Title of article :
Synthesis and SAR of 1,2-trans-(1-hydroxy-3-phenylprop-1-yl)cyclopentane carboxamide derivatives, a new class of sodium channel blockers
Author/Authors :
Dong-Ok Kim، نويسنده , , Chunshi Li، نويسنده , , Catherine Abbadie، نويسنده , , John P. Felix، نويسنده , , Michael H. Fisher، نويسنده , , Maria L. Garcia، نويسنده , , Gregory J. Kaczorowski، نويسنده , , Kathryn A. Lyons، نويسنده , , William J. Martin، نويسنده , , Birgit T. Priest، نويسنده , , McHardy M. Smith، نويسنده , , Brande S. Williams، نويسنده , , Matthew J. Wyvratt Jr.، نويسنده , , William H. Parsons، نويسنده ,
Abstract :
Novel cyclopentane-based 3-phenyl-1-hydroxypropyl compounds were evaluated for inhibitory activity against the peripheral nerve sodium channel NaV1.7 and off-target activity against the cardiac potassium channel hERG. The stereochemistry of the hydroxyl group and substitution on the phenyl rings with either fluorinated O-alkyl or alkyl groups were found to be critical for conferring potency against NaV1.7. A benchmark compound from this series displayed efficacy in rat models of inflammatory and neuropathic pain.
