N-aryl pyrazoles, indazoles and azaindazoles as antagonists of CC chemokine receptor 1: patent cooperation treaty applications WO2010/036632, WO2009/134666 and WO2009/137338

摘要

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.