Neprilysin inhibitors

Patent metadata

Field	Value
Publication number	US-10315984-B2
Application number	US-201715843427-A
Country	US
Kind code	B2
Filing date	Dec 15, 2017
Priority date	Jun 8, 2012
Publication date	Jun 11, 2019
Grant date	Jun 11, 2019

Abstract

In one aspect, the invention relates to compounds having the formula XII:

where R a , R b , R 2 , R 7 , and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds described herein are prodrugs of compounds having neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising these compounds; methods of using these compounds; and processes and intermediates for preparing these compounds.

First claim

What is claimed is:

1. A compound of:
(a) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[3-(2-fluorophenyl)isoxazole-5-carbonyl]amino}-2-hydroxypentanoic acid;
(b) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[3-(2-fluorophenyl)isoxazole-5-carbonyl]amino}-2-hydroxypentanoic acid ethoxycarbonyloxymethyl ester;
(c) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[3-(2-fluorophenyl)isoxazole-5-carbonyl]amino}-2-hydroxypentanoic acid isopropoxycarbonyloxymethyl ester;
(d) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[3-(2-fluorophenyl)isoxazole-5-carbonyl]amino}-2-hydroxypentanoic acid acetoxymethyl ester;
(e) (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-4-{[3-(2-fluorophenyl)isoxazole-5-carbonyl]amino}-2-hydroxypentanoic acid (S)-2-methoxycarbonylamino-3-methylbutyryloxymethyl ester; or
a pharmaceutically-acceptable salt thereof.

2. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of claim 1 .

3. A method for treating hypertension, heart failure, or renal disease, comprising administering to a patient a therapeutically effective amount of the compound of claim 1 .

Assignees

• Theravance Biopharma R&D Ip Llc

Inventors

• Fleury Melissa
• Hughes Adam D

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P13/00

  Drugs for disorders of the urinary system · CPC title