Substituted dipeptides, processes for their preparation and pharmaceutical compositions containing them and their use in the inhibition of enkephalinase.

摘要

The present invention relates to substituted depeptides which are useful in the inhibition of a natural opiate receptor against known as <<enkephalin>>! Disclosed are substituted dipeptides of the formula: <CHEM> and the pharmaceutically acceptable salts thereof, in which R1 is hydrogen; alkyl; halogen loweralkyl; hydroxy loweralkyl; loweralkoxy loweralkyl; aryloxy loweralkyl; amino loweralkyl; loweralkylamino loweralkyl; di-loweralkyl aminoloweralkyl; acylamino loweralkyl; diarylaminoloweralkyl; arylamino loweralkyl; guanidino loweralkyl; heteroaryl; aryl; aralkyl; mercapto loweralkyl; arylthio loweralkyl; loweralkylaralkyl; alkylthio loweralkyl; aralkyloxyalkyl; aralkylthioalkyl; or heteroaryloxyalkyl; wherein the latter 3 radicals may be substituted with halogen, loweralkyl, loweralkoxy, hydroxy, amino, aminomethyl, carboxyl, cyano and/or sulfamoyl; or alkenyl substituted by a heterocyclic group or alkyl substituted by a heterocyclic group, the latter two groups optionally being substituted by one or more groups chosen from loweralkyl, hydroxy, loweralkoxy, amino, loweralkylamino, di-loweralkylamino, acylamino, halogeno, halogenoloweralkyl, cyano and/ or sulfonamido; R2 is -COOH, COO-(loweralkyl), -COO-(aryl lower alkyl), -COO aryl, or the group <CHEM> wherein R10 is hydrogen, lower alkyl or benzyl; and R11 is hydroxy, alkoxy, benzyloxy, lower alkyl, aryl or benzyl; R3 is hydrogen or lower alkyl; <CHEM> wherein q is 0 or 1; R4 and R5 are chosen from the groups defined for R1, <CHEM> in which n is 0 or an integer from 1 to 8 inclusive and m is 2 to 8 inclusive, indolyl (e.g. 3-indolyl), indolylalkyl, (e.g. 3-indolyl