Abstract
A novel series of N-linked β-D-xylosides were synthesized and evaluated for inhibitory activity against sodium-dependent glucose cotransporter 2 (SGLT2) in a cell-based assay. Of these, the 4-chloro-3-(4-cyclopropylbenzyl)-1-(β-D-xylopyranosyl)-1H-indole 19m was found to be the most potent inhibitor, with an EC(50) value similar to that of the natural SGLT2 inhibitor phlorizin. Further studies in Sprague-Dawley (SD) rats indicated that 19m significantly increased urine glucose excretion in a dose-dependent manner with oral administration. The antihyperglycemic effect of 19m was also observed in streptozotocin (STZ) induced diabetic SD rats. These results described here are a good starting point for further investigations into N-glycoside SGLT2 inhibitors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CHO Cells
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Cricetinae
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Cricetulus
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Diabetes Mellitus, Experimental / blood
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Diabetes Mellitus, Experimental / drug therapy*
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Diabetes Mellitus, Experimental / urine
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Diabetes Mellitus, Type 2 / blood
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Diabetes Mellitus, Type 2 / drug therapy*
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Diabetes Mellitus, Type 2 / urine
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Glucose / metabolism
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Glucosides / chemical synthesis*
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Glucosides / pharmacokinetics
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Glucosides / pharmacology
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Humans
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Hyperglycemia / drug therapy*
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Hypoglycemic Agents / chemical synthesis*
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Hypoglycemic Agents / pharmacokinetics
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Hypoglycemic Agents / pharmacology
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Indoles / chemical synthesis*
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Indoles / pharmacokinetics
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Indoles / pharmacology
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Male
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Mice
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Mice, Inbred ICR
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Rats
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Rats, Sprague-Dawley
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Sodium-Glucose Transporter 2 Inhibitors*
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Structure-Activity Relationship
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Xylose / analogs & derivatives*
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Xylose / chemical synthesis
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Xylose / pharmacokinetics
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Xylose / pharmacology
Substances
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4-chloro-3-(4-cyclopropylbenzyl)-1-(xylopyranosyl)-1H-indole
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Glucosides
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Hypoglycemic Agents
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Indoles
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Sodium-Glucose Transporter 2 Inhibitors
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Xylose
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Glucose