Synthesis and structure-activity relationship of 7-azaindole piperidine derivatives as CCR2 antagonists.
The synthesis and structure-activity relationship of a series of 7-azaindole piperidine derivatives are described. SAR studies led to the discovery of the potent CCR2 antagonists displaying IC(50) values in the nanomolar range. The representative compound 15 showed reasonable P450 and pharmacokinetics profile.
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
Singer
Monica
M
Matheis
Michele
M
Murray
William
W
Cavender
Druie
D
Wachter
Michael
M
D000438:Alcohols / Q000737:chemistry; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018932:Chemokine CCL2 / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry*; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000438:Alcohols; C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D007211:Indoles; D010880:Piperidines; D054390:Receptors, CCR2; C032727:piperidine