Discovery of a brain-sparing GIRK1/4 inhibitor for pharmacological cardioversion of atrial fibrillation.
Bioorganic & medicinal chemistry letters(2023)
摘要
Atrial fibrillation (AF) is the most common cardiac arrhythmia, and a significant risk factor for ischemic stroke and heart failure. Marketed anti-arrhythmic drugs can restore sinus rhythm, but with limited efficacy and significant toxicities, including potential to induce ventricular arrhythmia. Atrial-selective ion channel drugs are expected to restore and maintain sinus rhythm without risk of ventricular arrhythmia. One such atrial-selective channel target is GIRK1/4 (G-protein regulated inwardly rectifying potassium channel 1/4). Here we describe 14b, a potent GIRK1/4 inhibitor developed to cardiovert AF to sinus rhythm while minimizing central nervous system exposure - an issue with preceding GIRK1/4 clinical candidates.
更多查看译文
关键词
Atrial fibrillation,Cardioversion,GIRK1/4 inhibitor,Peripherally restricted drug
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要