BENZODIAZEPINE DERIVATIVES AND A PROCESS FOR THE PREPARATION THEREOF

摘要

New racemic or optically active 4-substituted--1,3,4,5-tetrshydro-2H-1, 4-benzodiazepine-2-one derivatives of the general formula (I) (I) wherein R1 stands for hydrogen, halogen, trifluoromethyl, amino or nitro, R2 stands for hydrogen or alkyl, R3 stands for an acyl group derived from a carbonic acid derivative or from an optionally substituted aliphatic, cycloaliphatic or aromatic carboxylic acid, and R6 stands for phenyl or halophenyl, with the proviso that(i) if the compound is racemic, and R2 stands for lower alkyl and R1 stands for hydrogen or halogen, R3 may not stand for a carbamoyl group having a lower alkyl, lower alkenyl, cyclohexyl, phenyl or benzyl substituent, or(ii) if the compound is racemic, and R2 stands for lower alkyl and R1 stands for halogen or trifluoromethyl, R3 may not stand for lower alkanoyl, are prepared as follows: a) a racemic or optically active 1,3,4,5-tetra-hydro-2H-1,4-benzodiazepine-2-one derivative of the general formula (II), (II) wherein R1, R2 and R6 each have the same meanings as defined above, is reacted, optionally in the presence of an acid binding agent, with an acid derivative of the general formula (III), R4 - CO - X , (III) prepared optionally directly in the reaction mixture from the appropriate carboxylic acid, wherein X stands for halogen or alkoxy, and R4 stands for halogen; an optionally substituted aliphatic, cycloalipatic or aromatic hydrocarbyl group or an oxy derivative thereof; amino group; or an amino group having an optionally substituted amino, a hydrocarbyl (as defined above) or an acyl substituent, and, if desired, a thus-ob-tanied compound of the general formula (I), wherein R1, R2 and R6 each have the same meanings as defined above and R3 stands for halocarbonyl, is reacted with ammonia or with an amine; or b) a racemic or optically active 1,3,4,5-tetra-hydro-2H-1,4-benzodiazepine-2-one derivative of the general formula (II), wherein R1, R2 and R6 each have the same meanings as defined above, or a salt thereof is reacted with a compound of the general formula (IV), R5 - Y (IV) wherein R5 stands for hydrogen, alkali metal, or an aliphatic, cycloaliphatic or aromatic hydrocarbyl group and Y stands for a group of the formula NCOor OCN-, and, if desired, any racemic or optically active compound of the general formula (I), wherein R1, R3 and R6 each have the same meanings as defined above and R2 stands for hydrogen, is alkylated. The above compounds possess excellent tranquillo-sedative effects and can be used in the therapy primarily for the treatment of depressive conditions.