title: ortho-Substituted C-aryl glucosides as highly potent and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors.
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.
authors.affiliation: Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan 610041, PR China. xubaihua2002@126.com
authors.forename: Baihua
authors.initials: B
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.forename: Binhua
authors.initials: B
authors.lastname: Lv
authors.forename: Ge
authors.initials: G
authors.lastname: Xu
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Jiyan
authors.initials: J
authors.lastname: Du
authors.forename: Kun
authors.initials: K
authors.lastname: Peng
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Jiajia
authors.initials: J
authors.lastname: Dong
authors.forename: Wenbin
authors.initials: W
authors.lastname: Zhang
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Liangcheng
authors.initials: L
authors.lastname: Zhu
authors.forename: Haifeng
authors.initials: H
authors.lastname: Ding
authors.forename: Zelin
authors.initials: Z
authors.lastname: Sheng
authors.forename: Ajith
authors.initials: A
authors.lastname: Welihinda
authors.forename: Brian
authors.initials: B
authors.lastname: Seed
authors.forename: Yuanwei
authors.initials: Y
authors.lastname: Chen
mesh_terms: 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
chemical_list: 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