MXPA06006593A - Carboxamide derivatives - Google Patents

Abstract

The invention relates to novel compounds of formula (I), wherein:D, E, Q, T, X, Y, Z, Z', R1, R4, and R4'have the meanings cited in Claim 1. These novel compounds are inhibitors of coagulation factor Xa and can be used for the prophylaxis and/or the treatment of thromboembolic diseases and for treating tumors.

Description

CARBOXYLIC ACID AMID DERIVATIVES Description of the invention The invention relates to compounds of the formula I wherein D is an unsubstituted mono- or polysubstituted mono- or polysubstituted carbocycle or heterocycle with Hal, A, OR2, N (R2) 2, N02, CN, COOR2, CON (R) 2 or -C = CH with 0 to 4 N, O and / or S atoms, X is NR3 or O, Y is O, S, NH, N-CN or N-N02, R1 is H, Ar, Het, cycloalkyl or A, which may be mono, di or trisubstituted with OR2, SR2, S (0) fflR2; S02N (R2) 2, S03R2, S (= 0) (= NR2) R2, NR2S02R2, OS02R2, OS02N (R2) 2, N (R2) 2, CN, COOR2, CON (R2) 2, Ar, Het or cycloalkyl , E is CH or N, Z is absent or is a group (CH2) q unsubstituted or unsubstituted with carbonyl oxygen (= 0), where one or two CH2 groups may be replaced by N, 0 and / or S and / or by a group -CH = CH-, Ref. -172735 Z 'is absent or is a group (CH2) g < unsubstituted or monosubstituted with carbonyl oxygen (= 0), wherein one or two CH2 groups may be replaced by N, 0 and / or S atoms and / or by a group - CH = CH-, Q is absent, is 0, NR2, C = 0, S02 or C (R2) n, R2 is H, A, - [C (R3) 2] n-Ar ', - [C (R3) _] nHet', - [C ( R3) 2.n- cycloalkyl, - [C (R3) 2] nN (R3) 2 or - [C (R3) 2] n-0R3, R3 is H or A, R4, R4 'each, independently of each other, is absent, are A, OH or OA, R4 and R4' are also together methylene or ethylene, T is a saturated mono or bicyclic carbocycle or heterocycle , unsaturated or aromatic with 0 to 4 N, 0 and / or S atoms, which may be mono, di or trisubstituted with = 0, = S, = NH, = NR3, = N0R3, = NC0R3, = NC00R3, = N0C0R3, R3, Hal, A, - [C (R3) 2] n- Ar, - [C (R3) 2] n-Het, - [C (R3) 2] n-cycloalkyl, OR3, N (R3 )2. N02, CN, COOR3, CON (R3) 2, NR3C0A, NR3CON (R3) 2, NR3S02A, COR3, S02NR2 and / or S (0) nA, A is unbranched or branched alkyl with 1-10 C atoms, where one or two CH2 groups can be replaced by 0 or S atoms and / or by groups -CH = CH- and / or also 1-7 H atoms can be replaced by F, Ar is unsubstituted phenyl, naphthyl or biphenyl or mono, di or trisubstituted with Hal, A, OR2, N (R) 2 / N02, CN, COOR2, CON (R2) 2, NR2COA, NR2S02A, COR2, S02N (R2) 2, - [C (R3) 2] n-COOR2, -0- [C (R3) 2] or-C00R2, S03H or S (0) nA, Ar 'is phenyl unsubstituted or mono, di or trisubstituted with Hal, A, OR3, N (R3) 2, N02, CN, COOR3, C0N (R3) 2, NR3COA, NR3CON (R3) 2, NR3S02A, COR3, S02N (R3) 2, S (0) nA, -tC (R3) 2Jn-C00R3 or -0- [C (R3) 2] or-C00R3, Het is a saturated or unsaturated mono- or bicyclic heterocycle with 1 to 4 N, O and / or S atoms, which may be unsubstituted or mono, di or trisubstituted with oxygen of carbonyl (= 0), = S, = N (R2) 2, Hal, A, - [C (R3) 2] n-Ar, - [C (R3) 2] n-Het ', - [C ( R3) 2] n-cycloalk ilo, - [C (R3) 2] n-OR2, - [C (R3) 2] n- N (R3) 2, N02, CN, - [C (R3) 2] n-COOR2, - [C ( R3) 2] n-CON (R2) 2, - [C (R3) 2ln-NRCOA, NR2CON (R2) 2, - [C (R3) 2] n-NR2S02A, COR2, S02N (R2) 2 and / or S (0) nA, Het 'is a mono heterocycle or saturated, unsaturated or aromatic bicyclic with 1 to 4 N, 0 and / or S atoms, which may be unsubstituted or mono or disubstituted with carbonyl oxygen, = S, = N (R3), Hal, A, OR3, N (R3) 2, N02, CN, COOR3, CON (R3) 2, NR3COA, NR3CON (R3) 2, NR3S02A, COR3, S02N (R3) 2 and / or S (0) nA, Hal is F, Cl, Br or I, m is 1 or 2, n is 0, 1 or 2, or is 1, 2 or 3, p is 1, 2, 3, 4 or 5, q, q 'are each, independently between yes, 0, 1, 2, 3 or 4, where at least one of the groups Z or Z 'is present, and 0 <; q + q '< 6, as well as their derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions. Also the subject of the invention are optically active forms, racemates, diastereomers, as well as hydrates and solvates, for example, alcoholates, of these compounds. The invention was aimed at finding new compounds with valuable properties, in particular those which can be used for the preparation of medicaments. It was found that the compounds of the formula I and their salts have very valuable pharmacological properties and are well tolerated. In particular, exhibit factor Xa inhibitory properties and, therefore, can be used to combat and prevent thromboembolic conditions such as thrombosis, myocardial infarction, arteriosclerosis, inflammation, stroke, angina pectoris, post-angioplasty restenosis and claudicatio intermittens. The compounds of the formula I according to the invention can also be inhibitors of the factor Vlla coagulation factors, factor IXa and thrombin in the blood coagulation cascade. Other carboxylic acid amides are described in WO 02/48099.; Aromatic amides are described in WO 99/00121 and WO 00/39118. The aromatic amidine derivatives with antithrombotic action are known, eg. ex. , of EP 0 540 051 Bl. Cyclic guanidines for the treatment of thromboembolic disorders are described, eg, in WO 97/08165. Aromatic heterocycles which have a factor Xa inhibitory activity are known, for example, from WO 96/10022. Substituted N- [(aminoimomethyl) phenylalkyl] -azaheterocyclylamides as inhibitors of factor Xa are described in WO 96/40679. The antithrombotic and anticoagulant effect of the compounds according to the invention is attributed to the inhibitory action against the activated coagulation protease, known as factor Xa, or to the inhibition of other activated serine proteases, such as the factor Vlla, factor IXa or thrombin. Factor Xa is one of the proteases that participates in the complex process of blood coagulation. Factor Xa catalyzes the conversion of proton bina to thrombin. Thrombin cleaves fibrinogen into fibrin monomers which, after crosslinking, contribute elementally to the formation of thrombi. An activation of thrombin can result in the presence of thromboembolic diseases. However, an inhibition of thrombin can inhibit the formation of fibrin that participates in the formation of thrombi. The inhibition of thrombin can be measured, for example, by the method of G. F. Cousins et al. in Circulation 1996, 94, 1705-1712. An inhibition of factor Xa can prevent, in this way, thrombin from forming. The compounds of the formula I according to the invention and their salts are involved in the blood coagulation process by inhibiting factor Xa, thereby inhibiting the formation of thrombi. The inhibition of factor Xa by the compounds according to the invention and the measurement of the anticoagulant and antithrombotic activity can be determined by conventional in vitro or in vivo methods. J. Haupt ann et al. describe an appropriate method, for example, in Thrombosis and Haemostasis 1990, 63, 220-223. The inhibition of factor Xa can be measured, for example, by the method of T. Hará et al. in Thromb. Haemostas. 1994, 71, 314-319. The coagulation factor Vlla initiates the extrinsic part of the coagulation cascade after binding with tissue factor and contributes to the activation of factor X in factor Xa. Inhibition of factor Vlla thus prevents the formation of factor Xa and thus a subsequent formation of thrombin. The inhibition of factor Vlla by the compounds according to the invention and the measurement of the anticoagulant and antithrombotic activity can be determined by means of conventional in vitro or in vivo methods. A conventional method for measuring the inhibition of factor Vlla is described, for example, by H. F. Ronning et al. in Thrombosis Research 1996, 84, 73-81. The coagulation factor IXa is generated in the intrinsic coagulation cascade and also participates in the activation of factor X in factor Xa. Consequently, an inhibition of factor IXa can prevent in a different way that factor Xa is formed. The inhibition of factor IXa by means of the compounds according to the invention and the measurement of the anticoagulant and antithrombotic activity can be determined by conventional in vi tro or in vivo methods. For example, J. Chang et al. describe an appropriate method in Journal of Biological Chemistry 1998, 273, 12089-12094.

The compounds according to the invention can also be used for the treatment of tumors, tumor diseases and / or tumor metastasis. T. Taniguchi and N. R. Lemoine indicated a correlation between tissue factor TF / factor Vlla and the development of several types of cancer in Biomed. Health Res. (2000), 41 (Molecular Pathogenesis of Pancreatic Cancer), 57-59. The publications listed below describe an anti-tumor action of TF-VII inhibitors and fac-tor Xa for various types of tumors: K. M. Donnelly et al. in Thromb. Haeost. 1998; 79: 1041-1047; E. G. Fischer et al. in J. Clin. Invest. 104: 1213-1221 (1999); B. M. Mueller et al. in J. Clin. Invest. 101: 1372-1378 (1998); M. E. Bromberg et al. in Thromb. Haemost. 1999; 82: 88-92. The compounds of the formula I can be used as medicated active ingredients in human and veterinary medicine, in particular, for the treatment and prevention of thromboembolic conditions such as thrombosis, myocardial infarction, arteriosclerosis, inflammations, stroke, angina pectoris, restenosis post-angioplasty, claudicatio intermittens, venous thrombosis, pulmonary embolism, arterial thrombosis, iocardial ischemia, unstable angina and apoplelic attack based on thrombosis. The compounds according to the invention are also used for the treatment or prophylaxis of atherosclerotic diseases such as coronary artery disease, cerebral arterial disease or peripheral arterial disease.

The compounds are also used in combination with other thrombolytic agents in myocardial infarction, in addition for prophylaxis for post-thrombolytic reocclusion, percutaneous transluminal angioplasty (PTCA) and coronary bypass operations. The compounds according to the invention are also used for the prevention of rethrombosis in microsurgery, also as anticoagulants in connection with artificial organs or in hemodialysis. The compounds are also used for the cleaning of catheters and medical aids in patients in vivo, or as anticoagulants to preserve blood, plasma and other blood products in vi tro. The compounds according to the invention are also used for those diseases in which the coagulation of the blood contributes crucially with the course of the disease or represents a source of secondary pathology as, for example, in cancer, including metastasis, inflammatory diseases, including arthritis, and diabetes. The compounds according to the invention are also used for the treatment of migraine (F. Morales-Asin et al., Headache, 40, 2000, 45-47). In the treatment of the diseases described, the compounds according to the invention are also used in combination with other thrombolytically active compounds as, for example, with the "tissue plasminogen activator" t-PA, modified t-PA, streptokinase or urokinase. The compounds according to the invention are administered with the other substances mentioned either at the same time or before or after. Particular preference is given to the simultaneous administration with aspirin, in order to avoid the recurrence of thrombus formation. The compounds according to the invention are also used in combination with the platelet glycoprotein receptor antagonists (Ilb / IIIa) which inhibit the aggregation of blood platelets. The subject of the invention are the compounds of the formula I and their salts, as well as a process for preparing the compounds of the formula I according to claim 1, as well as their salts, characterized in that a) for preparing compounds of the formula I wherein X is NH and Y is 0, a compound of the formula II is reacted wherein R1, R4, R4 ', E, Q, T, Z and Z' have the meanings indicated in claim 1, with a compound of formula III DN = C = 0 III where D has the meaning indicated in claim 1, or b) to prepare compounds of the formula I, wherein X and Y are 0, a compound of the formula IV is reacted wherein W, Y and T have the meaning indicated in claim 1, with a compound of formula V wherein X and Y are 0, L is Cl, Br, I or a free OH group or functionally reactive and R1 and D have the meanings indicated in claim 1, and / or a base or a base is converted acid of the formula I in one of its salts. Also object of the invention are the optically active forms (stereoisomers), the enantiomers, the racema-tss, the diastereomers, as well as the hydrates and solvates of these compounds. Solvates of the compounds are understood to be the adductions of inert solvent molecules to the compounds that are formed due to their attractive force mu-tua. Solvates are, for example, monohydrates or dihydrates or alcoholates. Derivatives of pharmaceutical use are, for example, the salts of the compounds according to the invention and also the so-called prodrug compounds. By prodrug derivatives are meant compounds of formula I which were modified, for example, with alkyl or acyl groups, sugars or oligopeptides, which are rapidly cloned in the organism to form the active compounds according to the invention. Also included herein are the biodegradable polymer derivatives of the compounds according to the invention, as described, e.g., in Int. J. Pharm. 115+ 61-67 (1995). The invention also relates to mixtures of the compounds of the formula I according to the invention, for example mixtures of two diastereoisomers, for example, in the ratio 1: 1, 1: 2, 1: 3, 1: 4. , 1: 5, 1:10, 1: 100 or 1: 1000. This involves, with particular preference, mixtures of stereoisomeric compounds. For all radicals that occur more than once, their meanings are independent of each other. Above and below, the radicals or parameters D, E, Q, T, X, Y, Z, Z ', R1, R4, R4' have the meanings indicated in formula I, unless otherwise expressly stated. . A is alkyl, is unbranched (linear) or branched, and has 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. A is preferably methyl, also ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or ter. -butyl, also pentyl, 1-, 2- or 3-methylbutyl, 1,1-, 1,2- or 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-, 2-, 3- or 4-methylpentyl , 1,1-, 1,2-, 1,3-, 2,2-, 2,3- or 3,3-dimethylbutyl, 1- or 2-ethylbutyl, 1-ethyl-1-methylpropyl, 1-ethyl -2-methylpropyl, 1,1,2- or 1,2,2-trimethylpropyl, for example, trifluoromethyl is also preferred. A is, with very special preference, alkyl having 1-6 grams of C, preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. -butyl, ter. -butyl, pentyl, hexyl or trifluoromethyl. The cycloalkyl has 3-7 C atoms and is preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.

