4-氨基酸取代苯并吡喃类钾通道开放剂的合成

Synthesis of Benzopyran Derivatives as Potassium Channel Openers(PCOs)

经 7步反应 ,合成了未见文献报道的 2 8个 4 位上以L 构型或D 构型的α 氨基酸取代的苯并吡喃类化合物 ,其中包括 6对已分离开的旋光纯的非对映异构体。离体扩血管活性实验表明 ,化合物 1 7bB、1 8bA的扩血管活性比 pinacidil强 1 0倍或以上 ,化合物 9b、1 5bB、1 6bA的扩血管活性与pinacidil相当 。

benzopyran derivatives were synthesized through a seven step synthesis.Every derivative was composed of a pair of diastereoisomers.Six pairs of diastereoisomers were separated into 12 compounds of optical purity.Those optically pure benzopyran derivatives might be useful in the research of pharmaceutical stereochemistry of potassium channel openers.All of those novel compounds retained the core,2,2 dimethyl and 3 hydroxyl of the lead compound,cromaklim.The main modifications were the acetylation of 4 amino of benzopyran with amino acids of L or D configuration. The vasodilatory effects of those novel compounds were evaluated on the isolated preparation derived from rat aorta precontracted with 25 mmol/L potassium chloride.The results were as follows:(1)The vasorelaxtions of benzopyran derivatives 17bB and 18bA were 10 times or more potent than those of control compound pinacidil.9b、15bB and 16bA were similar to pinacidil.Other benzopyran derivatives were weak or inactive;(2)All of the effective compounds could not relax the rat aorta precontracted with 80 mmol/L potassium chloride.The results showed that those effective compounds have the pharmacological characteristics of the potassium channel openers.