Yoshiizumi K, Ikeda S, Nishimura N, Yoshino K
New Drug Discovery Research Laboratory, Kanebo Ltd., Osaka, Japan.
Chem Pharm Bull (Tokyo). 1997 Dec;45(12):2005-10. doi: 10.1248/cpb.45.2005.
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.
在我们关于钾通道开放剂的一系列研究中，合成了几种噻吩基氰基胍衍生物，并对其体外平滑肌舒张活性进行了评估。在新合成的化合物中，N-氰基-N'-(5-氰基-3-噻吩基)-N"-叔戊基胍（4b）和N-(5-溴-3-噻吩基)-N'-氰基-N"-叔戊基胍（4f）表现出优异的活性，事实证明其基于钾通道开放作用。在芳基氰基胍中观察到苯环和噻吩环之间的生物电子等排现象。给犬静脉注射后，4b降低血压的作用比吡那地尔更强。
