US 5,155,100 A · Phosphono/biaryl substituted dipeptide derivatives

Abstract

The invention relates to the N-phosphonomethyl-biaryl substituted dipeptide derivatives of formula I ##STR1## wherein A represents a direct bond, lower alkylene, phenylene or cyclohexylene; m represents 1 or zero, provided that m represents 1 when A is a direct bond; R.sub.2 represents hydrogen, hydroxy, lower alkyl, aryl-lower alkyl, C.sub.5 -C.sub.7 -cycloalkyl-lower alkyl, amino-lower alkyl, hydroxyl-lower alkyl, lower alkylthio-lower alkyl, lower alkoxy-lower alkyl, aryl-lower alkylthio-lower alkyl or aryl-lower alkoxy-lower alkyl; biaryl represents phenyl substituted by carbocyclic or heterocyclic aryl; and pharmaceutically acceptable mono-, di- or tri-ester derivatives thereof in which one, two or three of the acidic hydroxy groups of the carboxyl and phosphono functional groups are esterified in form of a mono-, di- or tri- pharmaceutically acceptable ester; and pharmaceutically acceptable amide derivatives thereof wherein the carboxyl group is derivatized in form of a pharmaceutically acceptable amide; and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising said compounds; methods for the preparation of said compounds and for the preparation of intermediates; and methods of treating disorders in mammals which are responsive to the inhibition of neutral endopeptidases by administration of said compounds to mammals in need of such treatment.

Claims21

Dependent claims

A compound of formula I ##STR25## wherein A represents a direct bond, lower alkylene, phenylene or cyclohexylene;

m represents 1 or zero, provided that m represents 1 when A is a direct bond;
R.sub.2 represents hydrogen, hydroxy, lower alkyl, aryl-lower alkyl, C.sub.5 -C.sub.7 -cycloalkyl-lower alkyl, amino-lower alkyl, hydroxy-lower alkyl, lower alkylthio-lower alkyl, lower alkoxy-lower alkyl, aryl-lower alkylthio-lower alkyl or aryl-lower alkoxy-lower alkyl;
biaryl represents phenyl substituted by carbocyclic or heterocyclic aryl;
wherein heterocyclic aryl is selected from the group consisting of thienyl, furanyl, pyridyl, pyrrolyl, and N-(lower alkyl)pyrrolyl or a pharmaceutically acceptable mono-, di- or tri-ester derivative thereof in which one, two or three of the acidic hydroxy groups of the carboxyl and phosphono functional groups are esterified in form of a mono-, di- or tri- pharmaceutically acceptable ester;
or a pharmaceutically acceptable amide derivative thereof wherein the carboxyl group is derivatized in form of a pharmaceutically acceptable amide;
or a pharmaceutically acceptable salt thereof.

3 more elements

Dependencies are inferred from the claim text.

Phosphono/biaryl substituted dipeptide derivatives

Life of this patent

Phosphono/biaryl substituted dipeptide derivatives

Life of this patent

Abstract

Claims21