Design and synthesis of novel isoquinoline-3-nitriles as orally bioavailable Kv1. 5 antagonists for the treatment of atrial fibrillation

…, GL Stump, L Kiss, J Wang, RH Spencer…

文献索引：Trotter, B. Wesley; Nanda, Kausik K.; Kett, Nathan R.; Regan, Christopher P.; Lynch, Joseph J.; Stump, Gary L.; Kiss, Laszlo; Wang, Jixin; Spencer, Robert H.; Kane, Stefanie A.; White, Rebecca B.; Zhang, Rena; Anderson, Kenneth D.; Liverton, Nigel J.; McIntyre, Charles J.; Beshore, Douglas C.; Hartman, George D.; Dinsmore, Christopher J. Journal of Medicinal Chemistry, 2006 , vol. 49, # 24 p. 6954 - 6957

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被引用次数: 79

摘要

Novel 3-cyanoisoquinoline Kv1. 5 antagonists have been prepared and evaluated in in vitro and in vivo assays for inhibition of the Kv1. 5 potassium channel and its associated cardiac potassium current, I Kur. Structural modifications of isoquinolinone lead 1 afforded compounds with excellent potency, selectivity, and oral bioavailability.