Acylierte Tetrapeptidderivate und deren Salze sowie Verfahren zu deren Herstellung

摘要

Compounds of the formula and their salts, wherein X is an acyl radical (including the acyl radical of an a -amino acid) and Y is a direct link between X and the adjacent N or is an aminoacyl residue containing from 1 to 5 known a -amino acids linked by peptide bonds are prepared either by acylating a tetrapeptide of the formula or of a salt thereof with a derivative of the formula X-Y-OH, wherein the acid function is activated, or a protected derivative thereof, or by means of cyanic acid, or by reacting an acid of the formula wherein the carboxyl function is activated or a protected derivative thereof with a tripeptide of the formula or of a salt thereof, or by reacting an acid of the formula wherein the carboxyl function is activated or a protected derivative thereof with a dipeptide of the formula or a salt thereof and removing from the product of any of the foregoing processes, if necessary, any protecting groups by hydrogenolysis and/or hydrolysis, or by reacting a corresponding alkyl or aralkyl ester with ammonia to form the amide followed by hydrogenolysis and/or hydrolysis so as to replace any protecting groups by H. Starting materials and intermediates prepared are the 2,4,5-trichlorophenyl esters of hippuric, carbobenzyloxypyroglutamic, pyroglutamic acid, t-butoxycarbonyl-b -alanine, p-trifluor-acetyl-aminobenzoic acid, acetyl-b -alanine, Na -carbobenzyloxy - Ne - (4 - chloro - 6 - dimethyl-aminotriazin - 2 - yl) - L - lysine, t - butyloxy-carbonyl - L - alanyl - L - phenylalanyl - L - isoleucylglycine, t - butyloxycarbonyl - S - benzyl-L - homocysteine, L - butyloxycarbonyl - N-methyl - L - alanine, Na - carbobenzyloxy - Ne -t - butyloxycarbonyl - L - lysylglycine, benzoyl-b -alanine, acetyl g -aminobutyric acid, carbobenzyloxy - b - alanine and pivaloyl - b - alanine; t - butyloxycarbonyl - L - alanyl - L - tyrosyl-glycine; t - butyloxycarbonyl - L - tryptophanyl-L-methionine; methyl ester and hydrazide; L-aspartyl-L-phenylalanine methyl ester hydrochloride and its carbobenzyloxy derivative; N-t-butyloxycarbonyl - b - alanyl - L - tryptophanyl-L - methionyl - L - aspartyl - L - phenylalanine methyl ester; L-tryptophanyl-L-methionyl-L-aspartyl - L - phenylalanine methyl ester hydrochloride; t - butyloxycarbonyl - b - alanyl - L-tryptophan methyl ester and hydrazide; L-tryptophanyl-L-methionine methyl ester; t-butyloxycarbonyl - b - alanyl - L - tryptophanyl - L-methionine methyl ester and hydrazide; pivaloyl-b - alanine- Na - carbobenzyloxy - Ne - (t-butyloxycarbonyl)-L-lysylglycine and its methyl ester and Na -carbobenzyloxy-Ne -(4-chloro-6-di-methylaminotriazin-2-yl) -L-lysine. Reference has been directed by the Comptroller to Specification 957,892