Neprilysin inhibitors

Patent metadata

Field	Value
Publication number	US-9771337-B2
Application number	US-201615289356-A
Country	US
Kind code	B2
Filing date	Oct 10, 2016
Priority date	May 31, 2011
Publication date	Sep 26, 2017
Grant date	Sep 26, 2017

Abstract

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

where R 1 , R 2 , R 3 , X, R 4 , R 5 , and R 6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

First claim

What is claimed is:

1. A compound of:
(a) (2R,3R)-4-(2-Chloro-phenyl)-3-{[3-(2-chloro-phenyl)-isoxazole-5-carbonyl]-amino}-2-hydroxy-butyric acid;
(b) (2R,3R)-4-(2-Chloro-phenyl)-3-{[3-(3-chloro-phenyl)-isoxazole-5-carbonyl]-amino}-2-hydroxy-butyric acid;
(c) (2R,3R)-4-(2-Chloro-phenyl)-3-{[3-(4-chloro-phenyl)-isoxazole-5-carbonyl]-amino}-2-hydroxy-butyric acid;
(d) (2R,3R)-4-(2-Chloro-phenyl)-3-{[5-(2-chloro-phenyl)-isoxazole-3-carbonyl]-amino}-2-hydroxy-butyric acid;
(e) (2R,3R)-3-{[2-(4-Chloro-2-fluoro-benzyl)-3-oxo-2,3-dihydro-isoxazole-5-carbonyl]-amino}-4-(2-chloro-phenyl)-2-hydroxy-butyric acid;
(f) (2R,3R)-4-(2-Chloro-phenyl)-3-{[2-(2,3-difluoro-4-methoxy-benzyl)-3-oxo-2,3-dihydro-isoxazole-5-carbonyl]-amino}-2-hydroxy-butyric acid;
(g) (2R,3R)-4-(2-Chloro-phenyl)-2-hydroxy-3-[(2-phenyl-oxazole-5-carbonyl)-amino]-butyric acid; or
a pharmaceutically acceptable salt thereof.

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

3. The pharmaceutical composition of claim 2 , further comprising an AT 1 receptor antagonist.

4. 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
• Gendron Roland
• Hughes Adam D
• Schmidt Jane

Classifications

• A61P9/04

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

• A61P43/00

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

• A61P9/12

  Antihypertensives · CPC title

• A61K31/437

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title

• C07D237/24

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen · CPC title