Author/Authors :
Robert J. Cherney، نويسنده , , David J. Nelson، نويسنده , , Yvonne C. Lo، نويسنده , , Gengjie Yang، نويسنده , , Peggy A. Scherle، نويسنده , , Heather Jezak، نويسنده , , Kimberly A. Solomon، نويسنده , , Percy H. Carter، نويسنده , , Carl P. Decicco، نويسنده ,
Abstract :
A series of cis-3,4-disubstituted piperidines was synthesized and evaluated as CC chemokine receptor 2 (CCR2) antagonists. Compound 24 emerged with an attractive profile, possessing excellent binding (CCR2 IC50 = 3.4 nM) and functional antagonism (calcium flux IC50 = 2.0 nM and chemotaxis IC50 = 5.4 nM). Studies to explore the binding of these piperidine analogs utilized a key CCR2 receptor mutant (E291A) with compound 14 and revealed a significant reliance on Glu291 for binding.
Keywords :
GPCR , CCR2 antagonist , CCR2 , chemokine
