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ID: ALA2321873

Journal: Bioorg Med Chem Lett

Title: 1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanones as novel CCR1 antagonists.

Authors: Pennell AM, Aggen JB, Sen S, Chen W, Xu Y, Sullivan E, Li L, Greenman K, Charvat T, Hansen D, Dairaghi DJ, Wright JJ, Zhang P.

Abstract: A novel series of CCR1 antagonists based on the 1-(4-phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanone scaffold was identified by screening a compound library utilizing CCR1-expressing human THP-1 cells. SAR studies led to the discovery of the highly potent and selective CCR1 antagonist 14 (CCR1 binding IC(50)=4 nM using [(125)I]-CCL3 as the chemokine ligand). Compound 14 displayed promising pharmacokinetic and toxicological profiles in preclinical species.

CiteXplore: 23374868

DOI: 10.1016/j.bmcl.2013.01.005