Nonapeptide and decapeptide analogs of LHRH, useful as LHRH antagonists

摘要

Nonapeptide and decapeptide analogs of LHRH which have the formula (I) and the pharmaceutically acceptable salts thereof, wherein: X is a D-alanyl residue wherein one hydrogen on C-3 is replaced by: (a) a carbocyclic aryl-containing radical selected from the group consisting of phenyl substituted with three or more straight chain lower alkyl groups, naphthyl, anthryl, fluorenyl, phenanthryl, biphenylyl and benzhydryl; or (b) a saturated carbocyclic radical selected from the group consisting of cyclohexyl substituted with three or more straight chain lower alkyl groups, perhydronaphthyl, perhydrobiphenylyl, perhydro-2,2-diphenylmethyl, and adamantyl; or (c) a heterocyclic aryl containing radical selected from the group consisting of radicals represented by the following structural formulas: wherein A'' and A' are independently selected from the group consisting of hydrogen, lower alkyl, chlorine, and bromine, and G is selected from the group consisting of oxygen, nitrogen, and sulfur; A is an aminoacyl residue selected from the group consisting of L-pyroglutamyl, D-pyroglutamyl, N-acyl-L-prolyl, N-acyl-D-prolyl, N-acyl-D-tryptophanyl, N-acyl-D-phenylalanyl, N-acyl-D-p-halophenylalanyl, and N-acyl-X wherein X is as defined previously; B is an amino acyl residue selected from the group consisting of D-phenylalanyl, D-p-halophenylalanyl, 2,2-diphenylglycyl, and X wherein X is as defined previously; C is an amino acyl residue selected from the group consisting of L-tryptophanyl, D-tryptophanyl, D-phenylalanyl and X wherein X is as defined above; E is glycinamide or -NH-R1, wherein R1 is lower alkyl, cycloalkyl, fluoro lower alkyl or wherein R2 is hydrogen or lower alkyl; are disclosed. These compounds are LHRH antagonists.