title: Design and synthesis of novel CCR2 antagonists: investigation of non-aryl/heteroaryl binding motifs.
abstract: This report describes the design and synthesis of a series of CCR2 antagonists incorporating novel non-aryl/heteroaryl RHS (right hand side) motifs. Previous SAR in the area has suggested an aryl/heteroaryl substituent as a necessary structural feature for binding to the CCR2 receptor. Herein we describe the SAR with regards to potency (binding to hCCR2), dofetilide activity and metabolic stability (in vitro HLM) for this series. The resulting outcome was the identification of compounds with excellent properties for the investigation of the role of CCR2 in disease.
authors.affiliation: Department of Medicinal Chemistry, Pfizer Global Research and Development, Chesterfield, MO 63017, USA. john.i.trujillo@pfizer.com
authors.forename: John I
authors.initials: JI
authors.lastname: Trujillo
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Robert O
authors.initials: RO
authors.lastname: Hughes
authors.forename: D Joseph
authors.initials: DJ
authors.lastname: Rogier
authors.forename: Steven R
authors.initials: SR
authors.lastname: Turner
authors.forename: Rajesh
authors.initials: R
authors.lastname: Devraj
authors.forename: Philip A
authors.initials: PA
authors.lastname: Morton
authors.forename: Chu-Biao
authors.initials: CB
authors.lastname: Xue
authors.forename: Ganfeng
authors.initials: G
authors.lastname: Chao
authors.forename: Maryanne B
authors.initials: MB
authors.lastname: Covington
authors.forename: Robert C
authors.initials: RC
authors.lastname: Newton
authors.forename: Brian
authors.initials: B
authors.lastname: Metcalf
mesh_terms: D001665:Binding Sites; D015195:Drug Design; D008958:Models, Molecular; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D054390:Receptors, CCR2