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

…, Y Xu, E Sullivan, L Li, K Greenman, T Charvat…

Index: Pennell, Andrew M.K.; Aggen, James B.; Sen, Subhabrata; Chen, Wei; Xu, Yuan; Sullivan, Edward; Li, Lianfa; Greenman, Kevin; Charvat, Trevor; Hansen, Derek; Dairaghi, Daniel J.; Wright, J.J. Kim; Zhang, Penglie Bioorganic and Medicinal Chemistry Letters, 2013 , vol. 23, # 5 p. 1228 - 1231

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Citation Number: 6

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 IC50= 4nM using [125I]-CCL3 as the chemokine ligand). Compound 14 displayed promising pharmacokinetic and toxicological ...