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研究设计并以取代的苯甲酸为原料成功合成了一系列含有环丙烷结构的C-葡萄糖苷类钠-葡萄糖共转运子2(SGLT2)抑制剂,并对环丙烷部分的合成方法进行了研究,对所有化合物的结构经过了~1H NMR和HR-MS的表征.大鼠尿糖排泄(UGE)实验显示,所合成的7个含有环丙烷结构的C-葡萄糖苷类化合物1a~1g均显示较强的降血糖活性,其中(1S)-1-脱氧-1-{4-氯-3-[1-(4-乙氧基苯基)环丙-1-基]苯基}-D-葡萄糖(1e)的活性最强,但是仍比dapagliflozin低,显示出dapagliflozin的结构改造不能耐受环丙烷结构,且dapagliflozin中Cl原子的位置在类似物中是最优的.
A series of inhibitors of C-glucosidase sodium-glucose cotransporter 2 (SGLT2) containing cyclopropane were successfully synthesized and synthesized from substituted benzoic acid. The synthesis of cyclopropane was also studied. The structures of all the compounds were characterized by 1H NMR and HR-MS.Urinine excretion (UGE) assay showed that all of the seven cyclodextrin-containing C-glycosides 1a-1g Strong hypoglycemic activity in which (1S) -1-deoxy-1- {4-chloro-3- [1- (4-ethoxyphenyl) cycloprop-1-yl] phenyl} -D-glucose (1e) was the strongest but still lower than dapagliflozin, suggesting that the structural modification of dapagliflozin can not tolerate the cyclopropane structure and that the position of the Cl atom in dapagliflozin is optimal among the analogues.