胃泌素类似物的合成及初步生物活性的研究

THE SYNTHESIS OF GASTRIN ANALOGS AND PRELIMINARY STUDY ON THEIR BIOLOGICAL ACTIVITIES

采用液相合成法合成了６个胃泌素类似物，其中两个（Ⅵ、Ⅶ）未见文献报道。改进了合成中的关键中间体──四肽胃泌素（Ⅶ）的合成工艺，由原来的１５步反应，缩短到１０步，使总收率由原来的１５％提高到３５％。新设计的两个类似物，经狗胃灌流实验测定，均具刺激胃酸分泌的活性，提示：这类（Ⅵ、Ⅶ）化合物有可能为治疗胃肠道疾病的药物设计提供一种新的结构类型。

Six gastrin analogs were synthesized by the liquidphase synthetic method, among them two(Ⅺ,Ⅻ) haven't been reported yet.A new synthesis scheme was also designed for the tetragastrin(Ⅷ) which is a key intermediate in the synthesis of pentagastrin analogs,it simplified the synthetic work greatly shortened the reaction steps(from 15 to 10) and increased the yield (from 15%to 35%). The biological activity test showed that two new pentagastrin analogs all have acid-secreting activity by gastric perfusion test in the dog. This result indicates that the new type of structure could be used to design drug for treating gastrointestinal diseases.