N-aryl pyrazoles, indazoles and azaindazoles as antagonists of CC chemokine receptor 1: patent cooperation treaty applications WO2010/036632, WO2009/134666 and WO2009/137338.
BACKGROUND
CC chemokine receptor 1 (CCR1) is a GPCR involved in the migration and activation of leukocytes. A number of studies have highlighted a role for CCR1 in preclinical animal models of inflammatory diseases, including MS and rheumatoid arthritis.


OBJECTIVE
This review examines three reports on a new series of CCR1 antagonists.


METHODS
The compounds of the title inventions are put in the context of earlier work in the area of CCR1 antagonism. The structure-activity relationships disclosed in the inventions are also discussed.


CONCLUSIONS
Several of the compounds disclosed in patent cooperation treaty applications WO 2010/036632, WO 2009/134666 and WO 2009/137338 are sub-nanomolar antagonists of MIP-1α-induced calcium flux in CCR1-bearing cells. Further preclinical studies are required with these new CCR1 antagonists in order to understand their potential for ameliorating human inflammatory diseases.
Carter
Percy H
PH
Bristol-Myers Squibb Company, Research & Development, Princeton, NJ 08543, USA. percy.carter@bms.com
Hynes
John
J
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007191:Indazoles / Q000737:chemistry / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D007962:Leukocytes / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000503:physiopathology; D010330:Patents as Topic; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
C515300:CCR1 protein, human; D007191:Indazoles; D011720:Pyrazoles; D054389:Receptors, CCR1; D002118:Calcium