Referenced in: none

Automatically associated channels: Kv11.1

Title: Synthesis and SAR of 1,2-trans-(1-hydroxy-3-phenylprop-1-yl)cyclopentane carboxamide derivatives, a new class of sodium channel blockers.

Authors: Dong Ok, Chunshi Li, Catherine Abbadie, John P Felix, Michael H Fisher, Maria L Garcia, Gregory J Kaczorowski, Kathryn A Lyons, William J Martin, Birgit T Priest, McHardy M Smith, Brande S Williams, Matthew J Wyvratt, William H Parsons

Journal, date & volume: Bioorg. Med. Chem. Lett., 2006 Mar 1 , 16, 1358-61

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16337121

Abstract
Novel cyclopentane-based 3-phenyl-1-hydroxypropyl compounds were evaluated for inhibitory activity against the peripheral nerve sodium channel Na(V)1.7 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 Na(V)1.7. A benchmark compound from this series displayed efficacy in rat models of inflammatory and neuropathic pain.