SGLT-2抑制剂关键中间体及其衍生物的合成研究
Synthesis of Key Intermediates and Derivatives of SGLT-2 Inhibitors

SGLT-2抑制剂中芳基取代基是影响药物活性强弱的关键，本研究以恩格列净为先导化合物，对其芳基取代基进行修饰改造，设计合成4种新的SGLT-2抑制剂关键中间体，采用分子对接技术验证其设计合理性，经过酰氯化、亲电取代、亲核取代、还原四步反应合成出产率最高可达90.2%的SGLT-2抑制剂关键中间体。最终结构均经¹H-NMR、¹³C-NMR、HRMS联合验证。该路线具有操作简便、绿色高效、产率高的特点。为筛选出高活性SGLT-2抑制剂提供新思路。
The aryl substituents in SGLT-2 inhibitors are the key factors affecting the strength of drug activity. In this study, empagliflozin was taken as the lead compound, and its aryl substituents were modified and transformed to design and synthesize four new key intermediates of SGLT-2 inhibitors. The rationality of the design was verified by molecular docking technology. The key intermediates of SGLT-2 inhibitors with a maximum yield of 90.2% were synthesized through four-step reactions including acyl chlorination, electrophilic substitution, nucleophilic substitution and reduction. The final structures were all jointly verified by ¹H-NMR, ¹³C-NMR and HRMS. This synthetic route has the characteristics of simple operation, being environmentally friendly, highly efficient and having a high yield. It provides new ideas for screening out highly active SGLT-2 inhibitors.