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

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. A series of C-aryl glucosides with various substituents at the 4′-position of the distal aryl ring have been synthesized and eva...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2011-08, Vol.21 (15), p.4465-4470
Hauptverfasser: Xu, Baihua, Feng, Yan, Cheng, Huawei, Song, Yanli, Lv, Binhua, Wu, Yuelin, Wang, Congna, Li, Shengbin, Xu, Min, Du, Jiyan, Peng, Kun, Dong, Jiajia, Zhang, Wenbin, Zhang, Ting, Zhu, Liangcheng, Ding, Haifeng, Sheng, Zelin, Welihinda, Ajith, Roberge, Jacques Y., Seed, Brian, Chen, Yuanwei
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Sprache:eng
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Zusammenfassung: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. 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2011.06.032