Hal preferably means F, Cl or Br, but also I. Ar means, for example, phenyl, o-, m- or p-tolyl, o-, m- or p-ethylphenyl, o-, m- or p -propylphenyl, o-, m- or p-isopropylphenyl, or-, - or p-ter. -butylphenyl, o-, m- or p-hydroxyphenyl, o-, m- or p-nitrophenyl, o-, m- or p-aminophenyl, o-, m- or p- (N-methylamino) -phenyl, or -, m- or p- (N-methylaminocarbonyl) -phenyl, o-, m- or p-acetamidophenyl, o-, m- or p-methoxyphenyl, o-, m- or p-ethoxyphenyl, or-, m- or p-ethoxycarbonylphenyl, o-, - or p- (N, N-dimethylamino) -phenyl, o-, m- or p- (N, N-dimethylaminocarbonyl) -phenyl, o-, m- or p- (N -ethylamino) -phenyl, o-, m- or p- (N, N-diethylamino) -phenyl, o-, - or p-fluorophenyl, o-, m- or p-bromophenyl, o-, m- or p -chlorophenyl, o-, m- or p- (methylsulfonamido) -phenyl, o-, m- or p- (methylsulfonyl) -phenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-difluorophenyl, 2 are also preferred. , 3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dichlorophenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3, 5-dibromophenyl, 2,4- or 2,5-dinitrophenyl, 2,5- or 3,4-dimethoxyphenyl, 3-nitro-4-chlorophenyl, 3-amino-4-chloro-, 2-amino-3-chloro-, 2-amino-4-chloro-, 2-amino-5-chloro- or 2-amino-6-chlorophenyl, 2-nitro-4-N, N-dimethylamino- or 3- Nitro-4-N, N-dimethylaminophenyl, 2,3-diaminophenyl, 2,3,4-, 2,3,5-, 2,3,6-, 2,4,6- or 3,, 5-trichlorophenyl , 2,4,6-trimethoxyphenyl, 2-hydroxy-3,5-dichlorophenyl, p-iodophenyl, 3,6-dichloro-4-aminophenyl, 4-fluoro-3-chlorophenyl, 2-fluoro-4-bromophenyl, 2 , 5-difluoro-4-bromophenyl, 3-bromo-6-methoxyphenyl, 3-chloro-6-methoxyphenyl, 3-chloro-4-acetamidophenyl, 3-fluoro-4-methoxyphenyl, 3-amino-6-methylphenyl, 3 -chloro-4-aceta-idophenyl or 2,5-dimethyl-4-chlorophenyl. Ar preferably means, for example, unsubstituted or mono-, di- or trisubstituted phenyl with Hal, A, OR2, NR2COA, S02A, COOR2 or CN. Ar means, with special preference, for example phenyl unsubstituted or mono, di or trisubstituted with Hal, A, OR3 or NHCOA, such as, eg, phenyl, o-, - or p-methylphenyl, or-, m- or p-hydroxyphenyl, o-, m- or p-methoxyphenyl, 2-, 3- or 4-chlorophenyl, 4-bromophenyl, 3-fluoro-4-trifluoromethoxyphenyl, 4-ethoxyphenyl, 3-cyanophenyl, or -, m- or p-acetami-phenyl or 4-ethoxycarbonylphenyl. With very special preference, Ar is unsubstituted phenyl, 4-chlorophenyl, 4-fluorophenyl, 2,3-difluorophenyl, 2-chlorophenyl, 4-hydroxyphenyl, 2- or 4-methoxyphenyl or 4-acetamidophenyl. Ar 'preferably has the preferred meanings indicated in the case of Ar. Het means, for example, 2- or 3-furyl, 2- or 3-thienyl, 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or 5-imidazolyl, 1-, 3-, 4 - or 5-pyrazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 2-, 3 - or 4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl, 1, 2, 3-triazole-l-, -4- or -5-yl, 1,2,4-triazole- l-, -3- or -5-yl, 1- or 5-tetrazolyl, 1, 2, 3-oxadiazol-4- or -5-yl, 1, 2,4-oxadiazol-3 or 5-yl, 1, 3, 4-thiadiazol-2- or -5-yl, 1, 2,4-thiadiazol-3-y-5-yl, 1, 2, 3-thiadiazol-4- or -5-yl, 3- or 4-pyridazinyl, pyrazinyl, 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl, 4- or 5-isoindolyl, 1-, 2-, 4- or 5-benzimidazolyl, -, 3-, 4-, 5-, 6- or 7-benzopyrazolyl, 2-, 4-, 5-, 6- or 7-benzoxazolyl, 3-, 4-, 5-, 6- or 7-benzisoxazolyl, 2-, 4-, 5-, 6- or 7-benzothiazolyl, 2-, 4-, 5-, 6- or 7-benzisothiazolyl, 4-, 5-, 6- or 7-benz-2, 1, 3 -oxadiazolyl, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl, 3-, 4-, 5-, 6-, 7- or 8-cin olinyl, 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl, 5- or 6-quinoxalinyl, 2-, 3-, 5-, 6-, 7- or 8-2H-benzo [1 , 4] oxazinyl, 1,3-benzodioxol-5-yl, 1,4-benzodioxan-6-yl, 2,3-benzothiadiazol-4- or -5-yl or 2, 1, 3 are also preferred benzoxadiazol-5-yl. The heterocyclic radicals may also be partially or completely hydrogenated. Het can also mean, for example, 2,3-dihydro-2-, -3-, -4- or -5-furyl, 2,5-dihydro-2-, -3-, -4- or 5-furyl , tetrahydro-2- or -3-furyl, 1,3-dioxolan-4-yl, te-trahydro-2- or -3-thienyl, 2,3-dihydro-l-, -2-, -3-, -4- or -5-pyrrolyl, 2,5-dihydro-l-, -2-, -3-, -4- or -5-pyrrolyl, 1-, 2- or 3-pyrrolidinyl, tetrahydro-1-, -2- or -4-imidazolyl, 2,3-dihydro-l-, -2-, -3-, -4- or -5-pyrazolyl, tetrahydro-1-, -3- or -4-pyrazolyl, , 4-dihydro-l-, -2-, -3- or -4-pyridyl, 1, 2, 3, 4-tetrahydro-l-, -2-, -3-, -4-, -5- or -6-pyridyl, 1-, 2-, 3- or 4-piperidinyl, 2-, 3- or 4-morpholinyl, tetrahydro-2-, -3- or -4-pyranyl, 1,4-dioxanyl, 1, 3-dioxan-2-, -4- or -5-yl, hexahydro-1-, -3- or -4-pyridazinyl, hexahydro-1-, -2-, -4- or -5-pyrimidinyl, 1- , 2- or 3-piperazinyl, 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5-, -6-, -7- or -8-quinolyl, 1,2,3,4-tetrahydro-l-, -2-, -3-, -4-, -5-, -6-, -7- or -8-isoquinolyl, 2-, 3-, 5- , 6-, 7- or 8-3, 4-dihydro-2H-benzo [1,4] oxazinyl, is also pre fieren 2, 3-methylenedioxyphenyl, 3,4-methylenedioxyphenyl, 2,3-ethylenedioxyphenyl, 3,4-ethylenedioxyphenyl, 3,4- (difluo-romethylenedioxy) phenyl, 2,3-dihydrobenzofuran-5- or 6-yl, 2,3 - (2-oxo-methylenedioxy) -phenyl or also 3,4-dihydro-2H-1, 5-benzodioxepin-6- or -7-yl, 2,3-dihydro-benzofuranyl or 2,3-dihydro are also preferred -2-oxo-furanyl. Het preferably means a saturated, unsaturated or aromatic mono or bicyclic heterocycle with 1 to 2 N, O and / or S atoms, which may be unsubstituted or mono- or disubstituted with the oxygen of the carbonyl, OH or OA. Het is preferably, for example, furyl, thienyl, thiazolyl, imidazolyl, [2, 1, 3] -benzothiadiazolyl, oxazolyl, pyridyl, indolyl, piperidinyl, morpholinyl, tetrahydropyranyl, piperazinyl, pyrazinyl, piperidinyl or pyrrolidinyl, optionally substituted with carbonyl oxygen, such as, for example, 3-oxo-morpholin-4-yl, 2-oxo-piperidin-1-yl or 2-oxo-pyrrolidin-1-yl. Het means, with very special preference, thienyl, imidazolyl, pyridyl, indolyl, piperidinyl, piperazinyl, 2-oxo-piperazinyl, morpholinyl, tetrahydropyran-4-yl, 3-oxo-morpholin-4-yl, 2-oxo-2H- pyrazin-1-yl, 2-oxo-pyrrolidin-1-yl or 2-oxo-piperidin-1-yl. Het 'preferably has the preferred meanings indicated in the case of Ar. D denotes, in particular, for example phenyl unsubstituted or mono- or di-substituted with Hal, A, hydroxy, methoxy, ethoxy, hydroxycarbonyl, methoxycarbonyl or ethoxycarbonyl, or pyridyl or thienyl unsubstituted or monosubstituted with Hal. D means, with very special preference, 4-chlorophenyl. R1 preferably means Ar, such as, for example, phenyl, o-, m- or p-fluorophenyl, o-, m- or p-chlorophenyl, o-, m- or p-hydroxyphenyl, or-, m- or p-methoxyphenyl or difluoro-phenyl; Het, such as, for example, thienyl or furyl; cycloalkyl such as, for example, cyclohexyl; or A, which may be monosubstituted with OR2, such as, for example, methyl, ethyl, propyl, butyl, -CH (CH3) 0H or -CH (CH3) 0CH3. R1 signifies, with special preference, phenyl unsubstituted or mono, di or trisubstituted with Hal, OH or OA, such as, for example, phenyl, o-, m- or p-fluorophenyl, o-, - or p-chlorophenyl , o-, m- or p-hydroxyphenyl, o-, m- or p-ethoxyphenyl, difluorophenyl or trifluorophenyl; a monocyclic aromatic heterocycle with 1 to 2 N, 0 and / or S atoms, such as, for example, thienyl or furyl; or A, which may be monosubstituted with OR3, such as, for example, methyl, ethyl, propyl, butyl, -CH (CH3) OH or -CH (CH3) OCH3. R 2 preferably means, for example, H or alkyl with 1, 2, 3, 4, 5 or 6 C atoms, with very special preference H. R 3 is preferably, for example, H or alkyl with 1, 2, 3 , 4, 5 or 6 C atoms, with very special preference, H. R 4, R 4 'are preferably A, OH, OA or absent; methylene or ethylene are also together. R4, R4 'signify, with special preference, "is absent". T preferably means a saturated, unsaturated or aromatic mono or bicyclic heterocycle with 1 to 2 N, O and / or S atoms, which may be unsubstituted or mono- or di-substituted with A or carbonyl oxygen (= 0), phenyl unsubstituted or mono, di or trisubstituted with Hal, OR2 or NR2C0A, or a saturated unsubstituted monocyclic carbocycle. The saturated unsubstituted carbocycle preferably means cyclopentyl or cyclohexyl. T denotes, with particular preference, a saturated or aromatic monocyclic heterocycle with 1 to 2 N and / or O atoms, which may be unsubstituted or mono- or di-substituted with A or carbonyl oxygen (= 0), unsubstituted phenyl or mono, di or trisubstituted with Hal, OH, OA or NHCOA, or an unsubstituted, saturated monocyclic carbocycle. > T denotes in particular piperidin-yl, piperazinyl, pyridinyl, 2-oxopiperidin-1-yl, 2-oxo-piperidin-4-yl, 2-oxo-pyrrolidin-1-yl, pyrrolidin-1-yl, 2-oxo- lH-pyridin-1-yl, 3-oxo-morpholin-4-yl, morpholin-4-yl, 4-oxo-lH-pyridin-1-yl, 2,6-dioxo-piperidin-1-yl, 2- oxo-piperazin-1-yl, 2,6-dioxo-piperazin-1-yl, 2,5-dioxo-pyrrolidin-1-yl, 2-oxo-l, 3-oxazolidin-3-yl, pyridazinyl, 3- oxo-2H-pyridazin-2-yl, 2-caprolactam-1-yl (= 2-oxo-azepan-1-yl), 6-oxo-piperazin-1-yl, 2-aza-bicyclo [2.2.2] -octan-3-on-2-yl, 5,6-dihydro-lH-pyrimidin-2-oxo-l-yl, 2-oxo- [1, 3] oxazinan-3-yl or 4H- [1, 4 ] oxazin-4-yl, wherein the radicals may additionally be monosubstituted with A, are unsubstituted phenyl or mono, di or trisubstituted with Hal, OH, OA or NHCOA, or an unsubstituted, saturated monocyclic carbocycle. T is unsubstituted piperidin-1 or 4-yl or monosubstituted with A and / or carbonyl oxygen (= 0), piperazinyl, morpholin-4-yl or unsubstituted cyclohexyl. In a