Wu E S, Loch J T, Toder B H, Borrelli A R, Gawlak D, Radov L A, Gensmantel N P
Department of Chemistry, Fisons Pharmaceuticals, Rochester, New York 14623.
J Med Chem. 1992 Sep 18;35(19):3519-25. doi: 10.1021/jm00097a009.
A series of 2-alkylisoflavone derivatives 1 was prepared with the intent to study the importance of the phenyl group (at the 3-position) of the isoflavone in imparting antihypertensive activity and the substitution effects at the 2-position of isoflavone. With the exception of the 2-isopropyl analog, the antihypertensive activity of these compounds appears to have a slow onset and long duration. None of the analogs appears better than the corresponding flavone (3) and 3-phenylflavone (2) analogs. An unsuccessful attempt to correlate the relationship between antihypertensive activity and the calculated torsional angle of C2-C3-C1'-C2' is discussed. Antiinflammatory activities of these compounds along with 7-(oxypropylamine)flavones were also evaluated and found to be not very potent. The antiinflammatory activity appears to be sensitive to steric effects of the alkyl group on the nitrogen and of substituents at the 2-position of the isoflavones, while the hydroxyl group of the propanolamine side chain is not essential.
制备了一系列2-烷基异黄酮衍生物1，旨在研究异黄酮3位苯基在赋予降压活性方面的重要性以及异黄酮2位的取代效应。除2-异丙基类似物外，这些化合物的降压活性似乎起效缓慢且持续时间长。没有一种类似物比相应的黄酮（3）和3-苯基黄酮（2）类似物表现更好。讨论了将降压活性与计算得到的C2-C3-C1'-C2'扭转角之间的关系进行关联的一次不成功尝试。还评估了这些化合物以及7-（氧丙胺基）黄酮的抗炎活性，发现其活性不是很强。抗炎活性似乎对异黄酮氮原子上烷基的空间效应以及异黄酮2位取代基的空间效应敏感，而丙醇胺侧链的羟基并非必需。
