Referenced in: none

Automatically associated channels: Kv11.1

Title: Synthesis and biological evaluation of pyrrolidine derivatives as novel and potent sodium channel blockers for the treatment of ischemic stroke.

Authors: Maki Seki, Osamu Tsuruta, Ryo Tatsumi, Aki Soejima

Journal, date & volume: Bioorg. Med. Chem. Lett., 2013 Jul 15 , 23, 4230-4

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23743284

Abstract
A novel series of pyrrolidine derivatives as Na(+) channel blockers was synthesized and evaluated for their inhibitory effects on neuronal Na(+) channels. Structure-activity relationship (SAR) studies of a pyrrolidine analogue 2 led to the discovery of 5e as a potent Na(+) channel blocker with a low inhibitory action against human ether-a-go-go-related gene (hERG) channels. Compound 5e showed remarkably neuroprotective activity in a rat transient middle cerebral artery occlusion (MCAO) model, suggesting that 5e would act as a neuroprotectant for ischemic stroke.