particularly preferred embodiment, R4, R4 'are absent, Z, Z' are in each case ethylene, E is CH or N, T is unsubstituted piperidin-1 or -4-yl or monosubstituted with A, 2- oxo-piperazin-1-yl, morpholin-4-yl or unsubstituted cyclohexyl. The compounds of the formula I can have one or several chiral centers and, consequently, can be present in various stereoisomeric forms. Formula I comprises all these forms. Accordingly, the invention relates in particular to those compounds of the formula I, wherein at least one of the radicals mentioned has one of the preferred meanings indicated above. Some preferred groups of compounds can be expressed through the following subformulas the a Is, which correspond to formula I and wherein the radicals not designated in greater detail have the meaning indicated in formula I, but where in D is phenyl unsubstituted or mono or disubstituted with Hal, A, OR2 or COOR2, or unsubstituted or monosubstituted pyridyl with Hal; in Ib D is monosubstituted phenyl with Hal; in R2 it is H or A; in Id T is a saturated, unsaturated or aromatic mono or bicyclic heterocycle with 1 to 2 N, O and / or S atoms, which may be unsubstituted or mono or disubstituted with A or carbonyl oxygen (= 0), phenyl unsubstituted or mono, di or trisubstituted with Hal, OR2 or NR2C0A, or an unsubstituted, saturated monocyclic carbocycle; where Q is absent, it is 0 or CH2; in If Ar is unsubstituted phenyl or mono, di or trisubstituted with Hal, A, OR2, NR2C0A, S02A, S02NH2, COOR2 or CN; in Ig Ar is phenyl unsubstituted or mono, di or trisubstituted with Hal, A, OR3 or NR3C0A; in Ih R1 is Ar, Het, cycloalkyl or A, which may be monosubstituted with OR2; in Ii R1 is phenyl unsubstituted or mono, di or trisubstituted with Hal, OH or OA, an aromatic monocyclic heterocycle with 1 to 2 N, 0 and / or S, or A atoms, which may be monosubstituted with OR3; in Ij Het is a saturated, unsaturated or aromatic mono or bicyclic heterocycle with 1 to 2 N, 0 and / or S atoms, which may be unsubstituted or mono- or di-substituted with A or carbonyl oxygen (= 0); in Ik Y is O; in II X is NR3 'or O, R3' is H; in Im Z, Z 'are ethylene; in In T is a saturated or aromatic monocyclic heterocycle with 1 to 2 N and / or 0 atoms, which may be unsubstituted or mono or disubstituted with A or carbonyl oxygen (= 0), unsubstituted or mono, di or trisubstituted phenyl with Hal, OH, OA or NHCOA, or an unsubstituted, saturated monocyclic carbocycle; where A is unbranched or branched alkyl with 1-10 C atoms, wherein 1-7 H atoms may be replaced by F; in Ip D is unsubstituted or mono- or disubstituted phenyl with Hal, A, OR2 or COOR2, or unsubstituted or monosubstituted pyridyl with Hal, X is NR3 or 0, • Y is 0, R1 is Ar, Het, cycloalkyl or A, which may be be monosubstituted with OR2, E is CH or N, Z, Z 'are ethylene, Q is absent, is O or CH2, R2 is H or A, R3 is H or A, R4, R4' each, independently between yes, it is absent, they are A, OH or OA, R4 and R4 'are also together methylene or ethylene, T is a saturated or aromatic monocyclic heterocycle with 1 to 2 N and / or 0 atoms, which may be unsubstituted or mono or disubstituted with A or carbonyl oxygen (= 0), unsubstituted or mono phenyl, di or trisubstituted with Hal, OH, OA or NHCOA, or an unsubstituted, saturated monocyclic carbocycle, A is unbranched alkyl, or branched with 1-10 C atoms, where 1-7 H atoms can be replaced by F, Ar is unsubstituted phenyl or mono, di or trisubstituted with Hal, A, OR2, NR2C0A, S02A, S02NH2, C0-OR2 or CN, Het is a saturated, unsaturated or aromatic mono or bicyclic heterocycle with 1 to 2 N, 0 and / or S atoms, which may be unsubstituted or mono- or di-substituted with A or carbonyl oxygen (= 0), Hal is F, Cl, Br or I, p is 1, 2, 3, 4 or 5; D is phenyl monosubstituted with Hal, X is NR3 'or 0, Y is 0, R1 is phenyl unsubstituted or mono, di or trisubstituted with Hal, OH or OA, an aromatic monocyclic heterocycle with 1 to 2 N, 0 and / or N atoms. or S, A, which may be monosubstituted with OR, R3 'is H, E is CH or N, Z, Z' are ethylene, Q is absent, is 0 or CH2, R2 is H or A, R3 is H or A, R4, R4 'each, independently of one another, is absent, are A, OH or OA, R4 and R4' are also together methylene or ethylene, T is a saturated or aromatic monocyclic heterocycle with 1 to 2 N atoms and / or 0, which may be unsubstituted or mono or disubstituted with A or carbonyl oxygen (= 0), unsubstituted or mono, di or trisubstituted phenyl with Hal, OH, OA or NHCOA, or an unsubstituted, saturated monocyclic carbocycle, A is alkyl unbranched or branched with 1-10 C atoms, wherein 1-7 H atoms may be replaced by F, Hal is F, Cl, Br or I; D is phenyl monosubstituted with Hal, X NR3 'or O, Y is O, R1 is thienyl, furyl, phenyl unsubstituted or mono, di or trisubstituted with Hal, OH or OA or A, which may be monosubstituted with OR3, R3 is H or A, RJ is H, E is CH or N, Z, Z 'is ethylene, Q is absent, is O or CH2, R ^ is H or A, R3 is H or A, R4, R4' each, of independently of one another, absent, are A, OH or OA, R4 and R4 'are also together methylene or ethylene, T is piperidinyl, piperazinyl, pyridinyl, 2-oxo-piperidin-1-yl, 2-oxo-piperidin-4 -yl, 2-oxo-pyrrolidin-1-yl, pyrrolidin-1-yl, 2-oxo-lH-pyridin-1-yl, 3-oxo-morpholin-4-yl, morpholin-4-yl, 4 -oxo-lH-pyridin-1-yl, 2,6-dioxo-piperidin-1-yl, 2-oxo-piperazin-1-yl, 2,6-dioxo-piperazin-1-yl, 2,5-dioxo - pyrrolidin-1-yl, 2-oxo-l, 3-oxazolidin-3-yl, pyridazinyl, 3-oxo-2H-pyridazin-2-yl, 2-caprolactam-l-yl (= 2-oxo-azepam l-yl), 6-oxo-piperazin-1-yl, 2-aza-bicyclo [2.2.2] -octan-3-on-2-yl, 5,6-dihydro-lH-pyrimidin-2-yl oxo-l-yl, 2-oxo- [1, 3] oxazinan-3-yl or 4H- [1,4] oxazin-4-yl, wherein the radicals may additionally be monosubstituted with A, unsubstituted phenyl or mono, di or trisubstituted with Hal, OH, OA or NHCOA, or an unsubstituted, saturated monocyclic carbocycle, A is unbranched or branched alkyl with 1-10 C atoms, wherein 1-7 H atoms may be replaced by F, Hal is F, Cl, Br or I; D is phenyl monosubstituted with Hal, X is NR3 or 0, Y is O, R1 is thienyl, furyl, phenyl unsubstituted or mono, di or trisubstituted with Hal, OH or OA, A, which may be monosubstituted with OR 'R3 is H or A, RJ is H, E is CH or N, Z is ethylene, Z 'is ethylene, Q is absent, is 0 or CH2, R2 is H or A, RJ is H or A, R4, R4' is absent, R4 and R4 'are also together methylene or ethylene, T is unsubstituted piperidin-1- or 4-yl or monosubstituted with A and / or carbonyl oxygen (= 0), piperazinyl or morpholin-4-yl or unsubstituted cyclohexyl, A is unbranched or branched alkyl with 1-10 C atoms, wherein 1-7 H atoms may be replaced by F, Hal is F, Cl, Br or I; as well as its derivatives, solvates and stereoisomers of pharmaceutical utility, including their mixtures in all proportions. The compounds of the formula I and also the starting substances for their preparation are additionally obtained by methods known per se, such as are described in the literature (for example, in standard works such as Hou-ben-Weyl, Methoden der organischen Chemie [Methods of organic chemistry], Georg-Thieme-Verlag, Stuttgart), to be accurate, under reaction conditions that are known and appropriate for the reactions mentioned. The variants known per se can also be used here, but are not mentioned here in greater detail. If desired, the starting substances can also be formed on their own so that they are not isolated from the reaction mixture, but are instead immediately converted to the compounds of the formula I. Compounds can preferably be obtained of the formula I, wherein X is NH and Y is O, by reacting compounds of the formula II with compounds of the formula III. The reaction is carried out, generally, in an inert solvent, optionally in the presence of an organic base such as triethylamine, dimethylaniline, pyridine or quinoline. Depending on the conditions used, the reaction time ranges from a few minutes to 14 days, preferably between one and ten hours, the reaction temperature ranges between about 0 ° and 150 °, normally between 10 ° and 130 °, preferentially between 10? and 902, with very special preference between 202 and 80a. Suitable inert solvents are, for example, water; hydrocarbons, such as hexane, petroleum ether, benzene, toluene or xylene; chlorinated hydrocarbons, such as tri-chloroethylene, 1,2-dichloroethane, carbon tetrachloride, chloroform or dichloromethane; alcohols, such as methanol, ethanol, isopropanol, n-propanol, n-butanol or tert-butanol; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran (THF) or dioxane; glycol ethers such as ethylene glycol monomethyl or mono-ethyl ether (methyl glycol or ethyl glycol), ethylene glycol dimethyl ether (diglyme); ketones such as acetone or butanone; amides such as acetamide, dimethylacetamide or dimethylformamide (DMF); nitriles such as acetonitrile; sulphoxides such as dimethylsulfoxide (DMSO); carbon disulfide; carboxylic acids such as formic acid or acetic acid; nitroderivatives such as nitromethane or nitrobenzene; esters such as ethyl acetate, or mixtures of the mentioned solvents. The starting substances of formulas II and III are generally known. If they are new, they can then be prepared in accordance with methods known per se. The compounds of the formula I, wherein X and Y are O, can also be obtained by reacting compounds of the formula IV with compounds of the formula V.

