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

Pharmazie. 1998 Jan;53(1):24-8.

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.

MeSH terms

  • Anesthetics, Local / chemical synthesis*
  • Anesthetics, Local / pharmacology
  • Anesthetics, Local / toxicity
  • Animals
  • Anti-Arrhythmia Agents / chemical synthesis*
  • Anti-Arrhythmia Agents / pharmacology
  • Anti-Arrhythmia Agents / toxicity
  • Arrhythmias, Cardiac / chemically induced
  • Arrhythmias, Cardiac / prevention & control
  • Calcium Chloride
  • Carticaine / chemistry
  • Carticaine / pharmacology
  • Cornea / drug effects
  • Guinea Pigs
  • Lethal Dose 50
  • Male
  • Ouabain
  • Rabbits
  • Rats
  • Rats, Wistar
  • Thiophenes / chemical synthesis*

Substances

  • Anesthetics, Local
  • Anti-Arrhythmia Agents
  • Thiophenes
  • Ouabain
  • Carticaine
  • Calcium Chloride