Anti-hypertensive octahydro-6-azaindole dipeptide derivatives.

摘要

Octahydro-6-azaindole dipeptide derivatives are inhibitors of angiotensin converting enzyme, useful for the treatment of hypertension and have the formula:
<CHEM>
wherein:
R<1> is H, C1-C6 alkyl, C2-C6 alkenyl or aryl-(C1-4 alkyl);
R<2> is C1-C6 alkyl C2-C6 alkenyl, C3-C7 cycloalkyl or substituted C1-C6 alkyl in which the substituent is halo, hydroxy, C1-C6 alkoxy, aryl, aryloxy, aryl-(C1-C4 alkoxy), C3-C7 cycloalkyl, -NR<5>R<6>, -NHCOR<5>, -NHCO2R<7> guanidino, C1-C4 alkylthio, arylthio, aryl-(C1-C4 alkyl)thio or a heterocyclyl group;
R<3> is C1-C6 alkyl, C3-C7 cycloalkyl or a substituted C1-C6 alkyl group in which the substituent is -NHCOR<5>, -NHCO2R<7>, -NR<5>R<6>, hydroxy, halo, -CONR<5>R<6>, C3-C7 cycloalkyl, guanidino, -CO2H, -CO2(C1-C4 alkyl), C1-C4 alkoxy, C1-C4 alkylthio, aryl or a heterocyclyl group;
R<4> is -COR<5>, -CO2R<7>, -SO2R<7>, -SO2NR<5>R<6>, -CONR<5>R<6>, -CON(R<5>)SO2R<7> or -CON(R<5>)COR<7>,
wherein R<5> and R<6> are each independently H, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, heterocyclyl or a substituted C1-C6 alkyl group in which the group is substituted by one or more halo atoms or a hydroxy, C3-C7 cycloalkyl, aryl, heterocyclyl or -NR<8>R<9> group wherein R<8> and R<9> are each independently H, C1-C4 alkyl, -CO(C1-C4 alkyl) or aryl; or the two groups R<5> and R<6> when attached to nitrogen may be taken together with the nitrogen atom to form a pyrrolidinyl, piperidino, morpholino, piperazinyl or N-(C1-C4 alkyl)-piperazinyl group; and R<7> is as defined for R<5> but not including hydrogen.