title: Synthesis and structure-activity relationships of thienylcyanoguanidine derivatives as potassium channel openers.
abstract: In our series of studies on potassium channel openers, several thienylcyanoguanidine 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 be 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.
authors.affiliation: New Drug Discovery Research Laboratory, Kanebo Ltd., Osaka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yoshiizumi
authors.forename: S
authors.initials: S
authors.lastname: Ikeda
authors.forename: N
authors.initials: N
authors.lastname: Nishimura
authors.forename: K
authors.initials: K
authors.lastname: Yoshino
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002432:Cecum; D004285:Dogs; D005260:Female; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D006168:Guinea Pigs; D007275:Injections, Intravenous; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D020110:Pinacidil; D015221:Potassium Channels / Q000819:agonists*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D006146:Guanidines; C110564:N-(5-bromo-3-thienyl)-N'-cyano-N''-tert-pentylguanidine; C110563:N-cyano-N'-(5-cyano-3-thienyl)-N''-tert-pentylguanidine; D015221:Potassium Channels; D013876:Thiophenes; D020110:Pinacidil; C004711:dicyandiamido