Discovery and in vitro/in vivo studies of tetrazole derivatives as Kv1.5 blockers

Shengde Wu; Andrew Fluxe; Jim Sheffer; John M Janusz; Benjamin E Blass; Ron White; Chris Jackson; Richard Hedges; Michael Murawsky; Bin Fang; Gina M Fadayel; Michelle Hare; Laurent Djandjighian

doi:10.1016/j.bmcl.2006.09.021

Discovery and in vitro/in vivo studies of tetrazole derivatives as Kv1.5 blockers

Bioorg Med Chem Lett. 2006 Dec 15;16(24):6213-8. doi: 10.1016/j.bmcl.2006.09.021. Epub 2006 Sep 28.

Authors

Shengde Wu¹, Andrew Fluxe, Jim Sheffer, John M Janusz, Benjamin E Blass, Ron White, Chris Jackson, Richard Hedges, Michael Murawsky, Bin Fang, Gina M Fadayel, Michelle Hare, Laurent Djandjighian

Affiliation

¹ Procter & Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Road, Mason, OH 45040, USA. wu.s.3@pg.com

PMID: 17010606
DOI: 10.1016/j.bmcl.2006.09.021

Abstract

A novel class of tetrazole-derived Kv1.5 blockers is disclosed. In in vitro studies, several compounds had IC(50)s ranging from 180 to 550 nM. In vivo studies indicated that compounds 2f and 2j increased right atrial ERP about 40% without affecting ventricular ERP.

MeSH terms

Animals
Heart Rate / drug effects
Kinetics
Kv1.5 Potassium Channel / antagonists & inhibitors*
Models, Molecular
Structure-Activity Relationship
Swine
Swine, Miniature
Tetrazoles / chemistry
Tetrazoles / pharmacology*
Thiazoles / chemistry
Thiazoles / pharmacology*

Substances

Kv1.5 Potassium Channel
Tetrazoles
Thiazoles