Amide derivatives

摘要

Peptides of the formula and the salts thereof wherein, when Z is -NH, X is H or an acyl radical, and when Z is a direct link between X and the adjacent C atom, X is H, and wherein m1 is 0 or 1-3, m2 is 1-4, P is H, an alkylthio or aralkylthio group, R1 and R2, which may be the same or different, are H or amino, alkyl or aryl radicals or R1 and R2 may be joined together with the adjacent N-atom to form a heterocyclic radical, and where the indole nucleus may be optionally substituted by one or more alkyl groups, provided that when the indole nucleus is unsubstituted and Z is NH and m1 is 1 and m2 is 2 and R1 and R2 are both H, then P is not methylthio are prepared either by reacting a compound of the formula wherein Q is a radical which together with the adjacent acyl radical forms an activated acid function, or a protected derivative thereof with a tripeptide amide of the formula followed, if necessary, by hydrogenolysis and/or hydrolysis so as to replace any protecting group by H or by acylating a tetrapeptide of the general formula of the products wherein Z is NH with a compound X-Q and optionally removing any protecting groups, or by reacting a compound of the formula with a compound of the formula followed if necessary by removal of any protecting groups, or by reacting an ester of the formula with an amino compound HNR1R2, followed, if necessary by hydrogenolysis and/or hydrolysis so as to replace any protecting groups by H. The 2,4,5-trichlorophenyl esters of N-t-butoxy-carbonyl-4-, -5-, and -6-methyl-DL-tryptophan and indol - 3 - ylacetic 3 - (indol - 3 - yl) propionic and 4 - (indol - 3 - yl) butyric acid; N-carbobenzoxy - b - benzyl L - aspartyl - L - phenylalanine anilide and L-aspartyl-L-phenylalanine anilide; N - carbobenzoxy - b - benzyl - L - aspartyl - L - phenylalanine methylamide and L-aspartyl - L - phenylalanine methylamide; N-carbobenzoxy - L - phenylalanine anilide and L - phenylalanine anilide; N - carbobenzoxy-L-phenylalanine methylamide and L-phenylalanine methylamide acetate; N-benzyloxycarbonyl-b -benzyl - L - aspartyl - L - phenylalanine piperidide and L-aspartyl-L-phenylalanine piperidide; N - carbobenzyloxy - L - phenylalanine piperidide and L-phenylalanine piperidine-HCl; N-t-butyloxycarbonyl - b - alanyl - L - tryptophanyl-L-norleucine hydrazide; N-t-butyoxycarbonyl-b -alanyl - L - tryptophanyl - L - norleucine methyl ester; N - benzyloxycarbonyl - L - tryptophanyl-L-novleucine methyl ester and hydrazide and L - tryptophanyl - L - norleucine methyl ester are prepared as starting materials.