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

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

Volume: 10 Issue: 3

Author(s): Lingyu Zhang, Yuli Wang, Huaqiang Xu, Yongheng Shi, Bingni Liu, Qunchao Wei, Weiren Xu, Lida Tang, Jianwu Wang and Guilong Zhao

Affiliation:

Keywords: Dapagliflozin, deoxy, SGLT2 inhibitor, synthesis.

Abstract: 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.

Cite this article as:

Zhang Lingyu, Wang Yuli, Xu Huaqiang, Shi Yongheng, Liu Bingni, Wei Qunchao, Xu Weiren, Tang Lida, Wang Jianwu and Zhao Guilong, Discovery of 6-Deoxydapagliflozin as a Highly Potent Sodium-dependent Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes, Medicinal Chemistry 2014; 10 (3) . https://dx.doi.org/10.2174/15734064113096660051