Cassidy F, Evans J M, Hadley M S, Haladij A H, Leach P E, Stemp G
SmithKline Beecham Pharmaceuticals, Harlow, Essex, England.
J Med Chem. 1992 May 1;35(9):1623-7. doi: 10.1021/jm00087a018.
The synthesis and antihypertensive activity of a series of novel 3-[(substituted-carbonyl)amino]-2H-1-benzopyran-4-ols, administered orally to spontaneously hypertensive rats, are described. Optimum activity in this series was observed for compounds with branched alkyl or branched alkylamino groups flanking the carbonyl or thiocarbonyl group (21, 31-33), which were approximately equipotent to cromakalim. Replacement of the 4-hydroxyl group by hydrogen, methoxy, or amino in this series only led to a slight reduction in potency. These observations are in marked contrast to the structure-activity relationships previously found for the 4-amidobenzopyran-3-ols. The antihypertensive activity of representative compounds 15 and 33 was attempted by preatreatment with glibenclamide, and thus these compounds may belong to the series of drugs which have been classified as potassium channel activators.
描述了一系列新型3-[(取代羰基)氨基]-2H-1-苯并吡喃-4-醇的合成及其对自发性高血压大鼠口服给药后的降压活性。对于羰基或硫代羰基两侧带有支链烷基或支链烷基氨基的化合物（21、31 - 33），在该系列中观察到了最佳活性，这些化合物的活性与克罗卡林大致相当。该系列中用氢、甲氧基或氨基取代4-羟基只会导致活性略有降低。这些观察结果与先前发现的4-酰胺基苯并吡喃-3-醇的构效关系形成了显著对比。通过用格列本脲预处理来尝试代表性化合物15和33的降压活性，因此这些化合物可能属于已被归类为钾通道激活剂的药物系列。
