title: 1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanones as novel CCR1 antagonists.
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.
authors: ChemoCentryx, Inc., 850 Maude Avenue, Mountain View, CA 94043, USA.
authors: Andrew M K
authors: AM
authors: Pennell
authors: James B
authors: JB
authors: Aggen
authors: Subhabrata
authors: S
authors: Sen
authors: Wei
authors: W
authors: Chen
authors: Yuan
authors: Y
authors: Xu
authors: Edward
authors: E
authors: Sullivan
authors: Lianfa
authors: L
authors: Li
authors: Kevin
authors: K
authors: Greenman
authors: Trevor
authors: T
authors: Charvat
authors: Derek
authors: D
authors: Hansen
authors: Daniel J
authors: DJ
authors: Dairaghi
authors: J J Kim
authors: JJ
authors: Wright
authors: Penglie
authors: P
authors: Zhang
mesh_terms: D002460:Cell Line; D006801:Humans; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C515300:CCR1 protein, human; D010879:Piperazines; D011720:Pyrazoles; D054389:Receptors, CCR1