Discovery of a class of potent gap-junction modifiers as novel antiarrhythmic agents

Abstract In an effort to discover potent, orally bioavailable compounds for the treatment of atrial fibrillation (AF) and ventricular tachycardia (VT), we developed a class of gap-junction modifiers typified by GAP-134 ( 1 , R 1  = OH, R 2  = NH 2 ), a compound currently under clinical evaluation. Selected compounds with the desired in-vitro profile demonstrated positive in vivo results in the mouse CaCl 2 arrhythmia model upon oral administration.