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.
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.
Blass
Benjamin E
BE
Chemical Sciences, Wyeth Research, Collegeville, Pennsylvania 19426, USA. blassb@wyeth.com
Fensome
Andrew
A
Trybulski
Eugene
E
Magolda
Ronald
R
Gardell
Stephen J
SJ
Liu
Kun
K
Samuel
Manoj
M
Feingold
Irene
I
Huselton
Christine
C
Jackson
Chris M
CM
Djandjighian
Laurent
L
Ho
Douglas
D
Hennan
James
J
Janusz
John M
JM
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
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