ortho-Substituted C-aryl glucosides as highly potent and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors.
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.
Xu
Baihua
B
Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan 610041, PR China. xubaihua2002@126.com
Feng
Yan
Y
Lv
Binhua
B
Xu
Ge
G
Zhang
Lili
L
Du
Jiyan
J
Peng
Kun
K
Xu
Min
M
Dong
Jiajia
J
Zhang
Wenbin
W
Zhang
Ting
T
Zhu
Liangcheng
L
Ding
Haifeng
H
Sheng
Zelin
Z
Welihinda
Ajith
A
Seed
Brian
B
Chen
Yuanwei
Y
D002460:Cell Line; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013329:Structure-Activity Relationship
D005960:Glucosides; D007004:Hypoglycemic Agents; C495674:SLC5A1 protein, human; C089180:SLC5A2 protein, human; D051269:Sodium-Glucose Transporter 1; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors