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  • Title: N-aryl pyrazoles, indazoles and azaindazoles as antagonists of CC chemokine receptor 1: patent cooperation treaty applications WO2010/036632, WO2009/134666 and WO2009/137338.
    Author: Carter PH, Hynes J.
    Journal: Expert Opin Ther Pat; 2010 Nov; 20(11):1609-18. PubMed ID: 20858032.
    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.
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