Pyrazole derivatives useful as 5-lipoxygenase activating protein (FLAP) inhibitors

Patent metadata

Field	Value
Publication number	US-10183947-B2
Application number	US-201615571291-A
Country	US
Kind code	B2
Filing date	May 3, 2016
Priority date	May 4, 2015
Publication date	Jan 22, 2019
Grant date	Jan 22, 2019

Abstract

The present application relates to novel compounds of formula (I)

to their utility in treating and/or preventing clinical conditions including cardiovascular diseases (CVD), to methods for their therapeutic use, to pharmaceutical compositions containing them and to processes for preparing such compounds.

First claim

The invention claimed is:

1. A compound of formula (IV):

or a pharmaceutically acceptable salt thereof, wherein:
X 1 is CH or CCH 3 ;
R 2 is —H or —F;
R 4 is —H or —CH 3 ; and
R 8 is —H or CH 3 .

2. A compound, or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein X 1 is CH.

3. A compound, or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 2 is H.

4. A compound, or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 4 is —CH 3 .

5. A compound, or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 8 is H.

6. A compound, or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein the compound is selected from:
(1R,2R)-2-[4-(3-Methyl-1H-pyrazol-5-yl)benzoyl]-N-(4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)cyclohexanecarboxamide;
(1R,2R)-N-(5-Methyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)-2-[4-(5-methyl-1H-pyrazol-3-yl)benzoyl]cyclohexanecarboxamide;
(1R,2R)-N-(5-Methyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)-2-[4-(1H-pyrazol-3-yl)benzoyl]cyclohexanecarboxamide;
(1R,2R)-N-(4-Oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)-2-[4-(1H-pyrazol-5-yl)benzoyl]cyclohexanecarboxamide;
(1R-2R)-N-(2-Methyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)-2-[4-(5-methyl-1H-pyrazol-3-yl)benzoyl]cyclohexanecarboxamide; and
(1R,2R)-N-(2-Methyl-4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)-2-[4-1H-pyrazol-5-yl)benzoyl]cyclohexanecarboxamide.

7. A compound according to claim 1 , which is (1R,2R)-2-[4-(3-Methyl-1H-pyrazol-5-yl)benzoyl]-N-(4-oxo-4,5,6,7-tetrahydropyraczolo[1,5-a]pyrazin-3-yl)cyclohexanecarboxamide; or a pharmaceutically acceptable salt thereof.

8. A compound according to claim 1 , which is (1R,2R)-2-[4-(3-Methyl-1H-pyrazol-5-yl)benzoyl]-N-(4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)cyclohexanecarboxamide.

9. A pharmaceutical composition comprising a compound according to any of claims 1 or 2 - 8 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier, diluent, or excipient.

Assignees

• Astrazeneca Ab

Inventors

• Broddefalk Johan Olof
• Emtenäs Hans Fredrik
• Granberg Kenneth Lars
• Lemurell Malin Anita
• Pettersen Daniel Tor
• Plowright Alleyn Thomas
• Ulander Lars Johan Andreas

Classifications

• 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

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title