2--7--dichlorodihydrofluorescein and pyrroline

Under the hypothesis that cardioprotective agents might benefit from synergism between antiarrhythmic activity and antioxidant properties, a small series of mexiletine analogues were coupled with the 2,2,5,5-tetramethylpyrroline moiety, known for its antioxidant effect, in order to obtain dual-acting drugs potentially useful in the protection of the heart against post-ischemic reperfusion injury. The pyrroline derivatives reported herein were found to be more potent as antiarrhythmic agents than mexiletine and displayed antioxidant activity. The most interesting tetramethylpyrroline congener, a tert-butyl-substituted analogue, was at least 100 times more active as an antiarrhythmic than mexiletine.

Topics: Animals; Anti-Arrhythmia Agents; Antioxidants; Density Functional Theory; Fluoresceins; Guinea Pigs; Humans; Molecular Structure; Pyrroles; Reperfusion Injury; Tumor Cells, Cultured; Voltage-Gated Sodium Channel Blockers; Voltage-Gated Sodium Channels