Selective Kv1.5 blockers: development of (R)-1-(methylsulfonylamino)-3-[2-(4-methoxyphenyl)ethyl]-4-(4-methoxyphenyl)-2-imidazolidinone (KVI-020/WYE-160020) as a potential treatment for atrial arrhythmia.

Abstract

Atrial fibrillation is the most prevalent form of cardiac arrhythmia. Current treatments extend the atrial effective refractory period by nonselective blockade of cardiac ion channels. An alternative approach selectively targeting the Kv1.5 ion channel offers the opportunity for therapeutic benefit with decreased risk of adverse cardiovascular events. KVI-020 (4g) successfully demonstrated antiarrhythmic efficacy in a canine arrhythmia model, and these findings support its utility as an antiarrhythmic agent.

• Authors: Benjamin E Blass, Andrew Fensome, Eugene Trybulski, Ronald Magolda, Stephen J Gardell, Kun Liu, Manoj Samuel, Irene Feingold, Christine Huselton, Chris M Jackson, Laurent Djandjighian, Douglas Ho, James Hennan, John M Janusz
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 52 Issue 21 Pg. 6531-4 (Nov 12 2009) ISSN: 1520-4804 [Electronic] United States
• PMID: 19888755 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-(methylsulfonylamino)-3-(2-(4-methoxyphenyl)ethyl)-4-(4-methoxyphenyl)-2-imidazolidinone
• Anti-Arrhythmia Agents
• Imidazolidines
• KCNA5 protein, human
• Kv1.5 Potassium Channel
• Sulfonamides

Topics

• Animals
• Anti-Arrhythmia Agents (chemical synthesis, pharmacokinetics, pharmacology)
• Atrial Fibrillation (drug therapy)
• Cell Line
• Cricetinae
• Cricetulus
• Dogs
• Humans
• Imidazolidines (chemical synthesis, pharmacokinetics, pharmacology)
• In Vitro Techniques
• Kv1.5 Potassium Channel (antagonists & inhibitors)
• Microsomes, Liver (metabolism)
• Patch-Clamp Techniques
• Solubility
• Stereoisomerism
• Structure-Activity Relationship
• Sulfonamides (chemical synthesis, pharmacokinetics, pharmacology)