US 5,294,632 A · Phosphono/biaryl substituted dipetide derivatives

Abstract

The invention relates to the N-phosphonomethyl-biaryl substituted dipeptide derivatives of formula I ##STR1## and tetrazole derivatives of the formula Ia ##STR2## 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; 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/or 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.

Claims10

Dependent claims

A compound

of the formula Ia ##STR30## wherein A represents a direct bond, lower alkylene, phenylene or cyclohexylene;
m represents 1 or zero, provided than 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;
heterocyclic aryl represents thienyl, furanyl, pyridyl, pyrrolyl or N-lower alkylpyrrolyl;
a pharmaceutically acceptable mono- or di-ester derivative thereof in which one or two of the acidic hydroxy groups of the phosphono functional group are esterified in form of a mono- or di-pharmaceutically acceptable ester;
or a pharmaceutically acceptable salt thereof.

4 more elements

Dependencies are inferred from the claim text.

Phosphono/biaryl substituted dipetide derivatives

Life of this patent

Phosphono/biaryl substituted dipetide derivatives

Life of this patent

Abstract

Claims10