Abstract
Vesicular monoamine transporter type 2 (VMAT2) is a newly emerging target for both diagnostic and therapeutic applications in diabetes mellitus. In pursuit of novel VMAT2 antagonists, we identified a potent hypoglycemic agent with a novel dihydropyridone scaffold. Several analogs were designed and synthesized. A preliminary structure activity relationship (SAR) showed that the dihydropyridone scaffold is required for the activity.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Alkylation
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Animals
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Diabetes Mellitus / diagnosis
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Diabetes Mellitus / drug therapy*
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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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Male
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Molecular Structure
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Pyridones / chemical synthesis*
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Pyridones / chemistry
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Pyridones / pharmacology*
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Rats
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Rats, Inbred Lew
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Structure-Activity Relationship
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Tetrabenazine / analogs & derivatives*
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Tetrabenazine / pharmacology
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Vesicular Monoamine Transport Proteins / antagonists & inhibitors*
Substances
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Hypoglycemic Agents
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Pyridones
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Vesicular Monoamine Transport Proteins
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dihydrotetrabenazine
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Tetrabenazine