In the compounds of the formula V, L is preferably Cl, Br, I or a reactive modified OH group, such as, for example, an activated ester, an imidazolide or alkylsulfonyloxy having 1-6 carbon atoms (preferably methyl) -sulfonyloxy or trifluoromethylsulfonyloxy) or arylsulfonyloxy with 6-10 C atoms (preferably phenyl- or p-tolylsulfonyloxy). Radicals of this type to activate the carboxyl group in typical acylation reactions are described in the literature (for example, in standard works such as Hou-ben-Weyl, Methoden der organischen Chemie [Methods of organic chemistry], Georg-Thie e Verlag, Stuttgart). Activated esters are advantageously formed in situ, for example by adding HOBt or N-hydroxysuccinimide. The reaction is carried out, in general, in an inert solvent, in the presence of an acid-binding agent, preferably a hydroxide, a carbonate or a bicarbonate of alkali or alkaline-earth metals, or another salt of a weak acid of metals alkaline or alkaline earth, preferably potassium, sodium, calcium or cesium. It is also favorable to add an organic base such as triethylamine, dimethylaniline, pyridine or quinoline, or an excess of the amino component of formula IV. Depending on the conditions used, the reaction time ranges from a few minutes to 14 days, and the reaction temperature ranges from about 0 ° to 150 °, usually between 20 ° and 130 °. Suitable inert solvents are those mentioned above. Pharmaceutical salts and other forms The compounds according to the invention mentioned can be used in their non-saline final form. On the other hand, the present invention also comprises the use of these compounds in the form of their pharmaceutically innocuous salts which can be derived from various organic and inorganic acids and bases according to procedures known to those skilled in the art. The pharmaceutically innocuous salt forms of the compounds of the formula I are prepared in a large majority in a conventional manner. Provided that the compound of formula I contains a carboxylic acid group, one of its appropriate salts can be formed by reacting the compound with a suitable base in the salt by the addition of corresponding bases. Bases of this type are, for example, alkali metal hydroxides, among them potassium hydroxide, sodium hydroxide and lithium hydroxide; alkaline earth metal hydroxides such as barium hydroxide and calcium hydroxide; alkali metal alcoholates, for example potassium ethanolate and sodium propanolate; as well as different organic bases such as piperidine, diethanolamine and N-methylglutamine. The aluminum salts of the compounds of the formula I are also counted here. In certain compounds of the formula I acid addition salts are formed by treating these compounds with pharmaceutically innocuous organic and inorganic acids, for example hydrohalic acids such as hydrochloric acid, hydrobromic acid or hydroiodic acid, other mineral acids and their corresponding salts such as sulphate , nitrate or phosphate and the like, as well as alkyl- and onoarylsulfonates such as ethanesulfonate, toluenesulfonate and benzenesulfonate, as well as other organic acids and their corresponding salts such as acetate, trifluoroacetate, tartrate, maleate, succinate, citrate, benzoate, salicylate, ascorbate and Similar. Accordingly, among the pharmaceutically acceptable acid addition salts of the compounds of the formula I are the following: acetate, adipate, alginate, arginate, aspartate, benzoate, benzenesulfonate (besylate), bisulfate, bisulfite, bromide, butyrate, canferate, canfersulfonate, caprilate, chloride, chlorobenzoate, citrate, cyclopentanpropionate, digluconate, dihydrogen phosphate, dinitrobenzoate, do-decyl sulfate, ethanesulfonate, fumarate, galacraterate (from mucic acid), galacturonate, glucoheptanoate, gluconate, glutamate , glycerophosphate, hemisuccinate, hemisulfate, hepta-noate, hexanoate, hippurate, hydrochloride, hydrobromide, iodide, 2-hydroxyethanesulfonate, iodide, isethionate, isobutyrate, lactate, lactobionate, malate, maleate, malonate, raan-delato, metaphosphate, methanesulfonate, methylbenzoate, monohydrate -diene-phosphate, 2-naphthalenesulfonate, nicotinate, nitrate, oxalate, oleate, patoate, pectinate, persulfate, phenylacetate, 3-phenylpropionate, phosphate, phosphonate, phthalate, which do not represent any limitations. Furthermore, salts of aluminum, ammonium, calcium, copper, iron (III), iron (II), lithium, magnesium and manganese (among others) are among the basic salts of the corallings according to the invention. III), manganese (II), potassium, sodium and zinc, which should not represent any limitation. Among the abovementioned salts, ammonium is preferred; the alkali metal salts sodium and potassium, as well as the alkaline earth metal salts calcium and magnesium. Among the salts of the compounds of formula I which are derived from non-toxic, pharmaceally acceptable organic bases, are primary, secondary and tertiary amine salts, substituted amines, including also natural substituted amines, cyclic amines as well as basic ion exchange resins. , eg arginine, betaine, caffeine, chloroprocaine, choline, N, N'-dibenzylethylenediamine (benzathine), dicyclohexylamine, diethanolamine, diethylamine, 2-diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, ethylene diamine, N-ethylmorpholine , N-ethylpiperidine, glucamine, gluco-sa, histidine, hydrabamine, isopropylamine, lidocaine, lysine, meglumine, N-methyl-D-glucamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purine, teo-bromine, triethanolamine, triethylamine, trimethylamine, tripro-phenylamine, as well as tris- (hydroxymethyl) -methylamine (tromethamine), which should not represent any limitation. Compounds of the present invention containing basic groups can be quaternized with nitrogen, with agents such as alkyl halides (C __-C), for example methyl, ethyl, isopropyl and tert-butyl chloride, bromide and iodide; dialkyl (C_-C) -sulfates, for example dimethyl-, diethyl- and dia ilsulfate; alkyl halides (C___-C__8), for example decyl, dodecyl, lauryl, myristyl and stearyl chloride, bromide and iodide; as well as aryl-alkyl halides (C_-C), for example benzyl chloride and phenethyl bromide. With salts of this type, compounds according to the invention soluble in both water and oil can be prepared. Among the above-mentioned preferred pharmaceal salts are acetate, trifluoroacetate, besylate, citrate, fumarate, gluconate, hemisuccinate, hipurate, hydrochloride, hydrobromide, isethionate, mandelate, meglumine, nitrate, oleate, phosphonate, pivalate, phosphate, sodium, stearate, sulfate, sulfosalicylate, tartrate, thiolate, tosylate and tromethamine, which should not represent any limitations. The acid addition salts of basic compounds of the formula I are prepared by contacting the free basic form with a sufficient amount of the desired acid, the salt being obtained in the usual manner. The free base can be regenerated by contacting the salt form with a base and isolating the free base in the usual manner. The basic free forms are distinguished in a sense from their corresponding salt forms in terms of certain physical properties, such as solubility in polar solvents; however, within the scope of the invention, the salts correspond, moreover, to their corresponding free basic forms. As mentioned, the pharmaceally innocuous base addition salts of the compounds of the formula I are formed with metals or amines such as alkaline or alkaline earth metals or organic amines. Preferred metals are sodium, potassium, magnesium and calcium. Preferred organic amines are NjN'-o .benzylethylenediamine, chloroprocaine, choline, diethanolane, ethylendiapdane, N-methyl-D-glucamine and procaine. The base addition salts of the acidic compounds according to the invention are prepared by contacting the free acid form with a sufficient amount of the desired base, the salt being obtained in the usual manner. The free acid can be regenerated by contacting the salt form with an acid and isolating the free acid in the usual manner. The free acid forms are distinguished in a sense from their corresponding salt forms with respect to certain physical properties such as solubility in polar solvents; however, within the scope of the invention, the salts correspond, moreover, to their relevant free acid forms. If a compound according to the invention contains more than one group that can form pharmaceally innocuous salts of this type, the invention also comprises multiple salts. Among typical multiple salt forms are counted, for example, bitartrate, diacetate, difumarate, dimeglumine, diphosphate, disodium and trichlorhydrate, which should not represent any limitation. As regards the above, it can be seen that, by "pharmaceutically safe salt" in the present context, an active principle is understood to contain a compound of the formula I in the form of one of its salts, especially when this salt form confers it at the beginning active improved pharmacokinetic properties, in comparison with the free form of the active principle or another saline form of the active principle that was previously used. The pharmaceutically safe salt form of the active ingredient can also give this active principle only a desired pharmacokinetic property that it did not previously have, and can even positively affect the pharmacodynamics of this active principle with respect to its therapeutic efficacy in the body. The compounds of the formula I can be chiral due to their molecular structure and, therefore, can be present in several enantiomeric forms. Therefore, they can also exist in racemic or optically active form. As the pharmaceutical activity of the racemates or stereoisomers of the compounds according to the invention may differ, the use of the enanti-mers may be desired. In these cases, the final product or even the intermediates can be separated into enantiomeric compounds by chemical or physical actions known to those skilled in the art or even used as such in the synthesis. In the case of racemic amines, the diastereomers are formed from the mixture by reaction with an optically active resolving agent. Suitable resolving agents are, for example, optically active acids, such as the R and S forms of tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid, appropriately N-protected amino acids (e.g. N-benzoylproline or N-benzenesulfonylproline) or the different optically active camphorsulfonic acids. The chromatographic resolution of the enantiomers by means of an optically active resolving agent (eg, dinitrophenolylphenylglycine, cellulose triacetate or other derivatives of carbohydrates or chirally derived methacrylate polymers immobilized on silica gel) is also advantageous. Suitable eluents for this purpose are mixtures of aqueous or alcoholic solvents, such as, for example, hexa-no / isopropanol / acetonitrile, for example in the volume ratio of 82: 15: 3. The invention also relates to the use of the compounds of the formula I and / or their physiologically acceptable salts to obtain pharmaceutical preparations, in particular by non-chemical methods. In this case, they can be converted into an appropriate dosage form together with at least one solid, liquid and / or semi-liquid excipient or adjuvant and, if desired, in combination with one or more active ingredients. Also the subject of the invention are medicaments comprising at least one compound of the formula I and / or its derivatives, solvates and stereoisomers of pharmaceutical utility, including their mixtures in all proportions, as well as optionally excipients and / or adjuvants. The pharmaceutical formulations can be administered in the form of dosage units containing per unit dose a predetermined quantity of active ingredient. A unit of this type can contain, for example, 0.5 mg to 1 g, preferably 1 mg to 700 mg, with special preference, 5 mg to 100 mg of a compound according to the invention, in accordance with the pathological condition treated, the route of administration and the age, weight and condition of the patient, or pharmaceutical formulations can be administered in the form of dosage units containing a predetermined amount of active ingredient per unit dose. Preferred unit dosage formulations are those that contain a daily dose or a partial dose, as indicated above, or a corresponding fraction thereof of an active ingredient. On the other hand, pharmaceutical formulations of this type can be prepared with a general knowledge process in the specialized pharmaceutical field. The pharmaceutical formulations can be adapted to be administered by any appropriate route, for example, oral (including buccal or sublingual), rectal, nasal, topical (including buccal, sublingual or transdermal), vaginal or parenteral (including the subcutaneous, intramuscular, intravenous or intradermal route). Formulations of this type can be prepared with all known processes in the specialized pharmaceutical field, for example by combining the active principle with the excipient (s) or adjuvants. Pharmaceutical formulations adapted for oral administration can be administered as separate units such as, for example, capsules or tablets.; powders or granulates; solution or suspensions in aqueous or non-aqueous liquids; edible foams or mousses; or liquid emulsions of oil in water or liquid emulsions of water in oil. Thus, for example, in the oral administration in the form of a tablet or capsule, the active component can be combined with an oral, non-toxic and pharmaceutically innocuous inert excipient, such as, for example, ethanol, glycerin, water, etc. Powders are prepared by grinding the compound to an appropriate fine size and mixing it with a crushed pharmaceutical excipient in the same manner as, for example, an edible carbohydrate such as, for example, starch or mannitol. There may also be a flavoring, a preservative, a dispersant and a colorant. The capsules are obtained by preparing a powder mixture as described above and filling molded gelatin shells with it. Lubricants such as, p. ex. , high dispersion silicic acid, talc, magnesium stearate, calcium stearate or polyethylene glycol in solid form can be added to the powder mixture before the filling process. Also, a disintegrant or a solubilizer, such as, for example, can be added. , agar-agar, calcium carbonate or sodium carbonate, in order to improve the availability of the medication after the capsule is ingested. In addition, if desired or necessary, suitable binders, lubricants and disintegrants, as well as colorants, can be incorporated into the mixture. Suitable binders are starch, gelatin, natural sugars such as, for example, glucose or beta-lactose, corn sweeteners, natural and synthetic gum such as, for example, acacia, tragacanth or sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes, etc. The lubricants used in these dosage forms include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, etc. Disintegrants include, but are not limited to, starch, methylcellulose, agar, bentonite, xanthan gum, etc. The tablets are formulated by preparing, for example, a powder mixture, granulating or compressing it dry, adding a lubricant and a disintegrant and compressing everything into tablets. A pulverulent mixture is prepared by mixing a comminuted compound in a suitable manner with a diluent or a base, as described above, and optionally with a binder such as, for example, carboxymethylcellulose, an alginate, gelatin or polyvinylpyrrolidone, a reagent the solution as, for example, paraffin, a resorption accelerator such as, for example, a quaternary salt and / or an absorption agent such as, for example, bentonite, kaolin or dicalcium phosphate. The powder mixture can be granulated by wetting it with a binder such as, for example, syrup, starch, paste, acadia or solutions of cellulosic or polymeric materials, and pressing it through a screen. As an alternative to the granulation, it is allowed to pass. the powder mixture by a tabletting machine, where inhomogeneous molded lumps are formed which are split into granules. The granulates can be lubricated by the addition of stearic acid, a stearate salt, talc or mineral oil, in order to prevent them from sticking to the molten molds for tablets. The lubricated mixture is then compressed to form tablets. The compounds according to the invention can also be combined with a fluid inert excipient and then compressed directly into tablets without performing granulation or dry compression steps. There may also be a transparent or non-transparent protective layer composed of a shellac coating, a layer of sugar or polymeric material and a shiny layer of wax. To these coatings dyes can be added to differentiate the different dose units. Oral liquids, such as solutions, syrups and elixirs, they can be prepared in the form of dosage units, so that a given amount contains a predetermined amount of compound. The syrups can be prepared by dissolving the compound in an aqueous solution with appropriate flavor, while the elixirs are prepared using a non-toxic alcoholic vehicle. The suspensions can be formulated by dispersing the compound in a non-toxic vehicle. In addition, solubilizers and emulsifiers may be added, such as, for example, ethoxylated isostearic alcohols and polyoxyethylene sorbitol ethers, preservatives, flavoring additives such as, for example, peppermint oil or natural sweeteners or saccharin or other artificial sweeteners, etc. Formulations of dosage units for oral administration may optionally be included in microcapsules. The formulation can thus be prepared so that the release is prolonged or delayed as, e.g. ex. , by coating or inclusion of particulate material in polymers, waxes, etc. The compounds of the formula I as well as their salts, solvates and physiologically functional derivatives can be administered in the form of liposome delivery systems as, for example, small unilamellar vesicles, large unilamellar vesicles and multilamellar vesicles. Liposomes can be formed from various phospholipids such as, for example, cholesterol, stearylamine or osphidylcholine The compounds of the formula I, as well as their salts, solvates and physiologically functional derivatives can be supplied using monoclonal antibodies as carriers The polymers can also be coupled with soluble polymers as targeted medicament carriers Polymers of this type can comprise polyvinylpyrrolidone, pyran copolymer, polyhydroxypropylmethacrylamide phenol, polyhydroxyethylaspartamide phenol or polylysine In addition, the compounds may be coupled to a class of biodegradable polymers which are suitable for achieving a controlled release of a medicament, for example, polylactic acid, polyepsilon-caprolactone, polyhydroxybutyric acid, polyorthode, polyethylene oxide, substituted with palmitoyl radicals. s teres, polyacetals, polydihydroxypyrans, polycyanoacrylates and cross-linked or unfriendly block copolymers of hydrogels. Pharmaceutical formulations adapted for transdermal administration can be administered as separate patches for prolonged close contact with the epidermis of the recipient. In this way, for example, the active principle of the patch can be administered by means of iontophoresis, as is generally described in Pharmaceutical Research, 3 (6), 318 (1986).

