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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
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2013 Mar 01; Vol. 23 (5), pp. 1228-31. Date of Electronic Publication: 2013 Jan 11.
Publication Year :
2013

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.<br /> (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
23
Issue :
5
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
23374868
Full Text :
https://doi.org/10.1016/j.bmcl.2013.01.005