Respiratory & Inflammation iMed, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden.
Bioorg Med Chem Lett. 2013 Feb 1;23(3):706-10. doi: 10.1016/j.bmcl.2012.11.098. Epub 2012 Dec 3.
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.
二苯膦酰胺和二苯膦氧化物已被合成并测试为 Kv1.5 钾离子通道的抑制剂，作为治疗心房颤动的一种可能方法。讨论了体外结构-活性关系，并发现了几种 Kv1.5 IC（50）值<0.5 μM 的化合物。监测了对心室 IKs 电流的选择性，并发现了选择性化合物。包括来自兔 PD 模型的结果。
