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: |
CCR1
Chemistry Stereochemistry Organic Chemistry Clinical Biochemistry Receptors CCR1 Antagonist Pharmaceutical Science Ligand (biochemistry) Biochemistry Piperazines Cell Line Structure-Activity Relationship Drug Discovery Humans Pyrazoles Molecular Medicine Structure–activity relationship Molecular Biology |
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 |
Externí odkaz: |