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

Autor: Edward J. Sullivan, Kevin Lloyd Greenman, J. J. Kim Wright, Xu Yuan, Wei Chen, Subhabrata Sen, James B. Aggen, Li Lianfa, Andrew M. K. Pennell, Derek Hansen, Penglie Zhang, Daniel J. Dairaghi, Trevor T. Charvat
Rok vydání: 2013
Předmět:
Zdroj: Bioorganic & Medicinal Chemistry Letters. 23:1228-1231
ISSN: 0960-894X
DOI: 10.1016/j.bmcl.2013.01.005
Popis: 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.
Databáze: OpenAIRE