New carboxylic acid amides are Factor Xa and serine protease inhibitors, useful for the treatment and prevention of thrombotic disorders, tumors and fibrin-dependent inflammation

摘要

Carboxylic acid amide derivatives (I) and their salts, tautomers and stereoisomers are new. Carboxylic acid amide derivatives of formula (I) and their salts, tautomers and stereoisomers are new. One of m and n = 0 and the other is 1; Ar = phenylene or naphthylene (optionally substituted by F, Cl, Br, CF3, 1-3C alkyl, OH, 1-3C alkoxy, phenyl-(1-3C alkoxy), NH2 or mono- or di(1-3C alkyl)amino, where the phenylene may be substituted by a further F, Cl, Br or 1-3C alkyl group), or thienylene, thiazolylene, pyridinylene, pyrimidinylene, pyrazinylene or pyridazinylene (all optionally substituted by 1-3C alkyl on the carbon structure); R1 = H, 1-3C alkyl (optionally substituted by NH2, mono- or di-(1-3C alkyl)amino, phenyl, naphthyl or heteroaryl), 3-7C cycloalkyl (1-substituted by a 5-7 membered cycloalkyleneiminocarbonyl group), a 4-7 membered cycloalkyleneiminocarbonyl group or phenyl (optionally substituted by F, Cl, Br, CF3, 1-3C alkyl or 1-3C alkoxy); or a 1-3C alkoxy, phenyl-(1-3C alkoxy), heteroaryloxy or heteroaryloxy-(1-3C alkoxy) (where the alkoxy groups may be 2- or 3-substituted by NH2 or mono- or di-(1-3C alkyl)amino); or a 3-7C cycloalkoxy (where a CH2 group in the 3- or 4-position of a 5-7C cycloalkoxy may be replaced by NH, which is itself optionally substituted by arylcarbonyl, arylsulfonyl, 1-3C alkylcarbonyl (where the alkanoyl part may be substituted by amino, or mono- or di-1-3C alkylamino), alkylimino, or 1-3C alkyl (optionally substituted in the 2- or 3-position by NH2 or mono- or di-1-3C alkylamino)); R2 = H, F, Cl, Br, 1-3C alkyl, OH or 1-3C alkoxy; R3 = H or 1-3C alkyl; R4 = H or alkyl optionally substituted by COOH; R5 = CN or amidino optionally substituted by one or two 1-3C alkyl groups. An Independent claim is included for the preparation of (I).