Spiroindenes and spiroindanes as antagonists of CC chemokine receptor 2: WO 2009023754

Abstract

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.

Keywords::

• atherosclerosis
• autoimmune disease
• CCR2
• chemokine
• cinnamide
• GPCR
• inflammation
• spiroindene

Notes