title: 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.affiliation: Chemical Sciences, Wyeth Research, Collegeville, Pennsylvania 19426, USA. blassb@wyeth.com
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Blass
authors.forename: Andrew
authors.initials: A
authors.lastname: Fensome
authors.forename: Eugene
authors.initials: E
authors.lastname: Trybulski
authors.forename: Ronald
authors.initials: R
authors.lastname: Magolda
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gardell
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.forename: Manoj
authors.initials: M
authors.lastname: Samuel
authors.forename: Irene
authors.initials: I
authors.lastname: Feingold
authors.forename: Christine
authors.initials: C
authors.lastname: Huselton
authors.forename: Chris M
authors.initials: CM
authors.lastname: Jackson
authors.forename: Laurent
authors.initials: L
authors.lastname: Djandjighian
authors.forename: Douglas
authors.initials: D
authors.lastname: Ho
authors.forename: James
authors.initials: J
authors.lastname: Hennan
authors.forename: John M
authors.initials: JM
authors.lastname: Janusz
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000188:drug therapy*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D006801:Humans; D048289:Imidazolidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D051666:Kv1.5 Potassium Channel / Q000037:antagonists & inhibitors*; D008862:Microsomes, Liver / Q000378:metabolism; D018408:Patch-Clamp Techniques; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: C545532:1-(methylsulfonylamino)-3-(2-(4-methoxyphenyl)ethyl)-4-(4-methoxyphenyl)-2-imidazolidinone; D000889:Anti-Arrhythmia Agents; D048289:Imidazolidines; C496981:KCNA5 protein, human; D051666:Kv1.5 Potassium Channel; D013449:Sulfonamides