Abstract
Novel macrocyclic C-aryl glucoside SGLT2 inhibitors were designed and synthesized. Two different synthetic routes of macrocyclization were adopted to prepare novel ansa SGLT2 inhibitors. Among the compounds tested, [1,7]dioxacyclopentadecine macrocycles possessing methylthiophenyl at the distal ring 40 or ethoxyphenyl at the distal ring 23 showed the best in vitro inhibitory activity in this series to date (40, IC(50)=0.778 nM and 23, IC(50)=0.899 nM) against hSGLT2.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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CHO Cells
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Cell Line
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Cricetinae
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Cyclization
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Dose-Response Relationship, Drug
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Drug Design
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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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Macrocyclic Compounds / chemical synthesis
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Macrocyclic Compounds / chemistry
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Macrocyclic Compounds / pharmacology*
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Molecular Conformation
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Sodium-Glucose Transporter 2 / genetics
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Sodium-Glucose Transporter 2 / metabolism
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Sodium-Glucose Transporter 2 Inhibitors*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Glucosides
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Hypoglycemic Agents
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Macrocyclic Compounds
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SLC5A2 protein, human
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Sodium-Glucose Transporter 2
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Sodium-Glucose Transporter 2 Inhibitors