Exploration of SAR regarding glucose moiety in novel C-aryl glucoside inhibitors of SGLT2

A variety of modifications at the C-6 position on glucose were conducted in the present study to establish SAR on carbohydrate pharmacophore based on structure of potent thiazole 5. Among the compounds tested, deshydroxy 29 demonstrated the best in vitro inhibitory activity against hSGLT2 in this se...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2011-01, Vol.21 (2), p.742-746
Main Authors: Park, Eun-Jung, Kong, Younggyu, Lee, Jun Sung, Lee, Sung-Han, Lee, Jinhwa
Format: Article
Language:English
Subjects:
antagonists
chemical derivatives
Dapagliflozin
Diabetes
Diabetes Mellitus - drug therapy
Diabetes Mellitus - enzymology
Glucose
Glycosides - chemistry
Glycosides - pharmacology
Humans
Hypoglycemic Agents - chemistry
Hypoglycemic Agents - pharmacology
SGLT
sodium glucose transporter
Sodium-Glucose Transporter 2 - antagonists & inhibitors
Sodium-Glucose Transporter 2 - metabolism
structure-activity relationships
Thiazole
thiazoles
Thiazoles - chemistry
Thiazoles - pharmacology
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Summary:A variety of modifications at the C-6 position on glucose were conducted in the present study to establish SAR on carbohydrate pharmacophore based on structure of potent thiazole 5. Among the compounds tested, deshydroxy 29 demonstrated the best in vitro inhibitory activity against hSGLT2 in this series to date. In order to investigate SAR regarding glucose moiety in novel C-aryl glucoside SGLT2 inhibitors containing a thiazole motif, a series of chemical modifications on glucose was conducted to explore potential utility as a suitable replacement of glucose per se. Among the compounds prepared, deshydroxy 29 (IC 50 = 7.01 nM) demonstrated the best in vitro inhibitory activity against SGLT2 in this series to date. But, none of the compounds were better than the parent molecule 5 (IC 50 = 1.75 nM).
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2010.11.115