Synthesis and Structure-Activity Relationships of Novel Phenylcyanoguanidine Derivatives as Potassium Channel Openers
| Autor: | Kazuya Yoshizumi, Kohichiro Yoshino, Tominori Morita, Takayuki Sukamoto, Shoji Ikeda, Noriyasu Nishimura, Katsumi Goto |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Magnetic Resonance Spectroscopy Potassium Channels Stereochemistry Muscle Relaxation Vasodilator Agents Guinea Pigs Blood Pressure In Vitro Techniques Guanidines Chemical synthesis Structure-Activity Relationship chemistry.chemical_compound Heart Rate Ileum Oral administration Rats Inbred SHR Glyburide Drug Discovery Animals Hypoglycemic Agents Alkyl chemistry.chemical_classification Pinacidil Muscle Smooth General Chemistry General Medicine Potassium channel Rats chemistry Nitro Potassium channel opener Pharmacophore |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 44:2042-2050 |
| ISSN: | 1347-5223 0009-2363 |
| Popis: | 3, 5-Di-substituted phenylcyanoguanidine derivatives with halogen, cyano, and/or nitro groups at the 3- and 5-positions of the benzene ring exhibited very strong smooth muscle relaxation activity in vitro, as compared to pinacidil. Among them, N-(3-chloro-5-cyanophenyl)-N'-cyano-N"-tert-pentylguanidine (5s) showed 27-fold more potent activity than pinacidil, and exhibited a stronger and more lasting antihypertensive effect than pinancidil by oral administration to spontaneously hypertensive rats. We propose a new pharmacophore model in which the essential factors for binding to the potassium channel are an NH and a bulky alkyl group. |
| Databáze: | OpenAIRE |
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