Abstract
A series of highly active C-aryl glucoside SGLT2 inhibitors containing a biphenyl motif were designed and synthesized for biological evaluation. Among the compounds tested, compound 16l demonstrated high inhibitory activity against SGLT2 (IC50=1.9 nM) with an excellent pharmacokinetic profile. Further study indicated that the in vivo efficacy of compound 16l was comparable to that of dapagliflozin, suggesting that further development would be worthwhile.
Keywords:
Biphenyl; C-Aryl glucoside; SGLT2 inhibitor; Type 2 diabetes.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biphenyl Compounds / chemical synthesis
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Biphenyl Compounds / chemistry*
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Biphenyl Compounds / pharmacokinetics
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Glucose Tolerance Test
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Glucosides / chemical synthesis
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Glucosides / chemistry*
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Glucosides / pharmacokinetics
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Half-Life
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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 / pharmacokinetics
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Protein Binding
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Rats
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Rats, Sprague-Dawley
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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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2-(3-((1,1'-biphenyl)-4-ylmethyl)-4-methylphenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
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Biphenyl Compounds
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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
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diphenyl