含噻二唑环的硫代糖苷类SGLT2抑制剂的设计、合成与降血糖活性研究  

Design,Synthesis and Anti-diabetic Activity of Thiadiazole-Based Thioglycosides as SGLT2 Inhibitors

作　　者：王致峰[1] 赵桂龙[2] 刘巍[2] 王玉丽[2] 邵华[2] 徐为人[2] 田来进[1] 

机构地区：[1]曲阜师范大学化学与化工学院,曲阜273165 [2]天津药物研究院分子设计与药物发现天津市重点实验室,天津300193

出　　处：《有机化学》2010年第6期849-859,共11页Chinese Journal of Organic Chemistry

基　　金：科技部支撑(No.2007BAI40B01);天津市科技支撑计划重点(No.10ZCKFSH01300)资助项目

摘　　要：在相转移催化剂BnEt3N+Br-作用下,利用5-取代苯氧甲基-2-巯基-1,3,4-噻二唑与α-溴代四乙酰基吡喃糖室温反应,合成了22个结构新颖的硫代糖苷类SGLT2抑制剂化合物,结构经IR,1HNMR,13CNMR和HR-ESI-MS谱表征确认.采用小鼠口服葡萄糖耐受量法测定了目标化合物在治疗糖尿病方面的活性,结果发现化合物9Ah有明显的降糖作用,而9Aa和9Bi与对照药物格列齐特相当.22 thioglycosides with novel structure were designed and synthesized from 5-substituded phenyloxymethyl-2-mercapto-1,3,4-thiadiazole and tetra-O-acetyl-α-glycopyranosyl bromides in the presence of phase transfer catalysis（BnEt3N^＋Br^-） at room temperature.These compounds were characterized by IR,^1H NMR,^13C NMR,and HR-ESI-MS techniques.Bioactivity of decreasing blood glucose was performed through in vivo by oral glucose tolerance test（OGTT） in mice.In addition,preliminary pharmacological test showed that compound 9Ah was more potent than positive control gliclazide,while compounds 9Aa and 9Bi were comparable to gliclazide in potency.

关 键 词：噻二唑 硫代糖苷 SGLT2抑制剂 合成 降糖活性 

分 类 号：R91[医药卫生—药学]