Synthesis and Cardiovascular Activity of Phenylalkylamine Derivatives. I. Potential Specific Bradycardic Agents

• Published in: Chemical & pharmaceutical bulletin Vol. 40; no. 10; pp. 2735 - 2740
• Main Authors: OZAKI, Fumihiro, MATSUKURA, Masayuki, KABASAWA, Yasuhiro, ISHIBASHI, Keiji, IKEMORI, Megumi, HAMANO, Sachiyuki, MINAMI, Norio
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1992; Maruzen; Japan Science and Technology Agency
• Subjects: (E)-N-[3-[N'-[2-(3, 4-dimethoxyphenyl)ethyl]-N'-methylamino]propyl]-4-[3, 4-(methylenedioxy)phenyl]-3-butenamide; 4-(substituted phenyl)-3-butenoic acid; angina pectoris; Animals; Bradycardia - chemically induced; bradycardic activity; Cardiotonic Agents - chemical synthesis; Cardiotonic Agents - pharmacology; Chemistry; Dogs; Exact sciences and technology; Female; Guinea Pigs; Male; N-(ω-aminoalkyl)-N-methylhomoveratrylamine; Noncondensed benzenic compounds; Organic chemistry; Preparations and properties; structure-activity relationships; Verapamil - analogs & derivatives; Verapamil - chemical synthesis; Verapamil - pharmacology; Fissipedia; Carnivora; In vitro; Vertebrata; Bradycardia; Mammalia; Structure activity relation; Aminoacid; Animal; Vinylic compound; Benzenic compound; Dog; Antiarrhythmia agent
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.40.2735

A series of acyclic amide derivatives of N-(ω-aminoalkyl)-N-methylhomoveratrylamine was synthesized and evaluated for their bradycardic activity in isolated guinea pig right atria. Among these compounds, (E)-N-[3-[N'-2-(3, 4-dimethoxyphenyl)ethyl]-N'-methylamino]propyl]-4-[3, 4-(methylenedioxy)phenyl]-3-butenamide (35) was the most potent in vitro and was also found to show dose-dependent bradycardia without remarkable reduction of left ventricular dp/dtmax or mean aortic pressure in anesthetized dogs.