R⁸ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by O, S or -NR⁴; n = 1 , 2, 3, 4, 5, or 6, p = 0, 1 , 2, 3, 4, 5, or 6, and

the N-oxides, solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts thereof.

4. Quinoline and quinazoline derivatives of the general formula (I) according to any of Claims 1 , 2 or 3, in which:

W is equal to CH or N;

Y is equal to NR¹R² or OR¹; R¹ is selected one or more times independently of one another from the group comprising -Ci-C₆-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C₆-Ci₂-aryl, -C₅-Ci₈- heteroaryl, -Ci -C₆-alkyl-Ci -C₆-alkoxy, -Ci -C₆-alkyl-Ci -C₆-alkoxy- Ci-C₆-alkoxy, -(CH₂)_n-C₆-Ci₂-aryl, -(CH₂)n-C₅-Ci₈-heteroaryl,

-(CH₂)n-C₃-Cio-cycloalkyl, -(CH₂)n-C₃-C₁₂-heterocycloalkyl,

-phenylene-(CH₂)p-R⁶, -(CH₂)pPO₃(R⁶)2, -(CH₂)_P-NR⁴C(=S)R⁵, -(CH₂)_p-NR⁴S(=O)R⁵, -(CH₂)p-NR⁴C(=O)NR⁵R⁶, -(CH₂)_P-NR⁴C(=O)OR⁵, -(CH₂)_P-NR⁴C(=NH)NR⁵R⁶, -(CH₂)_P-NR⁴C(=S)NR⁵R⁶, -(CH₂)_P- NR⁴S(=O)NR⁵R⁶, -(CH₂)_P-NR⁴S(=O)₂NR⁵R⁶, -(CH₂)_P-C(=O)R⁵, -(CH₂)_P-

C(=S)R⁵, -(CH₂)p-S(=O)R⁵, -(CH₂)_P-S(O)(NH)R⁵, -(CH₂Jp-S(O)₂R⁵, -(CH₂)_p-SO₂OR⁵, -(CH₂)p-CO₂R⁵, -(CH₂)_P-CSNR⁵R⁶, -CHR⁵R⁶ and -(CH₂J_p-SR⁵; where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-Cio-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C₆-Ci₂-aryl, -C₅-Ci₈- heteroaryl or -CrC₆-alkoxy is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, -NR⁵R⁶, -C(O)NR⁵R⁶, -S(O)₂NR⁵R⁶, -NR⁵S(O)₂R⁶, -NR⁵C(O)R⁶, -SR⁵ , -R⁵, or -OR⁵, where the carbon framework of the -C₃-Cio-cycloalkyl and of the -Ci-Cio-alkyl may comprise one or more times independently of one another nitrogen, oxygen, sulphur atoms, -NR⁴ or C=O groups or one or more double bonds, R² is selected one or more times independently of one another from the group comprising hydrogen, or -Ci-C₆-alkyl; R³ is selected from the group comprising hydrogen, -CrC₆-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -Cs-Cio-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -C₆-Ci₂-aryl, -C₅-Ci₈-heteroaryl, C(=O)R⁵, C(=O)NR⁵R⁶ or C(=O)OR⁵, where -C_rC₆-alkyl, -C₂-C₆-alkenyl, -C₂- C_ό-alkynyl, -CrCio-cycloalkyl, -C₃-Ci₂-heterocycloalkyl , -CO-C_I2- aryl or -C₅-Ci₈-heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵, C(=O)NR⁵R⁶, C(=O)OR⁵, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵, R⁴ is selected from the group comprising -CrC₆-alkyl, -C₂-C₆- alkenyl, -C₂-C₆-alkynyl, -C₃-Ci₀-cycloalkyl, -C₃-Ci₂- heterocycloalkyl, -C₆-Ci₂-aryl, or -C₅-Ci₈-heteroaryl, where -C_r C₆-alkyl, -C₂-C₆-alkenyl, -C₂-C₆-alkynyl, -C₃-C₁₀-cycloalkyl, -C₃- Cu-heterocycloalkyl, -C₆-Ci₂-aryl or -C₅-Ci₈-heteroaryl is unsubstituted or substituted one or more times independently of one another by hydroxy, halogen, nitro, cyano, phenyl, C(=O)R⁵, Q=O)OR⁵, C(=O)NR⁵R⁶, -NR⁵R⁶, alkyl, -SR⁵ or -OR⁵,

