New N-phenyl-oxalamide derivatives, are factor Xa and factor VIIa inhibitors useful e.g. for treating thrombosis, myocardial infarction, inflammation, angina pectoris or tumor diseases

摘要

N'-Substituted N-phenyl-oxalamide derivatives (I) are new. Oxalamide derivatives of formula (I) and their salts, solvates and stereoisomers are new. R1, R3 = H, A, Ar, -alkyl-Ar, Het, -alk-Het or acyl; R2 = Ar or Het; R4 = H, A, OH, A', OAr, -O-alk-Ar, -O-acyl, COOH, COOA', CONH2, CONHA', CONA'2, CN, NHA', NA'2, NHCH2Ar', NH-acyl or halo; X = Ar, -alkyl-Ar or U; Ar = phenyl, naphthyl or biphenylyl (all optionally substituted (os) by one or more M1); M1 = A', halo, OH, OA', OCHH2Ar, O-acyl, COOH, COOA', CONH2, CONHA', CONA'2, CONHNH2, CH2NH2, CH2NHA', CH2NA'2, CH2CH2NH2, CH2NH-acyl, CN, NH2, NHA', NA'2, NHCH2Ar', NHCOAr', C(=NH)NH2, C(=NH)NH-COOA', SO2CH2R6, SO2NR8R9, 5-oxo-4,5-dihydro-1,2,4-triazol-3-yl or 5-methyl-1,2,4-triazol-3-yl; Ar' = phenyl, naphthyl or biphenylyl (all os by one or more M2); M2 = A', halo, OH, OA', O-acyl, COOH, COOA', CONH2, CONHA', CONA'2, CONHNH2, CH2NH2, CH2NHA', CH2NA'2, CH2CH2NH2, CH2NH-acyl, CN, NH2, NHA', NA'2, C(=NH)NH2, C(=NH)NH-COOA', SO2CH2R6 or SO2NR8R9; Het = mono- or bicyclic aromatic heterocycle with 1-4 N, O and/or S heteroatom(s), os by one or more M3; M3 = as M1 but not C(=NH)NH-COOA'; U = -(CH2)p-SO2-(CH2)n-R6, -(CH2)p-SO2-NR8R9, -(CH2)p-NHSO2-(CH2)n-R6 or N-heterocyclyl of formula , all os by one or more M3; Y = O, S or NR5; or (CH2)m (os by one or more M4 and optionally interrupted by O, S or NR5); M4 = OH, OA', OAr', O-acyl, COOH, COOA', CONH2, CONHA', CONA'2, CN, NH2, NHA', NA'2, NH-CH2Ar', NH-acyl, NHCOAr', C(=NH)NH2 or halo; Z' = O or NR5; or (CH2)m (os by one or more M4); A = 1-8C alkyl (os by one or more M4, optionally having 1 or 2 CH2 groups replaced by O, S and/or CH=CH and additionally os by 1-7 F); A' = 1-8C alkyl; R5 = H, A, Ar, -alk-Ar, Het, CO-T-R6 or SO2-T-R6; or may also be C(=NH)-R7 if Y = NR5; T = direct bond; or 1-5C alkylene, 2-5C alkenylene or 2-5C alkynylene (all os by one or more M4); R6 = H, A, Ar, -alk-Ar or Het; R7 = H, A, Ar, -alk-Ar or NR8R9; R8, R9 = H, A, Ar, -alk-Ar, Het, acyl, Q1 or Q2; or NR8R9 = mononuclear saturated, unsaturated or aromatic heterocycle containing 1-3 N, O and/or S heteroatoms (os by one or more M5); M5 = A', halo, OH, OCH2Ar', OA', O-acyl, COOH, COOA', CONH2, CONHA', CONA'2, CONHNH2, CH2NH2, CH2NHA', CH2NA'2, CH2CH2NH2, CH2NH-acyl, CN, NHA', NA'2, NHCH2Ar', NHCOAr', C(=NH)NH2 or SO2CH2R6; Q1 = cycloalkyl (os by 1 or 2 A'); Q2 = mononuclear saturated or unsaturated heterocycle containing 1-3 N, O and/or S heteroatoms (os by one or more M5); alk = 1-6C alkylene; m = 0-4; n = 1-3; p = 1-5. An Independent claim is included for the preparation of (I).