RESUMO
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.
Assuntos
Glicemia/metabolismo , Ácidos Nicotínicos/farmacologia , Animais , Fenômenos Químicos , Química , Jejum , Alimentos , Hipoglicemiantes , Ácidos Nicotínicos/síntese química , Ratos , Relação Estrutura-AtividadeRESUMO
Reaction of 2,3,4,5,6-pentafluorobenzyl bromide with N-hydroxyphthalimide produced N-(2,3,4,5,6-pentafluorobenzyloxy)phthalimide which, after hydrazinolysis and treatment with hydrogen chloride, yielded O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride. The latter compound was used to derivatize keto steroids for their analysis by electron-capture GLC.
