title: Synthesis and biological evaluation of phenyl piperidine derivatives as CCR2 antagonists.
abstract: A series of phenyl piperidine derivatives possessing potent and selective CCR2 antagonist activity is reported. Structure-activity relationship (SAR) studies have established that incorporation of a second ring system adjacent to the aryl piperidine plays an important role in determining the CCR2 potency. Both a second piperidine ring and a 1,3-substituted cyclopentylamine have been probed as linkers. For the cyclopentylamine series, the 1S,3R-configuration exhibits much higher affinity for hCCR2 than the 1R,3S-configuration. Compound 3g shows good selectivity over CCR1, CCR3, 5-HT and has an excellent P450 profile.
authors.affiliation: Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, LLC, 8 Clarke Drive, Cranbury, NJ 08512, USA. mxia@prdus.jnj.com
authors.forename: Mingde
authors.initials: M
authors.lastname: Xia
authors.forename: Cuifen
authors.initials: C
authors.lastname: Hou
authors.forename: Scott
authors.initials: S
authors.lastname: Pollack
authors.forename: James
authors.initials: J
authors.lastname: Brackley
authors.forename: Duane
authors.initials: D
authors.lastname: DeMong
authors.forename: Meng
authors.initials: M
authors.lastname: Pan
authors.forename: Monica
authors.initials: M
authors.lastname: Singer
authors.forename: Michele
authors.initials: M
authors.lastname: Matheis
authors.forename: Gil
authors.initials: G
authors.lastname: Olini
authors.forename: Druie
authors.initials: D
authors.lastname: Cavender
authors.forename: Michael
authors.initials: M
authors.lastname: Wachter
mesh_terms: D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D010880:Piperidines; D054390:Receptors, CCR2