The pharmaceutical compositions adapted for topical administration can be formulated in the form of ointments, creams, suspensions, lotions, powders, solutions, pastes, gels, sprays, aerosols or oils. For eye treatments or other external tissues, for example, the mouth and the skin, the formulations are preferably applied as ointment or topical cream. In case of formulating an ointment, the active principle can be applied with either a paraffinic cream base or a water miscible one. Alternatively, the active ingredient can be formulated in a cream with a creamy base of oil in water or a base of water in oil. Pharmaceutical formulations adapted to topical application in the eyes include ophthalmic drops, wherein the active principle is dissolved or suspended in an appropriate support, especially an aqueous solvent. Pharmaceutical formulations adapted to topical application in the mouth comprise oral dissolution tablets, lozenges and mouth rinses. Pharmaceutical formulations adapted to rectal application can be administered in the form of ovules or enemas. Pharmaceutical formulations adapted for nasal administration, in which the support substance is a solid substance, contain a coarse powder with a granulometry within the range, for example, of 20-500 micrometers, which is administered in the manner in which it is administered. Snuff was inhaled, that is, inhaled quickly through the nasal passages from a container with the powder held close to the nose. Suitable formulations for administration as a nasal spray or nasal drops with a liquid as a support substance comprise active substance solutions in water or oil. Pharmaceutical formulations adapted for administration by inhalation comprise powders of fine particles or mists that can be generated by means of different types of pressurized dispensers with aerosols, nebulizers or insufflators. Pharmaceutical formulations adapted for vaginal administration can be administered as pessaries, tampons, creams, gels, pastes, foams or spray formulations. Pharmaceutical formulations adapted for parenteral administration include sterile aqueous and non-aqueous injectable solutions, containing antioxidants, buffers, bacteriostats and solutes, through which the formulation becomes isotonic with the patient's blood in treatment; as well as sterile aqueous and non-aqueous suspensions which may contain suspending agents and thickeners. The formulations can be administered in single or multiple dose containers, for example, sealed ampoules and vials and stored in the lyophilized state, so that only the addition of the sterile carrier liquid, eg, water for the patient, is required. injectables, immediately before use. Injectable solutions and solutions prepared according to the recipe can be prepared from powders, granules and tablets. It is understood that the formulations, in addition to the components mentioned above in particular, may contain other agents customary in the specialized field with respect to the corresponding type of formulation; in this way, the appropriate formulations for oral administration may contain flavors. An amount of therapeutic efficacy of a compound of the formula I depends on a number of factors, including for example the age and weight of the animal, the exact health status that requires treatment, as well as its severity, the nature of the formulation as well as the route of administration, and ultimately is determined by the attending physician or veterinarian. However, an effective amount of a compound according to the invention generally varies in the range of 0.1 to 100 mg / kg of body weight of the receptor (mammal) per day and especially, typically, in the range of 1 to 10. mg / kg of body weight per day. In this way, for a 70 kg adult mammal the effective amount per day would usually be from 70 to 700 mg, where this amount may be administered as a single dose per day or usually in a series of partial doses (as, for example, two, three, four, five or six) per day, so that the total daily dose is the same. An effective amount of a salt or solvate or one of its physiologically functional derivatives can be determined per se as part of the effective amount of the compound according to the invention. It can be assumed that similar do-sis are appropriate for the treatment of the other pathological conditions mentioned above. The compounds of formula I and their physiologically acceptable salts can be used in the combat and prevention of thromboembolic conditions such as thrombosis, myocardial infarction, arteriosclerosis, inflammation, stroke, angina pectoris, post-angioplasty restenosis, claudicatio intermittens , migraine, tumors, tumor diseases and / or tumor metastasis. Furthermore, the subject of the invention are medicaments which contain at least one compound of formula I and / or its derivatives, solvates and stereoisomers of pharmaceutical use, including their mixtures in all proportions, and at least one other active drug ingredient. Also a subject of the invention is a kit consisting of separate packages of (a) an effective amount of a compound of formula I and / or its derivatives, solvates and stereoisomers of pharmaceutical utility, including their mixtures in all proportions, and ( b) an effective amount of another medicament active ingredient. The kit contains appropriate containers such as boxes, bottles, sachets or individual ampoules. The kit may contain, eg, separate ampoules containing, each one, an effective amount of a compound of formula I and / or its derivatives, solvates and stereoisomers of pharmaceutical utility, including mixtures thereof in all of them. the proportions, and an effective amount of another active drug substance dissolved or in lyophilized form Another object of the invention is, furthermore, the use of compounds of formula I and / or their derivatives, solvates and stereoisomers of pharmaceutical utility.; including their mixtures in all proportions, for the preparation of a drug for the treatment of thrombosis, myocardial infarction, arteriesclerosis, inflammation, stroke, angina pectoris, post-angioplasty restenosis, claudicatio intermittens, migraine, tumors, tumoral diseases and / or tumor metastasis, in combination with at least one other active drug ingredient. Previously and subsequently, all temperatures are indicated in ° C. In the examples below, "conventional processing" means that, if necessary, water is added, if necessary, depending on the constitution of the final product, at pH values between 2 and 10, it is ex-brought with Ethyl acetate or dichloromethane is separated, the organic phase is dried over sodium sulfate, evaporated and purified by chromatography on silica gel and / or by crystallization Rf values on silica gel, eluent: acetate Ethyl / methanol 9: 1. Mass spectrometry (MS): The (ionization by means of electric impact) M * ESI (ionization by electronebulization) (M + H) + FAB (fast atom bombardment) (M + H) + Use 1 The preparation of (R) -1- (4-chloro-f-enyl) -3- [2- (1 '-methyl- [4, 4'] -bipiperidinyl-1-yl) -2 -oxo-l-enyl-ethyl] -urea (1) is carried out according to the following scheme: 1. 1 Preparation of (R) - [2- (1-methyl- [4,4 '] bipiperidinyl-l-yl) -2-oxo-l-f-ethyl] -carbamic acid tert-butyl ester 3.28 g (11.06 mmol) of 1-methyl- [4, 4 'Jbipiperidinyl are dissolved together with 2.78 g (11.06 mmol) of (R) -Boc-f-enylglycine, 2.33 g ( 12.17 mmol) of (N- (3-dimethylaryl propyl) -N'-ethylcarbodiimide hydrochloride (DAPECI) and 1.86 g (12.17 mmol) of hydroxybenzotriazole hydrate in 30 ml of dimethylformamide and mixed with 4 ml of 4-methylmorpholine After 24 hours, the reaction mixture is worked up in a conventional manner to obtain 1.8 g of (R) - [2- (1'-? Tetyl) -butyl butyl ester. [4,4 '] bipiperidinyl-l-yl) -2-oxo-l-enyl-ethyl] -carbamic acid 1.2 Preparation of (1-methyl- [4,4'] bipiperidinyl-1-yl) -amide trifluoroacetate of (R) -2-amino-2-f-enyl-acetic acid 1.8 g (4.33 mmol) of (R) - [2- (1'-methyl-4-butyl- [4] -butyl ester are dissolved. , 4 '] bi? Iperidinyl-1-yl) -2-oxo-l-phenyl-ethyl] -carbamic acid in 30 ml of trifluoroacetic acid 20% in dichloromethane and stirred for 2 hours. quantitatively trifluoroace (1'-methyl- [4,4 '] bipiperidixyl-1-yl) -amide of (R) -2-amino-2-f-enyl-acetic acid. 1.3 0.93 g (1.02 mmol) of trifluoroacetate of (R) -2-amino-2-phenyl (1-methyl- [4,4 '] bipiperidinyl-1-yl) -amide is dissolved. -acetic together with 165 mg (1.07 mmol) of 4-chlorophenylisocyanate, adding 0.9 ml of triethylamine in 50 ml of dichloromethane and stirring for 24 h.

After the usual working-up and chromatography, 250 mg of (R) -1- (4-chloro-f-enyl) -3- [2- (1-methyl- [4,4 '] bipiperidinyl-1-yl are isolated) -2-oxo-lf enyl-ethyl] -urea (1), ESI 470. Analogously, the following compounds are obtained (R) -1- (4-chloro-f-enyl) -3-. { 2- [4- (4-f luoro-f-enyl) -piperazin-1-yl] -2-oxo-l-phenyl-ethyl} -urea (2), ESI 467; (R) -1- (4-chloro-phenyl) -3-. { 2- [4- (4-f luoro-f-enoxy) -piperidin-1-yl] -2-oxo-l-phenyl-ethyl} -urea (3), ESI 482; bis (R) -l- (4-chloro-phenyl) -3- [2-oxo-l-phenyl-2- (4-pyridin-4-yl-piperazin-1-yl) -ethyl] bis-trifluoroacetate - urea (4), ESI 450; (R) -l- (4-chloro-phenyl) -3- bis-trifluoroacetate. { 2- [4- (1-methyl-piperidin-4-yl) -piperazin-1-yl] -2-oxo-1-phenyl-ethyl} -urea (5), ESI 471; (R) -1- (4-chloro-phenyl) -3- bis-trifluoroacetate. { 2- [4- (4-ethyl-piperazin-1-yl) -piperidin-1-yl] -2-oxo-l-f-enyl-ethyl} -urea (6), ESI 485; (R) -l- (4-Chloro-phenyl) -3- [2-oxo-l-phenyl-2- (4-pyridin-3-ylmethylpiperazin-1-yl) -ethyl] -urea bis-trifluoroacetate ( 7), ESI 464; bis-trifluoroacetate of (R, R) -1- (4-chloro-f-enyl) -3-. { 2-methoxy-1- [1- (4-pyridin-4-yl-piperazin-1-yl) -methanoyl] -propyl} -urea (8), ESI 432; bis (trifluoroacetate) of (R, R) -1- (4-chloro-f-enyl) -3- (2-methoxy-l-. {l- [4- (l-methyl-piperidin-4-yl) - piperazin-1-yl] -methanoyl.