Organic compounds

Patent metadata

Field	Value
Publication number	US-9546175-B2
Application number	US-201514820248-A
Country	US
Kind code	B2
Filing date	Aug 6, 2015
Priority date	Aug 7, 2014
Publication date	Jan 17, 2017
Grant date	Jan 17, 2017

Abstract

The invention relates to novel inhibitors of phosphodiesterase 1 (PDE1), useful for the treatment of diseases or disorders characterized by disruption of or damage to certain cGMP/PKG mediated pathways (e.g., in cardiac tissue). The invention further relates to pharmaceutical composition comprising the same and methods of treatment of cardiovascular disease and related disorders, e.g., congestive heart disease, atherosclerosis, myocardial infarction, and stroke.

First claim

What is claimed is:

1. A compound of Formula I:

in free or salt form, wherein
(i) R 1 is —NH(R 4 ), wherein R 4 is phenyl optionally substituted with halo;
(ii) R 2 is H or C 1-6 alkyl;
(iii) R 3 is —SO 2 NH 2 or —COOH.

2. The compound according to claim 1 , wherein R 1 is —NH(R 4 ), and wherein R 4 is phenyl.

3. The compound according to claim 1 , wherein R 1 is —NH(R 4 ), and wherein R 4 is 4-fluorophenyl.

4. The compound according to claim 1 , wherein R 2 is C 1-6 alkyl.

5. The compound according to claim 1 , wherein R 2 is isobutyl.

6. The compound according to claim 1 , wherein R 2 is neopentyl.

7. The compound according to claim 1 , wherein R 3 is SO 2 NH 2 .

8. The compound according to claim 1 , wherein R 3 is —COOH.

9. The compound according to claim 1 which is the compound:

in free or salt form.

10. The compound according to claim 1 which is the compound:

in free or salt form.

11. The compound according to claim 1 which is the compound:

in free or salt form.

12. A combination comprising a compound according to claim 1 , in free or pharmaceutically acceptable salt form, and one or more other therapeutic agents useful for the treatment of cardiovascular disorders, in free or pharmaceutically acceptable salt form.

13. A pharmaceutical composition comprising a compound according to claim 1 , in free or pharmaceutically acceptable salt form, in admixture with a pharmaceutically acceptable diluent or carrier.

14. A method for the treatment of a disease or disorder which may be ameliorated by modulating cGMP/PKG-dependent signaling pathways comprising administering to a patient in need thereof an effective amount of the compound according to claim 1 , in free or pharmaceutically acceptable salt form; wherein the disease or disorder is congestive heart failure.

15. The method according to claim 14 , further comprising administering a PDE5 inhibitor, in free or pharmaceutically acceptable salt form.

16. A pharmaceutical composition comprising the combination according to claim 12 , in admixture with a pharmaceutically acceptable diluent or carrier.

Assignees

• Intra Cellular Therapies Inc

Inventors

• Li Peng
• Zheng Hailin
• Zhao Jun
• Wennogle Lawrence P

Classifications

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61K31/00

  Medicinal preparations containing organic active ingredients · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title