Referenced in: none

Automatically associated channels: Kv1.5 , Kv11.1

Title: Discovery and synthesis of tetrahydroindolone derived semicarbazones as selective Kv1.5 blockers.

Authors: Shengde Wu, Andrew Fluxe, John M Janusz, James B Sheffer, Greg Browning, Benjamin Blass, Keith Cobum, Richard Hedges, Michael Murawsky, Bin Fang, Gina M Fadayel, Michelle Hare, Laurent Djandjighian

Journal, date & volume: Bioorg. Med. Chem. Lett., 2006 Nov 15 , 16, 5859-63

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16942874

Abstract
A novel class of tetrahydroindolone-derived semicarbazones has been discovered as potent Kv1.5 blockers. In in vitro studies, several compounds exhibited very good potency for blockade of Kv1.5. Compound 8i showed good selectivity for blockade of Kv1.5 vs hERG and L-type calcium channels. In an anesthetized pig model, compounds 8i and 10c increased atrial ERP about 28%, 18%, respectively, in the right atrium without affecting ventricular ERP.