title: C-aryl glucosides substituted at the 4'-position as potent and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes.
abstract: A series of C-aryl glucosides with various substituents at the 4'-position of the distal aryl ring have been synthesized and evaluated for inhibition of hSGLT1 and hSGLT2. Introduction of alkyl or alkoxy substituents at the 4'-position was found to improve SGLT2 potency, whereas introduction of a hydrophilic group at this position was deleterious. Compounds with alkoxy-, cycloalkoxy- or cycloalkenyloxy-ethoxy scaffolds exhibited good inhibitory activity and high selectivity toward SGLT2. Selected compounds were investigated for in vivo efficacy.
authors: Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan, PR China. baihuaxu@egretpharma.com
authors: Baihua
authors: B
authors: Xu
authors: Yan
authors: Y
authors: Feng
authors: Huawei
authors: H
authors: Cheng
authors: Yanli
authors: Y
authors: Song
authors: Binhua
authors: B
authors: Lv
authors: Yuelin
authors: Y
authors: Wu
authors: Congna
authors: C
authors: Wang
authors: Shengbin
authors: S
authors: Li
authors: Min
authors: M
authors: Xu
authors: Jiyan
authors: J
authors: Du
authors: Kun
authors: K
authors: Peng
authors: Jiajia
authors: J
authors: Dong
authors: Wenbin
authors: W
authors: Zhang
authors: Ting
authors: T
authors: Zhang
authors: Liangcheng
authors: L
authors: Zhu
authors: Haifeng
authors: H
authors: Ding
authors: Zelin
authors: Z
authors: Sheng
authors: Ajith
authors: A
authors: Welihinda
authors: Jacques Y
authors: JY
authors: Roberge
authors: Brian
authors: B
authors: Seed
authors: Yuanwei
authors: Y
authors: Chen
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; 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; D051269:Sodium-Glucose Transporter 1; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors