Discovery of triarylethanolamine inhibitors of the Kv1.5 potassium channel

Douglas C Beshore; Nigel J Liverton; Charles J McIntyre; Christopher F Claiborne; Brian Libby; J Christopher Culberson; Joseph J Salata; Christopher P Regan; Joseph J Lynch; Laszlo Kiss; Robert H Spencer; Stephanie A Kane; Rebecca B White; Suzie Yeh; George D Hartman; Christopher J Dinsmore

doi:10.1016/j.bmcl.2010.03.005

Discovery of triarylethanolamine inhibitors of the Kv1.5 potassium channel

Bioorg Med Chem Lett. 2010 Apr 15;20(8):2493-6. doi: 10.1016/j.bmcl.2010.03.005. Epub 2010 Mar 4.

Authors

Douglas C Beshore¹, Nigel J Liverton, Charles J McIntyre, Christopher F Claiborne, Brian Libby, J Christopher Culberson, Joseph J Salata, Christopher P Regan, Joseph J Lynch, Laszlo Kiss, Robert H Spencer, Stephanie A Kane, Rebecca B White, Suzie Yeh, George D Hartman, Christopher J Dinsmore

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA. douglas_beshore@merck.com

PMID: 20304642
DOI: 10.1016/j.bmcl.2010.03.005

Abstract

A series of triarylethanolamine inhibitors of the Kv1.5 potassium channel have been prepared and evaluated for their effects in vitro and in vivo. The structure-activity relationship (SAR) studies described herein led to the development of potent, selective and orally active inhibitors of Kv1.5.

MeSH terms

Animals
Dose-Response Relationship, Drug
Drug Discovery
Drug Evaluation, Preclinical
Ethanolamines / chemistry
Ethanolamines / pharmacology*
Humans
Potassium Channel Blockers / chemistry
Potassium Channel Blockers / pharmacology*
Potassium Channels, Voltage-Gated / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Ethanolamines
KCNF1 protein, human
Potassium Channel Blockers
Potassium Channels, Voltage-Gated