}. -propyl) -urea (9), ESI 453 trifluoroacetate of (R, R) -1- (4-chloro-phenyl) -3-. { 2-methoxy-1- [1- (1-methyl [4,4 '] bipiperidinyl-1-yl) -methanoyl] -propyl} -urea (10), ESI 452; (R) -1- (4-Chloro-phenyl) -3- [2-oxo-l-phenyl-2- (4-pyridin-4-yl-piperazin-1-yl) -ethyl] -urea (11) , ESI 450; (R) -1- (4-Chloro-phenyl) -3- [1- (4-pyridin-4-yl-piperazine-1-carbonyl) -butyl] -urea (12), ESI 416; (R) -1- (4-chloro-phenyl) -3-. { 2- [4-hydroxy-4- (4-methoxy-phe nyl) -piperidin-1-yl] -2-oxo-l-phenyl-ethyl} -urea (13), ESI 477; (R) -1- (4-chloro-phenyl) -3-. { 2- [4- (2-methoxy-phenyl) -piperazin-1-yl] -2-oxo-l-phenyl-ethyl} -urea (14), ESI 479; (R) -N- [4- (l- { 2- [3- (4-chloro-phenyl) -ureido] -2-phenyl-ethanoyl} - piperidin-4-ylmethyl) -phenyl ] -acetamide (15), ESI 510; (R) -1- (4-chloro-phenyl) -3-. { 2-oxo-l-phenyl-2- [4- (1-phenyl-methanoyl) -piperidin-1-yl] -ethyl} -urea (16); ESI 476; (R) -1- (4-Chloro-phenyl) -3- [2-oxo-l-phenyl-2- (4-pyridin-2-yl-piperazin-1-yl) -ethyl] -urea (17) , ESI 450; (R) -1- [2- (4-Benzyl-piperazin-1-yl) -2-oxo-l-f-enyl-ethyl] -3- (4-chloro-phenyl) -urea (18), ESI 463; (R) -1- (4-chloro-f-enyl) -3-. { 2- [5- (4-f luoro-f-enyl) -2,5-diaza-bicyclo [2.2.1] hept-2-yl] -2-oxo-l-phenyl-ethyl} -urea (19), ESI 479 (R) -1- (4-chloro-phenyl) -3-. { 2- [4- (4,6-Dimethyl-pyrimidin-2-yl) -piperazin-1-yl] -2-oxo-1-phenyl-ethyl} -urea. (20), ESI 479; (R, S) -1- [2- (3-benzyl-piperidin-1-yl) -2-oxo-1-phenyl-ethyl] -3- (4-chlorophenyl) -urea (21), ESI 463; (S, S) -1- (4-chloro-phenyl) -3-. { 2-hydroxy-l- [1- (4-pyridin-4-yl-piperazin-1-yl) -methanoyl] -propyl} -urea (22), ESI 418; (S, S) -1- (4-chloro-f-enyl) -3- (2-hydroxy-l- { L- [4- (1-methyl-piperidin-4-yl) -piperazin-1- il] -methanoyl.}. -propyl) -urea (23), ESI 438; bis-trifluoroacetate of (R, R) -1- (4-chloro-phenyl) -3-. { 2-methoxy-1- [1- (4-pyridin-3-ylmethyl-piperazin-1-yl) -methanoyl] -propyl} -urea (24), ESI 446; (R) -1- (4-chloro-f-enyl) -3- [2-oxo-l-phenyl-2- (4-pyridin-4-yl-piperazin-1-yl) -ethyl] bis-trifluoroacetate] -urea (25), ESI 450; bis-trifluoroacetate of (R, R) -1- (4-chloro-phenyl) -3- (1- {1- [4- (4-ethyl-pipera-zin-1-yl) -piperidin-1) -yl] -methanoyl.} -2-methoxy-propyl) -urea (26), ESI 467; (R) -l- (4-chloro-phenyl) -3- bis-trifluoroacetate. { 2- [4- (1-methyl-piperidin-4-yl) -piperazin-1-yl] -2-oxo-1-phenyl-ethyl} -urea (27), ESI 471; (R) -l- (2- [4,4 '] bipiperidinyl-l-yl-2-oxo-l-phenyl-ethyl) -3- (4-chloro-enyl) -urea hydrochloride (28), ESI 456; (R) -l- [2- [4,4 '] bipiperidinyl-l-yl-l- (4-hydroxy-phenyl) -2-oxo-ethyl] -3- (4-chloro-phenyl) -hydrochloride urea (29), ESI 472; (R) -1- (2- [4,4 '] bipiperidinyl-l-yl-2-oxo-l-thiophen-2-yl-ethyl) -3- (4-chloro-phenyl) -urea hydrochloride ( 30), ESI 462; (R) -1- (4-chloro-f-enyl) -3- [1- (4-hydroxy-f-enyl) -2- (1 '-methyl [4,4'] bipiperidinyl-l-yl trifluoroacetate) -2-oxo-ethyl] -urea (31), ESI 486; (R) -1- (4-chloro-phenyl) -3- [2- (1-methyl- [4,4 '] bipiperidinyl-l-yl) -2-oxo-l-thiof en-2 trifluoroacetate -yl-ethyl] -urea (32), ESI 476; (R) -l- (4-chloro-phenyl) -3- [l- (4-hydroxy-phenyl) -2- (4-morpholin-4-yl-piperidin-l-yl) -2-oxo trifluoroacetate -ethyl] -urea (33), ESI 473; 1- [2- [1, 4 '] bipiperidinyl-1-yl-1- (4-hydroxy-phenyl) -2-oxo-ethyl] -3- (4-chloro-phenyl) -urea, trifluoroacetate of ( R) -l- (4-chloro-phenyl) -3- [2- (4-morpholin-4-yl-piperidin-1-yl) -2-oxo-l-phenyl-ethyl] -urea (35), ESI 457; (R) -l- (2- [1, 4 '] bipiperidinyl-1-yl-2-oxo-l-phenyl-ethyl) -3- (4-chloro-phenyl) -urea trifluoroacetate (36), ESI 456; (R) -l- (4-chloro-phenyl) -3- [2- (4-cyclohexyl-piperazin-1-yl) -l- (4-hydroxy-phenyl) -2-oxo-ethyl] trifluoroacetate] - urea (37), ESI 471; (R) -l- (4-chloro-phenyl) -3- [2- (4-cyclohexyl-piperazin-1-yl) -2-oxo-l-phenyl-ethyl] -urea trifluoroacetate (38), ESI 456; (R) -l- (4-chloro-phenyl) -3- bis-trifluoroacetate. { 1- (4-hydroxy-phenyl) -2- [4- (4-methyl-piperazin-1-yl) -piperidin-1-yl] -2-oxo-ethyl} -urea (39), ESI 487; (R) -l- (4-chloro-phenyl) -3- bis-trifluoroacetate. { 2- [4- (4-methyl-piperazin-1-yl) -piperidin-1-yl] -2-oxo-1-phenyl-ethyl} -urea (40), ESI 471; (R) -l- (4-chloro-phenyl) -3- [2- (4-morpholin-4-yl-piperidin-1-yl) -2-oxo-l-thiophen-2-yl-ethyl trifluoroacetate ] -urea (41), ESI 464; (R) -l- (2- [1, 4 '] bipiperidinyl-1-yl-2-oxo-l-thiophen-2-yl-ethyl) -3- (4-chloro-phenyl) -urea trifluoroacetate (42), ESI 462; (R) -l- (4-Chloro-phenyl) -3- [2- (4-cyclohexyl-piperazin-1-yl) -2-oxo-l-thiophen-2-yl-ethyl] -urea trifluoroacetate ( 43), ESI 462; (R) -l- (4-chloro-phenyl) -3- bis-trifluoroacetate. { 2- [4- (4-Methyl-piperazin-1-yl) -piperidin-1-yl] -2-oxo-1-thiophen-2-yl-ethyl} -urea (44), ESI 477; (R) -1- (4-chloro-f-enyl) -3- [2- (1-methyl- [4, 4 '] bipiperidinyl-1-yl) -2-oxo-1- (2-chlorofenyl) ) -ethyl] -urea (45), (R) -1- (4-chloro-phenyl) -3- [2- ([4,4 '] bipiperidinyl-l-yl) -2-oxo-l- ( 2-chloro-enyl) -ethyl] -urea (46), (R) -1- (4-chloro-f-enyl) -3- [1- (2-chloro-f-enyl) -2- (1'-methyl) -2 '-oxo- [4, 4'] bipiperidinyl-1-yl) -2-oxo-ethyl] -urea (47) (R) -1- (4-chloro-phenyl) -3- [1-phenyl-2- (1'-methyl-2'-oxo- [4, 4 '] bipiperidinyl-1-yl) -2-oxo -ethyl] -urea (48). Example 2 The preparation of 2- (1-methyl- [4, 'Jbipiperidinyl-1-yl) -2-oxo-1-phenyl-ethyl ester of (R) - (4-chloro-phenyl) -carbamic acid (49) is carried out analogously to the following scheme: 2. 1 Preparation of (R) - (2-Chloro-f-enyl) - (4-chloro-phenylcarbamoyl-oxy) -acetic acid 1 g (5 mmol) of (R) - (2-chloro-phenyl) - is dissolved hydroxy acetic acid in 10 ml of dichloromethane and successively mixed with 0.77 g (5 mmol) of 4-chlorophenylisocyanate and 50 mg of dibutyltin dilaurate and stirred for 16 hours. After working up in the usual manner, 1.5 g of (R) - (2-chloro-phenyl) - (4-chloro-f-enylcarbamoyloxy) -acetic acid are obtained. 2.2 92 mg (0.5 mmol) of 1-methyl- [4,4 '] bipiperidinyl are dissolved together with 170 mg (0.5 mmol) of acid (R) - (2-Chloro-phenyl) - (4-chloro-f-enylcarbamoyloxy) -acetic acid, 124 mg (0.65 mmol) of (N- (3-dimethylaminopropyl) -N'-ethylcarbodiimide hydrochloride (DAPECI) and 100 mg (0.65 mmol) of hydroxybenzotriazole hydrate in 2 ml of dimethylformamide and mixed with 72 μl of 4-methylmorphine, after 24 hours, the reaction mixture is worked up in the usual manner. , 15 mg of trifluoroacetate of 2- (1'-methyl- [4,4 '] bipiperidinyl-l-yl) -2-oxo-l-ethyl-ethyl ester of (R) -4-chloro-phenyl) trifluoroacetate are obtained carbamic (49), ESI 471. Analogously the following compounds are obtained 2-oxo-l-enyl-2- (4-pyridin-4-yl-piperazin-1-yl) -ethyl ester of (R) - ( 4-chloro-f-enyl) -carbamic acid (50), ESI 451; 2- [4,4 '] Bipiperidinyl-l-yl-l- (2-chloro-phenyl) -2-oxo-ethyl ester hydrochloride of (R) - (4-chloro-phenyl) -carbamic acid (51) ., ESI 491; 2- [4,4 '] bipiperidinyl-l-yl-2-oxo-l-phenyl-ethyl ester hydrochloride of (R) - (4-chloro-f-enyl) -carbamic acid (52), ESI 456; 1- (2-Chloro-phenyl) -2- (1-methyl- [4, 4 '] bipiperidinyl-1-yl) -2-oxo-ethyl ester trifluoroacetate of (R) - (4-chloro- phenyl) -carbamic (53), ESI 505; 1- (2-chloro-phenyl) -2- (4-morpholin-4-yl-piperidin-1-yl) -2-oxo-ethyl ester trifluoroacetate of (R) - (4-chloro-phenyl) - carbamic (54), ESI 493; 2- (1,4 ') Bipiperidinyl-1-yl-1- (2-chloro-f-enyl) -2-oxo-ethyl ester of (R) - (4-chloro-f-enyl) -carbamic acid trifluoroacetate (55), ESI 491; 2- (4-morpholin-4-yl-piperidin-1-yl) -2-oxo-1-phenyl-ethyl ester trifluoroacetate of (R) - (4-chloro-f-enyl) -carbamic acid (56), ESI 458; 2- (1,4'-Bipiperidinyl-1-yl-2-oxo-l-phenyl-ethyl) -trifluoroacetate of (R) - (4-chloro-f-enyl) -carbamic acid (57), ESI 456; 1- (2-chloro-f-enyl) -2- (4-cyclohexyl-piperazin-1-yl) -2-oxo-ethyl ester of (R) - (4-chloro-phenyl) -carbamic acid ester (58) ), ESI 491; 2- (4-cyclohexyl-piperazin-1-yl) -2-oxo-1-phenyl-ethyl ester trifluoroacetate of (R) - (4-chloro-f-enyl) -carbamic acid (59), ESI 456; 1- (2-Chloro-phenyl) -2- [4- (4-methyl-piperazin-1-yl) -piperidin-1-yl] -2-oxo-ethyl ester of the (R) - acid ester bis-trifluoroacetate (4-chloro-f-enyl) -carbamic (60), ESI 506; 2- (4- (4-Methyl-piperazin-1-yl) -piperidin-1-yl] -2-oxo-1-phenyl-ethyl ester bis-trifluoroacetate of (R) - (4-chloro-phenyl) ) -carbámico (61), ESI 472; 1- (2, 3-difluoro-f-enyl) -2- (1 '-methyl- [4, 4' Jbipi-peridinyl-1-yl) -2-oxo-ethyl ester of (R) - (4 -chloro-phenyl) -carbamic acid (62), ESI 507; 1- (2-f luoro-f-enyl) -2- (1 '-methyl [4, 4'] bipiperidinyl-l-yl) -2-oxo-ethyl ester of (R) - (4-chloro-phenyl) ) -carbámico (63), ESI 489; 1- (2-methyl-oxy-phenyl) -2- (4- (4,4 ') bipiperidinyl-1-yl) -2-oxo-ethyl ester of (R) ~ (4-chloro-f) enil) -carbamic (64), ESI 501. Pharmacological data (affinity for receptors) The following examples refer to medicaments: Example A: Blisters for injection A solution of 100 g of an active ingredient of formula I and 5 g of disodium hydrogen phosphate in 3 1 of bidistilled water is adjusted to a pH value 6.5 using 2N hydrochloric acid, filtered in sterile form, transferred to ampoule bottles for injection, freeze-dried under sterile conditions and sealed in sterile form. Each vial-ampoule for injection contains 5 mg of active ingredient.

Example B: Suppositories A mixture of 20 g of an active ingredient of the formula I is melted with 100 g of soya lecithin and 1400 g of cocoa butter, poured into molds and allowed to cool. Each su-positorio contains 20 mg of active ingredient. Example C: Solution A solution of 1 g of an active ingredient of the formula I, 9.38 g of NaH2P04 • 2 H20, 28.48 g of Na2HP0 • 12 H20 and 0.1 g of benzalkonium chloride in 940 is prepared ml of bidistilled water. The solution is adjusted to a pH of 6.8, completed to 1 1 and sterilized by irradiation. This solution can be used in the form of ophthalmic drops. Example D: Ointment 500 mg of an active ingredient of formula I are mixed with 99, 5 g of Vaseline under aseptic conditions. Example E: Tablets A mixture of 1 kg of active ingredient of the formula I, 4 kg of lactose, 1.2 kg of potato starch, 0.2 kg of talc and 0.1 kg of magnesium stearate is compressed in a manner conventional for forming tablets, such that each tablet contains 10 mg of active ingredient. Example F: Coated tablets Analogously to Example E, the tablets are pressed and then coated conventionally with a cover of saccharose, potato starch, talc, gum tragacanth and dye.

