Synthesis and biological evaluation of novel C-indolylxylosides as sodium-dependent glucose co-transporter 2 inhibitors.

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Yao CH, Song JS, Chen CT, Yeh TK, Hsieh TC, Wu SH, Huang CY, Huang YL, Wang MH, Liu YW, Tsai CH, Kumar CR, Lee JC

Synthesis and biological evaluation of novel C-indolylxylosides as sodium-dependent glucose co-transporter 2 inhibitors.

Eur J Med Chem. 2012 Sep;55:32-8. doi: 10.1016/j.ejmech.2012.06.053. Epub 2012 Jul 4.

PubMed ID

22818040 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Dapagliflozin	Sodium/glucose cotransporter 2	EC 50 (nM)	2.4	N/A	N/A	Details