Substituted dipiperidine alcohols as potent CCR2 antagonists.
The synthesis and biological evaluation of a series of substituted dipiperidine alcohols are described. Structure-activity relationship studies led to the discovery of potent CCR2 antagonists displaying IC(50) values in the nanomolar or subnanomolar range. The cinnamoyl compounds had higher binding affinities than the corresponding urea analogs.
Xia
Mingde
M
Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 8 Clarke Drive, Cranbury, NJ 08512, USA. mxia@prdus.jnj.com
Hou
Cuifen
C
Demong
Duane
D
Pollack
Scott
S
Pan
Meng
M
Brackley
James
J
Singer
Monica
M
Matheis
Michele
M
Cavender
Druie
D
Wachter
Michael
M
D000438:Alcohols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000438:Alcohols; D010880:Piperidines; D054390:Receptors, CCR2