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.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Diabetes Mellitus, Type 2 / drug therapy*
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Glucosides / chemical synthesis
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Glucosides / chemistry*
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Glucosides / therapeutic use
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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 / therapeutic use
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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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Sodium-Glucose Transporter 1
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Sodium-Glucose Transporter 2
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Sodium-Glucose Transporter 2 Inhibitors