Synthesis and biological evaluation of new cyclopenteno[b]thiophene derivatives as local anesthetic and antiarrhythmic agents.

Abstract

A series of ethyl 2-substituted amino-cyclopenteno[b]thiophen-3-carboxylates was synthesized as a carticaine analogues and evaluated for their local anesthetic and antiarrhythmic activity. Compounds ethyl 2-[1-oxo-2-(ethylamino)ethylamino]-(4a), ethyl 2-[1-oxo-2-(n-propylamino)-ethylamino]-(4c), ethyl 2-[1-oxo-2-(4-methylpiperazino)ethylamino]-(4e), ethyl 2-[1-oxo-2-(ethylamino)propylamino]-(5a) and ethyl 2-[1-oxo-2-(n-propylamino)propylamino]cyclopenteno[b]thiophen++ +-3-carboxylate (5c) proved to possess local anesthetic and antiarrhythmic activity comparable to carticaine and lidocaine. The active compounds exert their antiarrhythmic potency via blocking Na+ channels as in case of 5c or blocking Ca+2 channels as in case of 4a, 4c and 5c. Compound 4e exhibited a dual mechanism by blocking both Na+ and Ca+2 channels.