1,2-Dihydro-2-oxo-6-(2,2-dimethylpropyl)-3-pyridinecarboxylic acid, analogues, and derivatives. A new class of oral hypoglycemic agents.

doi:10.1021/JM00150A008

Paper

1,2-Dihydro-2-oxo-6-(2,2-dimethylpropyl)-3-pyridinecarboxylic acid, analogues, and derivatives. A new class of oral hypoglycemic agents.

Published Dec 1, 1985 · G. A. Youngdale, T. F. Oglia

Journal of medicinal chemistry

Q1 SJR score

15

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0

Influential Citations

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Abstract

1,2-Dihydro-2-oxo-6-(2-methylpropyl)-3-pyridinecarboxylic acid was found to be a hypoglycemic agent but not to have the undesirable mechanism of action possessed by nicotinic acid. A series of 1,2-dihydro-2-oxo-3-pyridinecarboxylic acids with a substituent primarily at the 6-position was prepared by hydrolysis of the corresponding nitriles. The nitriles were prepared by reaction of the sodium enolate of the appropriate 3-substituted 3-oxopropionaldehyde with cyanoacetamide. The sodium enolates were synthesized from ethyl formate and the appropriate ketone and sodium or sodium hydride. The active 1,2-dihydro-2-oxo-3-pyridinecarboxylic acids, listed in order of decreasing hypoglycemic potency, had the following substituents: 6-(2,2-dimethylpropyl), 6-(2,2-dimethylbutyl), 6-(1,1-dimethylethyl), 6-(2-methylpropyl), 6-(1,1-dimethylpropyl), 1-methyl-6-(2-methylpropyl), 6-hydrogen. The inactive compounds were those with 6-methyl, 6-(1-methylethyl), 6-pentyl, 4-(2,2-dimethylpropyl), 6-(3-methylbutyl), 6-(1,1-dimethylheptyl), 6-(2,2-dimethyloctyl), 6-(1-cyclobutylmethyl), and 1-methyl-6-(2,2- dimethylpropyl) substituents. The corresponding alcohol, aldehyde, tetrazole, sodium salt, and ethyl ester of the most potent acid were also active compounds. The corresponding amide, decarboxyl compound, and 2-deoxo compound were inactive.

Study Snapshot

1,2-Dihydro-2-oxo-6-(2-methylpropyl)-3-pyridinecarboxylic acid is a new oral hypoglycemic agent with a unique mechanism of action, offering a promising alternative to nicotinic acid.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

1,2-Dihydro-2-oxo-6-(2,2-dimethylpropyl)-3-pyridinecarboxylic acid, analogues, and derivatives. A new class of oral hypoglycemic agents.

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References

Citations

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