Potent antagonists of the Kv1.5 potassium channel: synthesis and evaluation of analogous N,N-diisopropyl-2-(pyridine-3-yl)acetamides.
Kausik K Nanda, M Brad Nolt, Matthew J Cato, Stefanie A Kane, Laszlo Kiss, Robert H Spencer, Jixin Wang, Joseph J Lynch, Christopher P Regan, Gary L Stump, Bing Li, Rebecca White, Suzie Yeh, Michael J Bogusky, Mark T Bilodeau, Christopher J Dinsmore, Craig W Lindsley, George D Hartman, Scott E Wolkenberg, B Wesley Trotter
Department of Medicinal Chemistry, Merck Research Laboratories, Merck and Co., Inc., PO Box 4, West Point, PA 19486, USA.
Bioorganic & medicinal chemistry letters 2006 Nov 15This letter describes the discovery of a novel series of potent Kv1.5 ion channel antagonists based on a diisopropyl amide scaffold. Structure-activity relationships of functionalized analogs are discussed. Key compound 1-(3-(diisopropylcarbamoyl)-2-phenyl-3-(pyridin-3-yl)propyl)-3-(2-fluorobenzyl)urea (10) exhibits significant atrial-selective effects in an in vivo model.
Citation
Kausik K Nanda, M Brad Nolt, Matthew J Cato, Stefanie A Kane, Laszlo Kiss, Robert H Spencer, Jixin Wang, Joseph J Lynch, Christopher P Regan, Gary L Stump, Bing Li, Rebecca White, Suzie Yeh, Michael J Bogusky, Mark T Bilodeau, Christopher J Dinsmore, Craig W Lindsley, George D Hartman, Scott E Wolkenberg, B Wesley Trotter. Potent antagonists of the Kv1.5 potassium channel: synthesis and evaluation of analogous N,N-diisopropyl-2-(pyridine-3-yl)acetamides. Bioorganic & medicinal chemistry letters. 2006 Nov 15;16(22):5897-901
Mesh Tags
Substances
PMID: 16949818
View Full Text
