Compounds

Patent metadata

Field	Value
Publication number	US-9783546-B2
Application number	US-201515327685-A
Country	US
Kind code	B2
Filing date	Jul 21, 2015
Priority date	Jul 22, 2014
Publication date	Oct 10, 2017
Grant date	Oct 10, 2017

Abstract

The present invention relates to novel compounds that inhibit Lp-PLA 2 activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases associated with the activity of Lp-PLA 2 , for example atherosclerosis, Alzheimer's disease.

First claim

What is claimed is:

1. A compound which is

or a salt thereof.

2. A compound which is

or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 which is (R)-3-((3, 5-difluoro-4-((2-(trifluoromethyl) pyridin-4-yl) oxy) benzyl) oxy)-7, 8, 8a, 9-tetra hydropyrrolo[1′,2′:3 ,4]imidazo [1,2-c]pyrimidin-1(6H)-one

or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 which is (R)-3-((3, 5-difluoro-4-((2-(trifluoromethyl) pyridin-4-yl) oxy) benzyl) oxy)-7, 8, 8a, 9-tetra hydropyrrolo[1′,2′:3,4]imidazo[1,2-c]pyrimidin-1(6H)-one

5. The compound according to claim 1 which is a pharmaceutically acceptable salt of (R)-3-((3, 5-difluoro-4-((2-(trifluoromethyl) pyridin-4-yl) oxy) benzyl) oxy)-7, 8, 8a, 9-tetra hydropyrrolo[1′,2′:3,4]imidazo[1,2-c]pynmidin-1(6H)-one

6. The compound according to claim 1 which is (S)-3-((3, 5-difluoro-4-((2-(trifluoromethyl) pyridin-4-yl) oxy) benzyl) oxy)-7, 8, 8a, 9-tetra hydropyrrolo[1′,2′:3 ,4]imidazo[1,2-c]pyrimidin-1(6H)-one

or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 1 , which is (S)-3-((3, 5-difluoro-4-((2-(trifluoromethyl) pyridm-4-yl) oxy) benzyl) oxy)-7, 8, 8a, 9-tetra hydropyrrolo[1′,2′:3 ,4]imidazo[1,2-c]pyrimidin-1(6H)-one

8. The compound according to claim 1 , which is a pharmaceutically acceptable salt of (S)-3-((3, 5-difluoro-4-((2-(trifluoromethyl) pyridm-4-yl) oxy) benzyl) oxy)-7, 8, 8a, 9-tetra hydropyrrolo[1′,2′:3,4]imidazo[1,2-c]pyrimidin-1(6H)-one

9. A pharmaceutical composition comprising a compound having a structure of

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

10. The pharmaceutical composition according to claim 9 wherein the compound has the structure of

or a pharmaceutically acceptable salt thereof.

11. The pharmaceutical composition according to claim 9 wherein the compound has the structure of

or a pharmaceutically acceptable salt thereof.

12. A method for treating neurodegeneration disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound having a structure of

or a pharmaceutically acceptable salt thereof.

13. The method according to claim 12 , wherein the neurodegeneration disease is Alzheimer's disease.

14. The method according to claim 12 , wherein the compound has the structure of

or a pharmaceutically acceptable salt thereof.

15. The method according to claim 12 , wherein the compound has the structure of

or a pharmaceutically acceptable salt thereof.

16. The method according to claim 12 , wherein the subject is human.

Assignees

• Glaxosmithkline Ip Dev Ltd

Inventors

• Wan Zehong
• Zhang Xiaomin
• Wang Jian

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P35/00

  Antineoplastic agents · 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

• A61P5/18

  of the parathyroid hormones · CPC title

• A61P43/00

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