Exploration of O-spiroketal C-arylglucosides as novel and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors.
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.
Lv
Binhua
B
Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, PR China. 51popo51@163.com
Xu
Baihua
B
Feng
Yan
Y
Peng
Kun
K
Xu
Ge
G
Du
Jiyan
J
Zhang
Lili
L
Zhang
Wenbin
W
Zhang
Ting
T
Zhu
Liangcheng
L
Ding
Haifeng
H
Sheng
Zelin
Z
Welihinda
Ajith
A
Seed
Brian
B
Chen
Yuanwei
Y
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
D001572:Benzofurans; D001786:Blood Glucose; D005960:Glucosides; D011714:Pyrans; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013141:Spiro Compounds