Neprilysin inhibitors

Patent metadata

Field	Value
Publication number	US-10759813-B2
Application number	US-201916410361-A
Country	US
Kind code	B2
Filing date	May 13, 2019
Priority date	Dec 15, 2010
Publication date	Sep 1, 2020
Grant date	Sep 1, 2020

Abstract

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

where R 1 -R 6 , a, b, 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. (2R,4R)-5-Biphenyl-4-yl-4-{[5-(3-carbamoylpyrrolidine-1-carbonyl)-2H-pyrazole-3-carbonyl]-amino}-2-hydroxy-pentanoic acid or a pharmaceutically acceptable salt thereof.

2. (2R,4R)-5-Biphenyl-4-yl-2-hydroxy-4-{[5-(4-hydroxypiperidine-1-carbonyl)-2H-pyrazole-3-carbonyl]-amino}-pentanoic acid or a pharmaceutically acceptable salt thereof.

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

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

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

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

7. The pharmaceutical composition of claim 5 , wherein the AT 1 receptor antagonist is selected from abitesartan, azilsartan, azilsartan medoxomil, benzyllosartan, candesartan, candesartan cilexetil, elisartan, embusartan, enoltasosartan, eprosartan, EXP3174, fonsartan, forasartan, glycyllosartan, irbesartan, isoteoline, losartan, milfasartan, olmesartan, olmesartan medoxomil, opomisartan, pratosartan, ripisartan, saprisartan, saralasin, sarmesin, TAK-591, tasosartan, telmisartan, valsartan, and zolasartan.

8. The pharmaceutical composition of claim 6 , wherein the AT 1 receptor antagonist is selected from abitesartan, azilsartan, azilsartan medoxomil, benzyllosartan, candesartan, candesartan cilexetil, elisartan, embusartan, enoltasosartan, eprosartan, EXP3174, fonsartan, forasartan, glycyllosartan, irbesartan, isoteoline, losartan, milfasartan, olmesartan, olmesartan medoxomil, opomisartan, pratosartan, ripisartan, saprisartan, saralasin, sarmesin, TAK-591, tasosartan, telmisartan, valsartan, and zolasartan.

9. A method of treating hypertension, heart failure, or renal disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 1 .

10. A method of treating hypertension, heart failure, or renal disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of claim 2 .

11. A method of treating hypertension, heart failure, or renal disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 3 .

12. A method of treating hypertension, heart failure, or renal disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 4 .

13. A method of treating hypertension, heart failure, or renal disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 5 .

14. A method of treating hypertension, heart failure, or renal disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 6 .

15. A method of treating hypertension, heart failure, or renal disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 7 .

16. A method of treating hypertension, heart failure, or renal disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 8 .

17. A method of treating hypertension, heart failure, or renal disease in a subject in need thereof, comprising administering to the subject an AT 1 receptor antagonist and a therapeutically effective amount of the compound of claim 1 .

18. A method of treating hypertension, heart failure, or renal disease in a subject in need thereof, comprising administering to the subject an AT 1 receptor antagonist and a therapeutically effective amount of the compound of claim 2 .

Assignees

• Theravance Biopharma R&D Ip Llc

Inventors

• Gendron Roland
• Hughes Adam D

Classifications

• C07D231/12 Primary

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• A61K31/415

  1,2-Diazoles · CPC title

• C07D237/04

  having less than three double bonds between ring members or between ring members and non-ring members · CPC title

• A61K31/341

  not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title