Neprilysin inhibitors

Patent metadata

Field	Value
Publication number	US-9783507-B2
Application number	US-201715419217-A
Country	US
Kind code	B2
Filing date	Jan 30, 2017
Priority date	Jan 30, 2014
Publication date	Oct 10, 2017
Grant date	Oct 10, 2017

Abstract

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

where R 1 -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 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 Formula 1:

where:
R 1 is H, —C 1-8 alkyl, —CH(CH 3 )OC(O)—O-cyclohexyl, —(CH 2 ) 2 -morpholinyl, or —CH 2 - 5-methyl-[1,3]dioxol-2-one;
R 2 is —C 0-3 alkylene-NR 22 R 23 ; R 22 is H or —C 1-6 alkyl; R 23 is H, —C 1-6 alkyl, —C 1-6 alkyl substituted with 1 to 6 fluoro atoms, —SO 2 —C 1-6 alkyl, —CH 2 OC(O)—C 1-6 alkyl, —C 2-4 alkylene-OH, —C 2-4 alkylene-O—CH 3 , or cyclopropyl optionally substituted with one or two R 31 groups; or R 22 and R 23 are taken together to form —(CH 2 ) 2 —O—(CH 2 ) 2 —, a 2-oxa-6-aza-spiro[3.3]heptane ring, or an azetidine ring optionally substituted with one or two R 31 groups; and each R 31 is independently halo, —C 1-6 alkyl, —C 0-2 alkylene-OH, —C 0-2 alkylene-OC 1-6 alkyl, —CN, or —CONH 2 ;
R 3 , R 4 and R 5 are independently H or halo; and
P 1 is H or an amino-protecting group selected from the group consisting of t-butoxycarbonyl, trityl, benzyloxycarbonyl, 9-fluorenylmethoxycarbonyl, formyl, trimethylsilyl, and t-butyldimethylsilyl; or a salt thereof.

Assignees

• Theravance Biopharma R&D Ip Llc

Inventors

• Fleury Melissa
• Beausoliel Anne-Marie
• Hughes Adam D
• Long Daniel D
• Wilton Donna A A

Classifications

• C07D231/14

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title

• C07D263/38

  attached in position 2 · CPC title

• C07D213/81

  Amides; Imides · CPC title

• C07D231/20

  One oxygen atom attached in position 3 or 5 · CPC title

• C07D249/04 Primary

  1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles · CPC title