title: Exploration of O-spiroketal C-arylglucosides as novel and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors.
abstract: A series of novel O-spiroketal C-arylglucosides have been prepared and evaluated in cell-based functional assays for activity against human sodium-dependent glucose co-transporters 1 and 2 (SGLT1 and 2). The core spiro[isobenzofuran-1,2'-pyran] structure proved to be an effective scaffold for diversification and a number of compounds with single digit nanomolar potency and high selectivity have been synthesized. Compound 5a promoted glucosuria when administered in vivo in rats and produced a significant blood glucose reduction effect.
authors.affiliation: Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, PR China. 51popo51@163.com
authors.forename: Binhua
authors.initials: B
authors.lastname: Lv
authors.forename: Baihua
authors.initials: B
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.forename: Kun
authors.initials: K
authors.lastname: Peng
authors.forename: Ge
authors.initials: G
authors.lastname: Xu
authors.forename: Jiyan
authors.initials: J
authors.lastname: Du
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
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: D000818:Animals; D001572:Benzofurans / Q000737:chemistry* / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry* / Q000494:pharmacology; D006029:Glycosuria / Q000139:chemically induced; D006801:Humans; D011714:Pyrans / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013141:Spiro Compounds / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D001572:Benzofurans; D001786:Blood Glucose; D005960:Glucosides; D011714:Pyrans; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013141:Spiro Compounds