Abstract
Novel series of 3-amino-N-(4-aryl-1,1-dioxothian-4-yl)butanamides and 3-amino-N-(4-aryltetrahydropyran-4-yl)butanamides were synthesized and evaluated as dipeptidyl peptidase IV (DPP-IV) inhibitors. Derivatives incorporating the 6-substituted benzothiazole group showed highly potent DPP-IV inhibitory activity. Oral administration of (3R)-3-amino-4-(2,4,5-trifluorophenyl)-N-{4-[6-(2-methoxyethoxy)benzothiazol-2-yl]tetrahydropyran-4-yl}butanamide (12u) reduced blood glucose excursion in an oral glucose tolerance test.
MeSH terms
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Administration, Oral
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Benzothiazoles / chemical synthesis*
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Benzothiazoles / pharmacology
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Blood Glucose / metabolism
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Chemistry, Pharmaceutical / methods
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Dipeptidyl Peptidase 4 / chemistry*
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Dipeptidyl-Peptidase IV Inhibitors* / chemical synthesis*
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Dipeptidyl-Peptidase IV Inhibitors* / pharmacology
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Gastric Emptying
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Glucagon-Like Peptide 1 / chemistry
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Glucose Tolerance Test
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Humans
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Inhibitory Concentration 50
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Insulin-Secreting Cells / metabolism
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Models, Chemical
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Pyrans / chemistry*
Substances
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3-amino-4-(2,4,5-trifluorophenyl)-N-(4-(6-(2-methoxyethoxy)benzothiazol-2-yl)tetrahydropyran-4-yl)butanamide
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Benzothiazoles
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Blood Glucose
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Dipeptidyl-Peptidase IV Inhibitors
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Enzyme Inhibitors
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Pyrans
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Glucagon-Like Peptide 1
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Dipeptidyl Peptidase 4