Design and synthesis of novel isoquinoline-3-nitriles as orally bioavailable Kv1.5 antagonists for the treatment of atrial fibrillation |
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| Authors: | 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 |
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| Affiliation: | Department of Medicinal Chemistry, Merck Research Laboratories, WP14-2, P.O. Box 4, Sumneytown Pike, West Point, Pennsylvania 19486, USA. bwesley_trotter@merck.com |
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| Abstract: | 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, IKur. Structural modifications of isoquinolinone lead 1 afforded compounds with excellent potency, selectivity, and oral bioavailability. |
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