BENZODIAZEPINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS THEM

摘要

The present invention relates to benzodiazepine derivatives of the formula I, their pharmaceutically acceptable salts, and to pharmaceutical compositions containing them. In the formula, ring A is aryl, heteroaryl or cycloalkyl, R1 is hydrogen, halogen, nitro, acyl, thiocarbamoyl, cyano, optionally substituted hydroxyl, alkyl, carbamoyl, amino, carboxyl, alkenyl, phosphono, sulfonyl, aryl, heteroaryl, pyrrolidine, piperidine, piperazine, piperazinecarbonyl, amidino or guanidino, rings B and C are aryl, heteroaryl, pyrrolidine, piperidine or piperazine, R2 is hydrogen. , halogen, nitro, cyano, optionally substituted alkyl, hydroxy, acyl, carbamoyl, thiocarbamoyl, amino, amidino, guanidino, pyrrolidine, piperidine, piperazine, aryl, heteroaryl, sulfonyl or piperazinecarbonyl, R3 is hydrogen, halogen, nitro, acyl, cyano, optionally substituted hydroxyl, alkyl, sulfonyl, piperazinecarbonyl, amino, carbamoyl, thiocarbamoyl, pyrrolidine, piperidine, , aryl, heteroaryl, amidino or guanidino ort, R4, R5, R6, R7, R8 and R9 are hydrogen, halogen, cyano, acyl, optionally substituted alkyl, hydroxy, amino, carboxyl, alkenyl, phosphono or heteroaryl, X is alkylene, which is May be interrupted by -NH-, -C (= O) -, -NHC (= O) -, -C (= O) NH- or -NHC (= O) NH-, Z1 and Z2 are hydrogen, halogen, optionally substituted alkyl, hydroxy, thioalkyl, aryl, heteroaryl or carboxyl, or Z 1 and Z 2 may be taken together to form an alkylene chain. The compounds are useful in the prevention and treatment of various diseases associated with activated coagulation factor X. SHE