Synthesis and biological evaluation of phenyl piperidine derivatives as CCR2 antagonists.
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.
Xia
Mingde
M
Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, LLC, 8 Clarke Drive, Cranbury, NJ 08512, USA. mxia@prdus.jnj.com
Hou
Cuifen
C
Pollack
Scott
S
Brackley
James
J
DeMong
Duane
D
Pan
Meng
M
Singer
Monica
M
Matheis
Michele
M
Olini
Gil
G
Cavender
Druie
D
Wachter
Michael
M
D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D010880:Piperidines; D054390:Receptors, CCR2