Research Center, Green Cross Corporation, 303 Bojeong-Dong, Giheung-Gu, Yongin, Gyeonggi-Do 446-770, Republic of Korea.
Bioorg Med Chem. 2011 Sep 15;19(18):5468-79. doi: 10.1016/j.bmc.2011.07.045. Epub 2011 Jul 28.
Novel macrocyclic C-aryl glucoside SGLT2 inhibitors were designed and synthesized. Two different synthetic routes of macrocyclization were adopted to prepare novel ansa SGLT2 inhibitors. Among the compounds tested, [1,7]dioxacyclopentadecine macrocycles possessing methylthiophenyl at the distal ring 40 or ethoxyphenyl at the distal ring 23 showed the best in vitro inhibitory activity in this series to date (40, IC(50)=0.778 nM and 23, IC(50)=0.899 nM) against hSGLT2.
新型大环 C-芳基葡萄糖苷 SGLT2 抑制剂被设计和合成。采用两种不同的大环化合成路线来制备新型ansa SGLT2 抑制剂。在所测试的化合物中，[1,7]二氧杂环十五烷大环，在远端环 40 位上具有甲基噻吩基，或在远端环 23 位上具有乙氧基苯基，表现出迄今为止该系列化合物中对 hSGLT2 的最佳体外抑制活性（40，IC50=0.778 nM 和 23，IC50=0.899 nM）。
