摘要
利用达格列净作为原料经过两条路线合成了3,6-二脱氧达格列净,其3,6-二脱氧的位置进一步经过了NOE技术确认,体外h SGLT2抑制试验和大鼠尿糖排泄试验表明,所合成的3,6-二脱氧达格列净几乎没有SGLT2抑制活性,说明SGLT2抑制剂结构中葡萄糖片段上3-OH和6-OH同时脱除会导致SGLT2抑制剂完全丧失活性。
3,6-Dideoxydapagliflozin （9） was synthesized by two routes starting from dapagliflozin, and 3,6- dideoxy functionality of 9 was further confirmed by NOE. In vitro inhibitory assay against hSGLT2 and rat urinary glucose excretion test found that 9 was almost completely inactive against hSGLT2, indicating that deletion of both 3- OH and 6-OH in the glucose moiety of SGLT2 inhibitors cannot be tolerated and would lead to complete loss of bioactivity.
出处
《化学通报》
CAS
CSCD
北大核心
2015年第7期638-643,共6页
Chemistry
基金
国家自然科学基金项目(21302141)
天津市应用基础与前沿技术研究计划项目(14JCQNJC12900和14JCZDJC33500)
铜仁学院博士启动基金项目(trxy DF1401)资助
