ortho-Substituted C-aryl glucosides as highly potent and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors

Baihua Xu; Yan Feng; Binhua Lv; Ge Xu; Lili Zhang; Jiyan Du; Kun Peng; Min Xu; Jiajia Dong; Wenbin Zhang; Ting Zhang; Liangcheng Zhu; Haifeng Ding; Zelin Sheng; Ajith Welihinda; Brian Seed; Yuanwei Chen

doi:10.1016/j.bmc.2010.04.088

ortho-Substituted C-aryl glucosides as highly potent and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors

Bioorg Med Chem. 2010 Jun 15;18(12):4422-32. doi: 10.1016/j.bmc.2010.04.088. Epub 2010 Apr 29.

Authors

Baihua Xu¹, Yan Feng, Binhua Lv, Ge Xu, Lili Zhang, Jiyan Du, Kun Peng, Min Xu, Jiajia Dong, Wenbin Zhang, Ting Zhang, Liangcheng Zhu, Haifeng Ding, Zelin Sheng, Ajith Welihinda, Brian Seed, Yuanwei Chen

Affiliation

¹ Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan 610041, PR China. xubaihua2002@126.com

PMID: 20576578
DOI: 10.1016/j.bmc.2010.04.088

Abstract

A series of 2-substituted C-aryl glucosides have been synthesized and evaluated for inhibition of hSGLT1 and hSGLT2. Introduction of an appropriate ortho substituent at the proximal phenyl ring adjacent to the glycosidic bond was found to improve SGLT2 inhibitory activity and dramatically increase selectivity for hSGLT2 over hSGLT1. Selected compounds were investigated for in vivo efficacy.

MeSH terms

Cell Line
Glucosides / chemical synthesis
Glucosides / chemistry*
Glucosides / pharmacology
Humans
Hypoglycemic Agents / chemical synthesis
Hypoglycemic Agents / chemistry*
Hypoglycemic Agents / pharmacology
Sodium-Glucose Transporter 1 / antagonists & inhibitors
Sodium-Glucose Transporter 1 / metabolism
Sodium-Glucose Transporter 2 / metabolism
Sodium-Glucose Transporter 2 Inhibitors*
Structure-Activity Relationship

Substances

Glucosides
Hypoglycemic Agents
SLC5A1 protein, human
SLC5A2 protein, human
Sodium-Glucose Transporter 1
Sodium-Glucose Transporter 2
Sodium-Glucose Transporter 2 Inhibitors