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ID: ALA2311449

Journal: Bioorg Med Chem Lett

Title: Synthesis and evaluation of diphenylphosphinic amides and diphenylphosphine oxides as inhibitors of Kv1.5.

Authors: Olsson RI, Jacobson I, Boström J, Fex T, Björe A, Olsson C, Sundell J, Gran U, Öhrn A, Nordin A, Gyll J, Thorstensson M, Hayen A, Aplander K, Hidestål O, Jiang F, Linhardt G, Forsström E, Collins T, Sundqvist M, Lindhardt E, Åstrand A, Löfberg B.

Abstract: Diphenylphosphinic amides and diphenylphosphine oxides have been synthesized and tested as inhibitors of the Kv1.5 potassium ion channel as a possible treatment for atrial fibrillation. In vitro structure-activity relationships are discussed and several compounds with Kv1.5 IC(50) values of <0.5 μM were discovered. Selectivity over the ventricular IKs current was monitored and selective compounds were found. Results from a rabbit PD-model are included.

CiteXplore: 23260347

DOI: 10.1016/j.bmcl.2012.11.098