Synthesis and structure-activity relationships of thienylcyanoguanidine derivatives as potassium channel openers.
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.
Yoshiizumi
K
K
New Drug Discovery Research Laboratory, Kanebo Ltd., Osaka, Japan.
Ikeda
S
S
Nishimura
N
N
Yoshino
K
K
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*
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