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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.

Introduction: CC chemokine receptor 2 (CCR2) is a key mediator of the activation and migration of inflammatory monocytes. As such, it has been investigated extensively as a target for therapeutic intervention in a diverse range of diseases. Areas covered: This article reviews both the patent and peer-reviewed literature on the discovery of CCR2 antagonists from January 2009 to December 2012. Developments have occurred within each of the major chemical families of CCR2 antagonists, and are framed in that context. As has been true historically, a number of the compound families also exhibit substantial activity against the related CC chemokine receptor 5 (CCR5), making them formally CCR2/5-dual antagonists. Expert opinion: Significant progress continues to be made in identifying novel, potent CCR2 antagonists. In addition, researchers have had success in addressing issues related to selectivity, cardiac safety, and preclinical pharmacokinetics. Establishing proof-of-concept in clinical trials remains the pr...

Background: CC chemokine receptor 2 (CCR2) is a GPCR involved in the migration and activation of inflammatory monocytes. A number of studies have highlighted a role for CCR2 in preclinical animal models of atherosclerosis, restenosis, multiple sclerosis, rheumatoid arthritis and insulin resistance. Accordingly, pharmaceutical scientists have been investigating the antagonism of CCR2 as a potential therapy.Objective: This patent evaluation examines the report of a new chemical subseries of CCR2 antagonists.Methods: The compounds of the title invention are compared to the related earlier work in the area of CCR2 antagonism.Conclusions: The compounds disclosed in PCT application WO 2009023754 extend previous work in a dipiperidine series of CCR2 antagonists through the introduction of both a 1,2-disubstituted ethanol spacer and a 1′H-spiro[indene-1,4′-piperin]-1′-yl group. These compounds may represent a means of treating diseases driven by CCR2-bearing leukocytes.