Neprilysin inhibitors

Patent metadata

Field	Value
Publication number	US-10053417-B2
Application number	US-201715806722-A
Country	US
Kind code	B2
Filing date	Nov 8, 2017
Priority date	Mar 5, 2013
Publication date	Aug 21, 2018
Grant date	Aug 21, 2018

Abstract

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

where R 1 -R 5 and X 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 processes and intermediates for preparing such compounds.

First claim

What is claimed is:

1. A compound of:

where:
R 1 is selected from the group consisting of H; C 1-8 alkyl optionally substituted with one or more fluoro atoms; C 1-3 alkylene-C 6-10 aryl; C 1-3 alkylene-C 1-9 heteroaryl; C 3-7 cycloalkyl; C 2-3 alkylene-OH; —[(CH 2 ) 2 O] 1-3 CH 3 ; C 1-6 alkylene-OC(O)R 20 ; C 1-6 alkylene-NR 21 R 22 ; —CH 2 CH(NH 2 )—COOCH 3 ; C 1-6 alkylene-C(O)R 23 ; C 0-6 alkylenemorpholine; C 1-6 alkylene-SO 2 —C 1-6 alkyl;

R 2 is —CH 2 OH and R 3 is —CH 3 ;
R 4 and R 5 are independently selected from the group consisting of hydrogen, halo, —OH, —CH 3 , —OCH 3 , —CN, and —CF 3 ;
or a pharmaceutically-acceptable salt thereof.

2. (2S,4R)-5-(3′-chlorobiphenyl-4-yl)-4-formylamino-2-hydroxymethyl-2-methyl-pentanoic acid or a pharmaceutically-acceptable salt thereof.

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

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

5. 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 or 2 .

Assignees

• Theravance Biopharma R&D Ip Llc

Inventors

• Fenster Erik
• Fleury Melissa
• Hughes Adam D

Classifications

• A61P43/00

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

• A61P9/12

  Antihypertensives · CPC title

• A61P9/04

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

• A61P13/12

  of the kidneys · CPC title

• C07C235/80

  having carbon atoms of carboxamide groups and keto groups bound to the same carbon atom, e.g. acetoacetamides · CPC title