R⁵ and R⁶ are identical or different and independently of one another selected from the group comprising hydrogen, -CrCio-alkyl, -C₂-

Qo-alkenyl, -C₂-Cio-alkynyl, -CrCβ-alkoxy, -C₃-Cio-cycloalkyl, -C₃-

Ci₂-heterocycloalkyl, -C₆-Ci₂-aryl and -Cs-C^-heteroaryl, where

-CrC₁₀-alkyl, -C₂-C₁₀-alkenyl, -C₂-Ci₀-alkynyl, -C_rC₆-alkoxy, -C₃-

Cio-cycloalkyl, -C₃-Ci₂-heterocycloalkyl, -C₆-C₁₂-aryl or -Cs-Qe- heteroaryl are unsubstituted or one or more times independently of one another by hydroxy, halogen, cyano, nitro, -OR⁷, -NR⁷R⁸,

-C(O)NR⁷R⁸, -C(O)OR⁷ or -C_rC₆-alkyl, where -C_rC₆-alkyl is unsubstituted or one or more times independently of another by halogen, hydroxy, cyano, -NR⁷R⁸, -OR⁷ or phenyl; or R⁵ and R⁶ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by O, S or

NR⁴;

R⁷, R⁸ are identical or different and independently of one another selected from the group comprising hydrogen, -CrC₄-alkyl, -C₅- Cie-aryl and -Cs-Cie-heteroaryl, where -C|-C₄-alkyl, -C₆-Ci₂-aryl,

-C₅-Ci₈-heteroaryl is unsubstituted or one or more times independently of one another by halogen or alkoxy, or R⁷ and R⁸ optionally together form a bridge of 3-10 methylene units, where up to two methylene units may optionally be replaced by O, S or -NR⁴; n = 1 , 2, 3, 4, 5, or 6, p = 0, 1 , 2, 3, 4, 5, or 6, and the N -oxides, solvates, hydrates, stereoisomers, diastereomers, enantiomers and salts thereof.

5. Quinoline and quinazoline derivatives having the general formula (I) according to any of Claims 1 to 4, which is selected from:

S-[4-(3-hydroxyphenyl-1 -yl)-aminoquinolin-6-yl]-S-methylsulphoximide; S-[4-

(3-hydroxy-6-methyl-phenyl-1 -yl)-aminoquinolin-6-yl]-S-methylsulphoximide;

S-[4-(3-hydroxy-5-methoxy-phenyl-1 -yl)-aminoquinolin-6-yl]-S- methylsulphoximide; S-[4-(6-chloro-3-hydroxyphenyl-1 -yl)-aminoquinolin-6- yl]-S-methylsulphoximide; S-[4-(3-hydroxy-5-methoxy-phenyl-1 -yl)- hydroxyquinolin-6-yl]-S-methylsulphoximide; N,S-dimethyl-S-[4-(3- hydroxyphenyl-1 -yl)-aminoquinolin-6-yl]-sulphoximide; N,S-dimethyl-S-[4-(3- hydroxy-6-methyl-phenyl-1 -yl)-aminoquinolin-6-yl]-sulphoximide; N, S- dimethyl-S-[4-(3-hydroxy-5-methoxyphenyl-1 -yl)-aminoquinolin-6-yl]- sulphoximide; N-acetyl-S-[4-(3-hydroxy-5-methoxyphenyl-1-yl)-aminoquinolin- 6-yl]-S-methylsulphoximide; N-acetyl-S-[4-(3-hydroxy-6-methylphenyl-1 -yl)- aminoquinolin-6-yl]-S-methylsulphoximide;

S-[4-(3-hydroxy-6-methylphenyl-1 -yl)-aminoquinolin-6-yl]-N-methoxy- carbonyl-S-methylsulphoximide;

