Phosphono/biaryl substituted dipeptide derivatives

Details Phosphono/biaryl substituted dipeptide derivatives Phosphono/biaryl substituted dipeptide derivatives

1991-05-01

1992-10-13

Lee, Mary C.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Phosphorus containing other than solely as part of an...

514 85, 514 89, 514 90, 514 91, 514 95, 514 99, 540542, 544157, 544337, 546 22, 548413, 549 6, 549218, 558170, 558174, 560 16, 560 41, 562 15, A61K 3702, C07F 938, C07F 940

Patent

active

051551004

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.

REFERENCES:
patent: 4053505 (1977-10-01), Dutra
patent: 4618708 (1986-10-01), Roques et al.
patent: 4721726 (1988-01-01), Berger
patent: 4749688 (1988-06-01), Haslanger et al.
patent: 4939261 (1990-07-01), Ksander
patent: 4963539 (1990-10-01), Delaney
patent: 5021430 (1991-06-01), Ksander
Res. Comm. in Chem. Pathology and Pharmacology vol. 52, 81 (1986).
Medicinal Research Reviews vol. 5 483-531 (1985).

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