title: Synthesis and biological evaluation of novel C-indolylxylosides as sodium-dependent glucose co-transporter 2 inhibitors.
abstract: Sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors are the current focus on the indication for the management of hyperglycemia in diabetes. Here, a novel series of C-linked indolylxyloside-based inhibitors of SGLT2 has been discovered. Structure-activity relationship studies revealed that substituents at the 7-position of the indole moiety and a p-cyclopropylphenyl group in the distal position were necessary for optimum inhibitory activity. The pharmacokinetic study demonstrates that the most potent compound 1i is metabolically stable with a low clearance in rats. In further efficacy study, 1i is found to significantly lower blood glucose levels of streptozotocin (STZ)-induced diabetic rats.
authors: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 35053, Taiwan.
authors: Chun-Hsu
authors: CH
authors: Yao
authors: Jen-Shin
authors: JS
authors: Song
authors: Chiung-Tong
authors: CT
authors: Chen
authors: Teng-Kuang
authors: TK
authors: Yeh
authors: Tsung-Chih
authors: TC
authors: Hsieh
authors: Szu-Huei
authors: SH
authors: Wu
authors: Chung-Yu
authors: CY
authors: Huang
authors: Yu-Lin
authors: YL
authors: Huang
authors: Min-Hsien
authors: MH
authors: Wang
authors: Yu-Wei
authors: YW
authors: Liu
authors: Chi-Hui
authors: CH
authors: Tsai
authors: Chidambaram Ramesh
authors: CR
authors: Kumar
authors: Jinq-Chyi
authors: JC
authors: Lee
mesh_terms: D000818:Animals; D016466:CHO Cells; D060326:Chemistry Techniques, Synthetic; D006224:Cricetinae; D003412:Cricetulus; D004355:Drug Stability; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D006027:Glycosides; D007004:Hypoglycemic Agents; D051269:Sodium-Glucose Transporter 1; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C010807:xylosides