Abstract
A series of 2-substituted C-aryl glucosides have been synthesized and evaluated for inhibition of hSGLT1 and hSGLT2. Introduction of an appropriate ortho substituent at the proximal phenyl ring adjacent to the glycosidic bond was found to improve SGLT2 inhibitory activity and dramatically increase selectivity for hSGLT2 over hSGLT1. Selected compounds were investigated for in vivo efficacy.
Copyright 2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Cell Line
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Glucosides / chemical synthesis
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Glucosides / chemistry*
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Glucosides / pharmacology
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Humans
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Hypoglycemic Agents / chemical synthesis
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Hypoglycemic Agents / chemistry*
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Hypoglycemic Agents / pharmacology
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Sodium-Glucose Transporter 1 / antagonists & inhibitors
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Sodium-Glucose Transporter 1 / metabolism
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Sodium-Glucose Transporter 2 / metabolism
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Sodium-Glucose Transporter 2 Inhibitors*
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Structure-Activity Relationship
Substances
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Glucosides
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Hypoglycemic Agents
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SLC5A1 protein, human
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SLC5A2 protein, human
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Sodium-Glucose Transporter 1
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Sodium-Glucose Transporter 2
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Sodium-Glucose Transporter 2 Inhibitors