Example G: Capsules 2 kg of active ingredient of the formula I are placed in conventional manner in hard gelatin capsules, so that each capsule contains 20 mg of active ingredient. Example H: Ampoules A solution of 1 kg of active ingredient of the formula I in 60 1 of bidistilled water is sterile filtered, transferred to ampoules, lyophilized under sterile conditions and sealed under sterility. Each ampoule contains 10 mg of active ingredient. It is noted that in relation to this date the best method known by the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (29)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. Compounds of the formula I characterized in that D is an unsubstituted mono- or polysubstituted mono- or polysubstituted carbocycle or heterocycle with Hal, A, OR2, N (R2) 2, N02, CN, COOR2, CON (R2) 2 or -C = CH with 0 to 4 atoms of N, 0 and / or S, X is NR3 or 0, Y is 0, S, NH, N-CN or N-N02, R1 is H, Ar, Het, cycloalkyl or A, which may be mono, di or trisubstituted with OR2, SR2, SYSOP2, S0_N (R2) 2, S03R2, S (= 0) (= NR2) R2, NR2S02R2, OS02R2, OS0N (R2) 2, N (R2) 2, CN, COOR2, CON (R2) 2, Ar, Het or cycloalkyl, E is CH or N, Z is absent or is a (CH_) g group unsubstituted or monosubstituted with carbonyl oxygen (= 0), wherein one or two CH2 groups they may be replaced by N, 0 and / or S atoms and / or by a group -CH = CH-, Z 'is absent or is a (CH_) g' unsubstituted or monosubstituted with carbonyl oxygen (= 0) group , where one or two CH2 groups may be replaced by N, 0 and / or S atoms and / or by a group -CH = CH-, Q is absent, is 0, NR2, C = 0, S02 or C ( R2) n, R2 is H, A, ~ [C (R) 2] n-Ar ', - [C ( R3) 2] nHet ', - [C (R3) 2] n-cycloalkyl, - [C (R3) 2] nN (R3) 2 or - [C (R3) 2] _- 0R3, R3 is H or A , R4, R4 'each, independently of one another, is absent, are A, OH or OA, R4 and R4' are also together methylene or ethylene, T is a mono- or bicyclic saturated, unsaturated or aromatic carbocycle or heterocycle with 0 to 4 atoms of N, 0 and / or S, which may be mono, di or trisubstituted with = 0, = S, = NH, = NR3, = N0R3, = NC0R3, = NC00R3, = N0C0R3, R3, Hal, A, - [C (R3) 2] n- Ar, - [C (R3) 2] n-Het, - [C (R3) 2] n-cycloalkyl, OR3, N (R3) 2, N02, CN, COOR3, CON (R3) 2, NR3C0A, NR3CON (R3) 2, NR3S02A, COR3, S02NR2 and / or S (0) nA, A is unbranched or branched alkyl with 1-10 C atoms, wherein one or two CH2 groups may be replaced by 0 or S atoms and / or by groups -CH = CH- and / or also 1-7 H atoms can be replaced by F, Ar is phenyl, naphthyl or unsubstituted biphenyl or mono, di or trisubstituted with Hal, A, OR2, N (R2 ) 2, N02 / CN, COOR2, CON (R2) 2, NR2COA, NR2S02A, COR2, S02N (R2) 2, - [C (R3) 2] n-COOR2, -0- [C (R3) 2] or -C'00R2, S03H or S (0) nA, Ar 'is unsubstituted phenyl or mono, di or trisubstituted with Hal, A, OR3, N (R3) 2, N02, CN, COOR3, CON (R3) 2, NR3COA , NR3CON (R3) 2, NR3S02A, COR3, S02N (R3) 2, S (0) nA, - [C (R3) 2] n-COOR3 or -0- [C (R3) 2] or-C00R3, Het is a saturated or unsaturated mono or bicyclic heterocycle with 1 to 4 N, 0 and / or S, which may be unsubstituted or mono, di or trisituted with the carbonyl oxygen (= 0), = S,. = N (R2) 2, Hal, A, - [C (R3) 2] n-Ar, - [C (R3) 2] n-Het ', - [C (R3) 2] n-cycloalkyl, - [ C (R3) 2] n-0R2, - [C (R3) 2] n- N (R3) 2, N02, CN, - [C (R3) 2] n-C00R2, - [C (R3) 2] n-CON (R2) 2, - [C (R3) 2] n-NR2COA, NR2CON (R2) 2, - [C (R3) 2] n-NRS02A, COR2, S0N (R2) 2 and / or S ( 0) nA, Het 'is a saturated, unsaturated or aromatic mono or bicyclic heterocycle with 1 to 4 N, 0 and / or S atoms, which may be unsubstituted or mono or disubstituted with carbonyl oxygen, = S, = N (R3) 2, Hal, A, OR3, N (R3) 2, N02, CN, COOR3, CON (R3) 2, NR3C0A, NR3CON (R3) 2, NR3S02A, COR3, S02N (R3) 2 and / or S (0) nA, Hal is F, Cl, Br or I, m is 1 or 2, n is 0, 1 or 2, or is 1, 2 or 3, p is 1, 2, 3, 4 or 5, q, q 'are each, independently of each other, 0, 1, 2, 3 or 4, where at least one of the groups Z or Z 'is present, and 0 <q + q '< 6, as well as their derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
2. 2. Compounds according to claim 1, characterized in that D is phenyl unsubstituted or mono- or disubstituted with Hal, A, OR2 or COOR2, or unsubstituted or mono-substituted pyridyl with Hal, as well as its derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
3. 3. Compounds according to claim 1 or 2, characterized in that D is phenyl monosubstituted with Hal, as well as its derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
4. 4. Compounds according to one or more of claims 1-3, characterized in that R2 is H or A, as well as its derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
5. Compounds according to one or more of claims 1-4, characterized in that T is a saturated, unsaturated or aromatic mono or bicyclic heterocycle with 1 to 2 N, 0 and / or S atoms, which may be unsubstituted or mono or disubstituted with A or carbonyl oxygen (= 0), unsubstituted phenyl or mono, di or trisubstituted with Hal, OR2 or NR2C0A, or an unsubstituted, saturated monocyclic carbocycle, as well as derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
6. 6. Compounds according to one or more of claims 1-5, characterized in that Q is absent, is 0 or CH2, as well as their derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
7. 7 Compounds according to one or more of claims 1-6, characterized in that Ar is unsubstituted phenyl or mono, di or trisubstituted with Hal, A, OR2, NR2C0A, S02A, S02NH2, COOR2 or CN, as well as their derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
8. 8 Compounds according to one or more of claims 1-7, characterized in that Ar is unsubstituted phenyl or mono, di or trisubstituted with Hal, A, OR3 or NR3COA, as well as their derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
9. 9. Compounds according to one or more of claims 1-8, characterized in that R1 is Ar, Het, cycloalkyl or A, which may be monosubstituted with OR2, as well as its derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including its mixtures in all proportions.
10. 10 Compounds according to one or more of claims 1-9, characterized in that R1 is unsubstituted phenyl or mono, di or trisubstituted with Hal, OH or OA, an aromatic monocyclic heterocycle with 1 to 2 atoms N, O and / or S, or A, which may be monosubstituted with OR 3, as well as their derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
11. 11. Compounds according to one or more of claims 1-10, characterized in that Het is a saturated, unsaturated or aromatic mono or bicyclic heterocycle with 1 to 2 N, O and / or S atoms, which may be unsubstituted or mono or disubstituted with A or carbonyl oxygen (= 0), as well as their derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
12. 12. Compounds according to one or more of claims 1-11, characterized in that Y is 0, as well as its derivatives, solvates, salts and stereoisomers of pharmaceutical use, including their mixtures in all proportions.
13. 13. Compounds according to one or more of claims 1-12, characterized in that X is NR3 'or O, R3' is H, as well as its derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
14. Compounds according to one or more of claims 1-13, characterized in that Z, Z 'are ethylene, as well as their derivatives, solvates, salts and stereoisomers of pharmaceutical use, including their mixtures in all proportions.
15. Compounds according to one or more of claims 1-14, characterized in that T is a saturated or aromatic monocyclic heterocycle with 1 to 2 N and / or 0 atoms which may be unsubstituted or mono- or di-substituted with A or oxygen carbonyl (= 0), unsubstituted or mono, di or trisubstituted phenyl with Hal, OH, OA or NHCOA, or an unsubstituted, saturated monocyclic carbocycle, as well as its derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including mixtures thereof, all proportions.
16. 16. Compounds according to one or more of claims 1-15, characterized in that A is unbranched or branched alkyl with 1-10 C atoms, wherein 1-7 H atoms can be replaced by F, as well as their derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
17. 17. Compounds according to one or more of claims 1-16, characterized in that D is unsubstituted phenyl or mono or disubstituted with Hal, A, OR2 or COOR2, or unsubstituted or mono-substituted pyridyl with Hal, X is NR3 or O, Y is O, R1 is Ar, Het, cycloalkyl or A, which may be monosubstituted with OR2, E is CH or N, Z, Z 'are ethylene, Q is absent, is O or CH, R2 is H or A, R3 is H or A, R4, R4' each, so independent of each other, is absent, are A, OH or OA, R4 and R4 'are also together methylene or ethylene, T is a saturated or aromatic monocyclic heterocycle with 1 to 2 N and / or O atoms, which may be unsubstituted or mono or disubstituted with A or carbonyl oxygen (= 0), unsubstituted phenyl or mono, di or trisubstituted with Hal, OH, OA or NHCOA, or an unsubstituted, saturated monocyclic carbocycle, A is unbranched or branched alkyl with 1-10 C atoms, wherein 1-7 H atoms may be replaced by F, Ar is unsubstituted or mono, di or trisubstituted phenyl with Hal, A, OR2, NR2COA, S02A, S02NH2, COOR2 or CN, Het is a saturated, unsaturated or aromatic mono or bicyclic heterocycle with 1 to 2 N, 0 and / or S atoms, which may be unsubstituted or mono or disubstituted with A or carbonyl oxygen ( = 0), Hal is F, Cl, Br or I, p is 1, 2, 3, 4 or 5, as well as their derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
18. 18. Compounds according to one or more of claims 1-17, characterized in that D is phenyl monosubstituted with Hal, X is NR3 'or 0, Y is 0, R1 is phenyl unsubstituted or mono, di or trisubstituted with Hal, OH or OA, an aromatic monocyclic heterocycle with 1 to 2 atoms of N, 0 and / or S, or A which may be monosubstituted with OR3, R3 'is H, E is CH or N, z, Z' are ethylene, Q is absent, is O or CH2, R2 is H or A, R3 is H or A, R4, R4 'each, independently of each other, is au- sent, are A, OH or OA, R4 and R4' methylene or ethylene are also together, T is a saturated or aromatic monocyclic heterocycle with 1 to 2 N and / or 0 atoms, which may be unsubstituted or mono- or di-substituted with A or carbonyl oxygen (= 0), unsubstituted phenyl or mono, di or trisubstituted with Hal, OH, OA or NHCOA, or an unsubstituted, saturated monocyclic carbocycle, A- is unbranched or branched alkyl with 1-10 C atoms, wherein 1-7 H atoms may bereplaced by F, Hal is F, Cl, Br or I, as well as their derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
19. 19. Compounds according to one or more of claims 1-18, characterized in that D is phenyl monosubstituted with Hal, X is NR3 'or O, Y is 0, R1 is thienyl, furyl, unsubstituted or mono, di or trisubstituted phenyl with Hal, OH or OA, or A, which may be monosubstituted with OR3, R3 is H or A, R3 'is H, E is CH or N, Z, Z' are ethylene, Q is absent, O or CH2, R2 is H or A, R3 is H or A, R4, R4 each, independently of each other, is absent, are A, OH or OA, R4 and R4 'are also together methylene or ethylene, T is piperidinyl, piperazinyl, pyridinyl, 2-oxo-piperidin-1-yl, 2-oxo-piperidin-4-yl, 2-oxo-pyrrolidin-1-yl, pyrrolidin-1-yl, 2-oxo-lH-pyridin-1-yl, 3-oxo-morpholin-4-yl, morpholin-4-yl, 4-oxo-lH-pyridin-1-yl, 2,6-dioxo-piperidin-1-yl, 2-oxo-piperazin-1-yl, 2,6-dioxo-piperazin-1-yl, 2,5-dioxo-pyrrolidin-1-yl, 2-oxo-l, 3-oxazolidin-3-yl, pyridazinyl, 3-oxo-2H-pyridazin-2 ilo, 2-caprolactam-l-yl (= 2-oxo-azepan-l-yl), 6-oxo-p iperazin-l-yl, 2-aza-bicyclo [2.2.2] -octan-3-on-2-yl, 5,6-dihydro-lH-pyrimidin-2-oxo-l-yl, 2-oxo- [ 1, 3] oxazinan-3-yl or 4H- [1,4] oxazin-4-yl, wherein the radicals may additionally be unsubstituted with A, unsubstituted phenyl or mono, di or trisubstituted with Hal, OH, OA or NHCOA , or an unsubstituted, saturated monocyclic carbocycle, A is unbranched or branched alkyl with 1-10 C atoms, wherein 1-7 H atoms may be replaced by F, Hal is F, Cl, Br or I, as well as its derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
