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.

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Xu B, Feng Y, Cheng H, Song Y, Lv B, Wu Y, Wang C, Li S, Xu M, Du J, Peng K, Dong J, Zhang W, Zhang T, Zhu L, Ding H, Sheng Z, Welihinda A, Roberge JY, Seed B, Chen Y

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.

Bioorg Med Chem Lett. 2011 Aug 1;21(15):4465-70. doi: 10.1016/j.bmcl.2011.06.032. Epub 2011 Jun 16.

PubMed ID

21737266 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Dapagliflozin	Sodium/glucose cotransporter 2	IC 50 (nM)	3100	N/A	N/A	Details