S-[4-(3-hydroxy-5-methoxyphenyl-1-yl)-aminoquinolin-6-yl]-N- methoxycarbonyl-S-methylsulphoximide;

N-(ethylamino)carbonyl-S-[4-(3-hydroxy-5-methoxyphenyl-1 -yl)aminoquinolin- 6-yl]-S-methylsulphoximide;

N-(ethylamino)carbonyl-S-[4-(3-hydroxy-6-methylphenyl-1 -yl)aminoquinolin-6- yl]-S-methylsulphoximide;

S-[4-(3-hydroxy-5-methoxyphenyl-1 -yl)aminoquinazolin-6-yl]-S- methylsulphoximide; S-[4-(3-hydroxyphenyl-1 -yl)aminoquinazolin-6-yl]-S-methylsulphoximide;

S-[4-(3-hydroxy-6-methylphenyl-1 -yl)aminoquinazolin-6-yl]-S- methylsulphoximide; and

S-[4-(3-hydroxy-6-methylphenyl-1 -yl)aminoquinazolin-6-yl]-S- methylsulphoximide;

6. Process for preparing the quinoline or quinazoline derivative according to any of Claims 1 to 5, where an intermediate of the general formula (II) :

(II)

in which:

W, R³ and R⁴ are as defined in any of Claims 1 to 4;

X is a halogen, an -OS(=O)2R⁹ group, an -OS(=O)2C_xF_2x+i group, an -OP(=O)(OR⁹)₂ group or an -(NR⁹R¹⁰R¹¹J⁺-Z^" group;

R⁹, R¹⁰, R¹¹ is independently of one another a CrCβ-alkyl group or C₆-C₁₂-aryl group;

Z is an anion such as a halide; and x is 1 , 2, 3, 4, or 5;

is reacted with a reagent of the general formula (A) :

HY

(A), in which Y is defined as in any of Claims 1 to 4,

to give a compound of the general formula (I) :

(I)

in which W, R³, R⁴ and Y are as defined in any of Claims 1 to 4.

7. Use of the quinoline or quinazoline derivative according to any of Claims 1 to 5, or as can be prepared according to Claim 6, for producing a medicament.

8. Use of the quinoline or quinazoline derivative according to any of Claims 1 to 5, or as can be prepared according to Claim 6, for producing a medicament for the treatment of disorders in which angiogenesis, lymphangiogenesis or vasculogenesis are involved, of disorders of the blood vessels, of disorders caused by hyperproliferation of body cells, and of chronic or acute neurodegenerative disorders.

9. Use of the quinoline or quinazoline derivative according to any of Claims 1 to 5, or as can be prepared according to Claim 6, for diagnostic purposes in vitro or in vivo for identifying receptors in tissues by means of autoradiography or PET.

10. Use of the quinoline or quinazoline derivative according to any of Claims 1 to 5, or as can be prepared according to Claim 6, as inhibitor of Eph receptor kinases.

11. Use of the quinoline or quinazoline derivative according to any of Claims 1 to 5, or as can be prepared according to Claim 6, in the form of a pharmaceutical product for enteral, parenteral and oral administration.

12. Medicaments which comprise at least one quinoline or quinazoline derivative according to any of Claims 1 to 5, or as can be prepared according to Claim 6, and suitable formulation substances and carriers.

13. Intermediate of the general formula (II) :

(II)

in which:

W, R³ and R⁴ are as defined in any of Claims 1 to 4, and X is a halogen, an OS(=O)₂R⁹ group, an OP(=O)(OR⁹)₂ group or an (NR⁹R¹⁰R¹¹ )\Z^" group, where R⁹, R¹⁰ and R¹¹ is independently of one another a C_rC₆-alkyl group or C₆-Ci₂-aryl group, and Z^" is an anion such as a halide.

14. Use of one of the intermediates of the general formula (II) according to Claims 13, for preparing a quinoline or quinazoline derivative of the general formula (I) according to any of Claims 1 to 5.