20. 20. Compounds according to one or more of claims 1-19, characterized in that D is phenyl monosubstituted with Hal, X is NR3 'or 0, Y is 0, R1 is thienyl, furyl, unsubstituted phenyl or mono, di- or trisubstituted with Hal, OH or OA, A, which may be monosubstituted with OR, R > is H or A, R3 'is H, E is CH or N, Z is ethylene, Z' is ethylene, Q is absent, is 0 or CH2, R2 is H or A, R3 is H or A, R4, R4 ' is absent, R4 and R4 'are also together methylene or ethylene, T is unsubstituted or mono-substituted piperidin-1- or -4-yl with A and / or carbonyl oxygen (= 0), pyrrazinyl, morpholin-4-yl or unsubstituted cyclohexyl, A is unbranched or branched alkyl with 1-10 C atoms, wherein 1-7 H atoms may be replaced by F, Hal is F, Cl, Br or I, as well as their derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
21. 21. Compounds according to claim 1 (R) -l- (4-chloro-phenyl) -3- [2- (1-methyl- [4,4 '] bipi-peridinyl-1-yl) -2 -oxo-l-phenyl-ethyl] -urea, (R) -1- (4-chloro-phenyl) -3-. { 2- [4- (4-fluoro-phenyl) -pipe-razin-1-yl] -2-oxo-l-phenyl-ethyl} -urea, (R) -1- (4-chloro-phenyl) -3-. { 2- [4- (4-Fluoro-phenoxy) -piperidin-1-yl] -2-oxo-1-phenyl-ethyl} -urea, bis (trifluoroacetate) of (R) -1- (4-chloro-phenyl) -3- [2-oxo-l-phenyl-2- (4-pyridin-4-yl-piperazin-1-yl) - ethyl] -urea, (R) -1- (4-chloro-phenyl) -3- bis-trifluoroacetate. { 2- [4- (l-Methyl-piperidin-4-yl) -piperazin-1-yl] -2-oxo-l-f-enyl-ethyl} -urea, (R) -l- (4-chloro-phenyl) -3- bis-trifluoroacetate. { 2- [4- (4-ethyl-piperazin-1-yl) -piperidin-1-yl] -2-oxo-l-f-enyl-ethyl} -urea, bis (trifluoroacetate) of (R) -l- (4-chloro-phenyl) -3- [2-oxo-l-phenyl-2- (4-pyridin-3-ylmethyl-piperazin-1-yl) - ethyl] -urea, bis (trifluoroacetate) of (R, R) -l- (4-chloro-phenyl) -3-. { 2-methoxy-l- [1- (4-pyridin-4-yl-piperazin-1-yl) -methanoyl] -propyl} -urea, bis-trifluoroacetate of (R, R) -l- (4-chloro-phenyl) -3- (2-methoxy-l- { l- [4- (l-methyl-piperidin-4-yl ) -piperazin-1-yl] -methanoyl.}. -propyl) -urea, trifluoroacetate of (R, R) -l- (4-chloro-f-enyl) -3-. { 2-methoxy-1- [1- (1-methyl [4,4 '] bipiperidinyl-1-yl) -methanoyl] -propyl} -urea, (R) -l- (4-chloro-phenyl) -3- [2-oxo-l-phenyl-2- ('4-pyridin-4-yl piperazin-1-yl) -ethyl] -urea , (R) -1- (4-chloro-phenyl) -3- [1- (4-pyridin-4-yl-piperazin-1-carbonyl) -butyl] -urea, (R) -1- (4- chloro-phenyl) -3-. { 2- [4-hydroxy-4- (4-methoxy-phenyl) -piperidin-1-yl] -2-oxo-l-phenyl-ethyl} -urea, (R) -1- (4-chloro-phenyl) -3-. { 2- [4- (2-methoxy-phenyl) -piperazin-1-yl] -2-oxo-l-phenyl-ethyl} -urea, (R) -N- [4- (l- { 2- [3- (4-chloro-phenyl) -ureido] -2-phenyl-ethanoyl}. -piperidin-4-ylmethyl) - phenyl] -acetamide, (R) -1- (4-chloro-phenyl) -3-. { 2-oxo-l-phenyl-2- [4- (1-phenyl-methanoyl) -piperidin-1-yl] -ethyl} -urea, (R) -1- (4-chloro-phenyl) -3- [2-oxo-l-phenyl-2- (4-pyridin-2-yl-piperazin-1-yl) -ethyl] -urea , (R) -1- [2- (4-benzyl-piperazin-1-yl) -2-oxo-l-phenyl-ethyl] -3- (4-chloro-phenyl) -urea, (R) -1 - (4-chloro-f-enyl) -3-. { 2- [5- (4-f luoro-f-enyl) -2,5-diazabicyclo [2.2. l] hept-2-yl] -2-oxo-l-f-enyl-ethyl} -urea, (R) -1- (4-chloro-phenyl) -3-. { 2- [4- (4,6-Dimethyl-pyrimidin-2-yl) -piperazin-1-yl] -2-oxo-l-phenyl-ethyl} -urea, (R, S) -1- [2- (3-benzyl-piperidin-1-yl) -2-oxo-1-phenyl-ethyl] -3- (4-chloro-phenyl) -urea, ( S, S) -1- (4-chloro-f-enyl) -3-. { 2-hydroxy-l- [1- (4-pyridin-4-yl-piperazin-1-yl) -methanoyl] -propyl} -urea, (S, S) -1- (4-chloro-f-enyl) -3- (2-hydroxy-l- { l- [4- (1-methyl-piperidin-4-yl) -piperazin -1-yl] -methanoyl.}. -p'propyl) -urea, bis-trifluoroacetate of (R, R) -1- (4-chloro-f-enyl) -3-. { 2-methoxy-1- [1- (4-pyridin-3-ylmethyl-piperazin-1-yl) -methanoyl] -propyl} -urea, (R) -1- (4-chloro-f-enyl) -3- [2-oxo-l-phenyl-2- (4-pyridin-4-yl-piperazin-1-yl) bis-trifluoroacetate - ethyl] -urea, bis (trifluoroacetate) of (R, R) -1- (4-chloro-phenyl) -3- (1- {1- [4- (4-ethyl-piperazin-1-yl) - piperidin-1-yl] -methanoyl.} -2-methoxy-propyl) -urea, (R) -1- (4-chloro-phenyl) -3- bis-trifluoroacetate. { 2- [4- (L-methyl-piperidin-4-yl) -piperazin-1-yl] -2-oxo-l-f-enyl-ethyl} -urea, (R) -1- (2- [4, '] bipiperidinyl-l-yl-2-oxo-1-f-enyl-ethyl) -3- (4-chloro-f-enyl) -urea hydrochloride, (R) -1- [2- [4, 4 '] bipiperidinyl-l-yl-l- (4-hydroxy-phenyl) -2-oxo-ethyl] -3- (4-chloro-phenyl) hydrochloride ) -urea, (R) -1- (2- [4, '] hydrochloride bipiperidinyl-l-yl-2-oxo-1-thiof en-2-yl-ethyl) -3- (4-chloro-f) enyl) -urea, (R) -l- (4-chloro-phenyl) -3- [1- (4-hydroxy-phenyl) -2- (1 '-methyl [4,4'] bipiperidinyl-1-trifluoroacetate] -yl) -2-oxo-ethyl] -urea, (R) -1- (-chloro-f-enyl) -3- [2- (1 '-methyl- [4, 4'] bipiperidinyl-1-trifluoroacetate] il) -2-oxo-l-thiophen-2-yl-ethyl] -urea, (R) -l- (4-chloro-phenyl) -3- [l- (4-hydroxy-phenyl) -2- (4-morpholin-4-yl-piperidin-1-yl) -2-trifluoroacetate -oxo-ethyl] -urea, 1- [2- [1,4 '] bipiperidinyl-1' -yl-1- (4-hydroxy-f-enyl) -2-oxo-ethyl] -3- (4-chloro) phenyl) -urea, (R) -1- (4-chloro-phenyl) -3- [2- (4-morpholin-4-yl-piperidin-1-yl) -2-oxo-l-enyl trifluoroacetate -ethyl] -urea, (R) -1- (2- [1,4 '] bipiperidinyl-l' -yl-2-oxo-l-enyl-ethyl) -3- (4-chloro-f-enyl) trifluoroacetate -urea, (R) -1- (4-chloro-f-enyl) -3- [2- (4-cyclohexyl-piperazin-1-yl) -l- (4-hydroxy-phenyl) -2-trifluoroacetate -oxo-ethyl] -urea, (R) -1- (4-chloro-phenyl) -3- [2- (4-cyclohexyl-pi? erazin-1-yl) -2-oxo-lf-trifluoroacetate ethyl] -urea, (R) -1- (4-chloro-f-enyl) -3- bis-trifluoroacetate. { 1- (4-hydroxy-f-enyl) -2- [4- (4-methyl-piperazin-1-yl) -piperidin-1-yl] -2-oxo-ethyl} -urea, (R) -l- (4-chloro-phenyl) -3- bis-trifluoroacetate. { 2- [4- (4-methyl-piperazin-1-yl) -piperidin-1-yl] -2 -oxo-l-f-enyl-ethyl} -urea, (R) -1- (4-chloro-f-enyl) -3- [2- (4-mor-folin-4-yl-piperidin-l-yl) -2-oxo-l-thiofluoroacetate en-2-yl-ethyl] -urea, (R) -1- (2- [1,4'-] bipiperidinyl-l '-yl-2-oxo-l-thiof en-2-yl-ethyl trifluoroacetate) -3- (4-chloro-f-enyl) -urea, (R) -1- (4-chloro-phenyl) -3- [2- (4-cyclohexyl-piperazin-1-yl) -2-oxo trifluoroacetate -l-thiophen-2-yl-ethyl] -urea, (R) -l- (4-chloro-phenyl) -3- bis-trifluoroacetate. { 2- [4- (4-Methyl-piperazin-1-yl) -piperidin-1-yl] -2-oxo-l-thiof en-2-yl-ethyl} -urea, (R) -1- (4-chloro-f-enyl) -3- [2- (1 '-methyl- [4,'] bipiperi-dinyl-1-yl) -2-oxo-l- ( 2-chloro-enyl) -ethyl] -urea, (R) -1- (4-chloro-f-enyl) -3- [2- ([, 4 '] bipiperidinyl-l-yl) -2-oxo-1- (2-chloro-enyl) -ethyl] -urea, (R) -i (4-chloro-f-enyl) -3- [1- (2-chloro-f-phenyl) -2- (1-methyl-2) '-oxo [4, 4'] bipiperidinyl-l-yl) -2-oxo-ethyl] -urea, (R) -1- (4-chloro-f-enyl) -3- [1-f-enyl-2-] (1 '-methyl-2' -oxo- [4, 4 '] bipiperidinyl-1-yl) -2-oxo-ethyl] -urea, 2- (1-methyl- [4,4'] bipiperidinyl- ester l-yl) -2-oxo-l-phenyl-ethyl of (R) - (4-chloro-phenyl) -carbamic acid, 2-oxo-l-phenyl-2- (4-pyridin-4-yl) ester (R) - (4-Chloro-phenyl) -carbamic acid piperazin-1-yl) ethyl ester, 2- [4,4 '] bipiperidinyl-1-yl-1- (2-chloro-phenyl) ester hydrochloride (R) - (4-chloro-phenyl) -carbamic acid-2-oxo-ethyl, 2- [4,4 '] bipiperidinyl-l-yl-2-oxo-1-phenyl-ethyl ester hydrochloride of acid (R) - (4-chloro-f-enyl) -carbamic, ester trifluoroacetate 1- (2 -chloro-phenyl) -2- (4'-methyl- [4,4 '] bipiperidinyl-1-yl) -2-oxo-ethyl of (R) - (4-chloro-phenyl) -carbamic acid, 1- (2-chloro-f-enyl) -2- (4-morpholin-4-yl-piperidin-1-yl) -2-oxo-ethyl ester trifluoroacetate of (R) - (4-chloro-f-ethyl) ester ) -carbamic, 2- [1,4] bipiperidinyl-1-yl-l- (2-chloro-phenyl) -2-oxo-ethyl ester trifluoroacetate of (R) - (4-chloro-f-enyl) ester -carbamic, 2- (4-morpholin-4-yl-piperidin-1-yl) -2-oxo-1-phenyl-ethyl ester trifluoroacetate of (R) - (4-chloro-f-enyl) -carbamic acid, 2- (1,4 ') Bipiperidinyl-1'-yl-2-oxo-l-phenyl-ethyl ester trifluoroacetate of (R) - (4-chloro-f-enyl) -carbamic acid, ester trifluoroacetate l- ( 2-Chloro-phenyl) -2- (4-cyclohexyl-piperazin-1-yl) -2-oxo-ethyl acid of (R) - (4-chloro-f-enyl) -carbamic acid, ester trifluoroacetate 2- (4 (R) - (4-chloro-f-enyl) -carbamic acid-cyclohexyl-piperazin-1-yl) -2-oxo-1-phenyl-ethyl ester, 1- (2-chloro-phenyl) bis-trifluoroacetate ) -2- [4- (4-m) (R) - (4-chloro-f-enyl) -carbamic acid ethyl-piperazin-1-yl) -piperidin-1-yl] -2-oxo-ethyl ester, bis-trifluoroacetate 2- [4- (4 (R) - (4-chloro-f-enyl) -carbamic acid, ester 1- (2, 3-methyl-piperazin-1-yl) -piperidin-1-yl] -2-oxo-l-phenyl-ethyl ester -dif luoro-f-enyl) -2- (1'-methyl- [4,4 '] bipiperidinyl-l-yl) -2-oxo-ethyl of (R) - (4-chloro-phenyl) -carbamic acid, 1- (2-fluoro-phenyl) -2- (1-methyl- [4, 'Jbipiperidi-nyl-1-yl) -2-oxo-ethyl ester of (R) - (4-chloro-phenyl) acid -carbamic ester 1- (2-methoxy-phenyl) -2- (1-methyl- [4,4'-Jbipiperidi-nyl-1-yl) -2-oxo-ethyl ester of (R) - (4 ~ chloro-phenyl) -carbamic, as well as its derivatives, solvates, salts and stereoisomers of pharmaceutical utility, including their mixtures in all proportions.
22. 22. Process for preparing compounds of the formula I in accordance with claims 1-21, as well as its derivatives, solvates and stereoisomers of pharmaceutical utility, characterized in that a) to prepare compounds of the formula I, wherein X is NH and Y is 0, a composed of 'formula II wherein R1, R4, R4 ', E, Q, T, Z and Z' have the meanings indicated in claim 1, with a compound of the formula III D-N = C = 0 III wherein D has the meaning indicated in claim 1, or b) to prepare compounds of the formula I, wherein X and Y are 0, a compound of the formula IV is reacted wherein W, Y and T have the meaning indicated in claim 1, with a compound of formula V wherein X and Y are 0, L is Cl, Br, I or a free OH group or functionally reactive and R1 and D have the meanings indicated in claim 1 and / or a base or an acid is converted from the Formula I in one of its salts.
23. 23. Compounds of the formula I according to one or more of claims 1 to 21, characterized in that they are used as inhibitors of the coagulation factor Xa.
24. 24. Compounds of the formula I according to one or more of claims 1 to 21, characterized in that they are used as inhibitors of the coagulation factor Vlla.
25. 25. Medicaments characterized in that they comprise at least one compound of the formula I according to one or more of claims 1 to 21 and / or its derivatives, solvates and stereoisomers of pharmaceutical use, including mixtures thereof in all the proportions, as well as eventually excipients and / or adjuvants.
26. 26. Medicaments characterized in that they comprise at least one compound of the formula I according to one or more of claims 1 to 21 and / or its derivatives, solvates and stereoisomers of pharmaceutical utility, including their mixtures in all proportions, and at least another medicated active ingredient.
27. 27. Use of compounds according to one or more of claims 1 to 21 and / or their physiologically safe salts and solvates to prepare a medicament for the treatment of thrombosis, myocardial infarction, arteriosclerosis, inflammations, stroke, angina pectoris, post-angioplasty restenosis, claudicatio intermittens, migraine, tumors, tumor diseases and / or tumor metastasis.
28. 28. Kit characterized in that it consists of separate packages of (a) an effective amount of a compound of formula I in accordance with one or more of claims 1 to 21 and / or its derivatives, solvates and stereoisomers of pharmaceutical utility, including mixtures in all proportions, and (b) an effective amount of another active drug ingredient.
29. 29. Use of compounds of the formula I according to one or more of claims 1 to 21 and / or their derivatives, solvates and stereoisomers of pharmaceutical utility, including their mixtures in all proportions, for preparing a medicament for the treatment of thrombosis, myocardial infarction, arteriosclerosis, inflammations, stroke, angina pectoris, post-angioplasty restenosis, claudicatio intermittens, migraine, tumors, tumor diseases and / or tumor metastasis, in combination with at least one other active drug ingredient.