Synthesis and structure-activity relationships of thienylcyanoguanidine derivatives as potassium channel openers

Abstract

In our series of studies on potassium channel openers, several thienyleyanoguanidine derivatives were synthesized and evaluated for smooth muscle relaxation activity in vitro. Among the newly synthesized compounds, N-cyano-N'-(5-cyano-3-thienyl)-N'-tert-pentylguanidine (4b) and N-(5-bromo- 3-thienyl)-N'-cyano-N'-tert-pentylguanidine (4f) exhibited excellent activity which was proved to he based on potassium channel-opening action. Bioisosterism between benzene and thiophene ring was observed in the arylcyanoguanidines. After intravenous administration to dogs, 4b lowered the blood pressure more strongly than pinacidil.