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

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, R1 = OH, R2 = NH2), a compound currently under clinical evaluation. Selected compounds with the desired in-vitro profile demonstrated positive in vivo results in the mouse CaCl2 arrhythmia model upon oral administration.

Graphical abstractEfficacious gap-junction modifiers that re-establish intercellular communications and delay time to cardiac conduction block in mice treated with intravenous CaCl2 are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide