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

Abstract

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.

Keywords::

• CCR1
• chemokine
• GPCR
• indazoles
• inflammation
• MS
• pyrazoles
• rheumatoid arthritis

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