Human plasma kallikrein inhibitors

Patent metadata

Field	Value
Publication number	US-10329260-B2
Application number	US-201815977129-A
Country	US
Kind code	B2
Filing date	May 11, 2018
Priority date	Mar 7, 2014
Publication date	Jun 25, 2019
Grant date	Jun 25, 2019

Abstract

Disclosed are compounds of formula I

as described herein, and pharmaceutically acceptable salts thereof. The compounds are inhibitors of plasma kallikrein. Also disclosed are pharmaceutical compositions comprising at least one such compound, and methods involving use of the compounds and compositions in the treatment and prevention of diseases and conditions characterized by unwanted plasma kallikrein activity.

First claim

What is claimed is:

1. A compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

2. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

8. A compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

9. The compound of claim 8 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

10. The compound of claim 8 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

11. The compound of claim 8 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

12. The compound of claim 8 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

13. The compound of claim 8 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

14. The compound of claim 8 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

15. A compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

16. The compound of claim 15 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

17. The compound of claim 15 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

18. The compound of claim 15 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

19. The compound of claim 15 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

20. The compound of claim 15 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

21. The compound of claim 15 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

22. A compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

23. The compound of claim 22 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

24. The compound of claim 22 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

25. The compound of claim 22 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

26. The compound of claim 22 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

27. The compound of claim 22 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

28. The compound of claim 22 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

29. The compound of claim 1 , wherein the pharmaceutically acceptable salt thereof is a hydrochloride salt.

30. The compound of claim 1 , wherein the compound is:
(+)-1-(3-(aminomethyl)phenyl)-N-(5-(((cyclopropylmethyl)amino)(phenyl)methyl)-2-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide;
(−)-1-(3-(aminomethyl)phenyl)-N-(5-(((cyclopropylmethyl)amino)(phenyl)methyl)-2-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide;
(+)-1-(3-(aminomethyl)phenyl)-N-(5-((3-cyanophenyl)(cyclopropylmethylamino)methyl)-2-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide;
(−)-1-(3-(aminomethyl)phenyl)-N-(5-((3-cyanophenyl)(cyclopropylmethylamino)methyl)-2-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide;
(+)-1-(3-(aminomethyl)phenyl)-N-(5-((cyclopropylmethylamino)(2-hydroxyphenyl)methyl)-2-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide;
(−)-1-(3-(aminomethyl)phenyl)-N-(5-((cyclopropylmethylamino)(2-hydroxyphenyl)methyl)-2-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide;
(+)-1-(3-(aminomethyl)p

Assignees

• Biocryst Pharm Inc

Inventors

• Kotian Pravin L
• Babu Yarlagadda S
• Wu Minwan
• Chintareddy Venkat R
• Kumar V Satish
• Zhang Weihe

Classifications

• A61P43/00

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

• A61P9/12

  Antihypertensives · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/10

  Antioedematous agents; Diuretics · CPC title