Discovery of 6-Deoxydapagliflozin as a Highly Potent Sodium-dependent Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes

作者：Zhang, Lingyu; Wang, Yuli; Xu, Huaqiang; Shi, Yongheng; Liu, Bingni; Wei, Qunchao; Xu, Weiren; Tang, Lida; Wang, Jianwu^*; Zhao, Guilong

来源：Medicinal Chemistry, 2014, 10(3): 304-317.

DOI：10.2174/15734064113096660051

• Dapagliflozin
• deoxy
• SGLT2 inhibitor
• synthesis.

Systematic mono-deoxylation of the four hydroxyl groups in the glucose moiety in dapagliflozin led to the discovery of 6-deoxydapagliflozin 1 as a more active sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor (IC50 = 0.67 nM against human SGLT2 (hSGLT2) vs 1.16 nM for dapagliflozin). It exhibited more potent blood glucose inhibitory activity in rat oral glucose tolerance test and induced more urinary glucose in rat urinary glucose excretion test than its parent compound dapagliflozin.

• 出版日期2014-5
• 单位天津药物研究院有限公司; 天津医科大学; 山东大学