RESUMO
A series of 9H-xanthen-9-amines possessing a wide variety of nitrogen substituents at C-9 was prepared for evaluation of gastric antisecretory activity. These substituents included the acetamidine, imidate, pyrimidine, thiazoline, quinuclidine, 2-hydrazinopyridine, aminopiperidine, aminoalkylimidazole, and aminoalkylpyridine moieties. The majority of compounds in this series inhibited gastric acid secretion when tested orally in the pylorus-ligated rat. Potency was increased by intraduodenal administration and diminished by incubation with gastric juice, suggesting partial degradation of the compounds in the gastric environment. A representative example, 3-(9H-xanthen-9-ylamino)-1-ethylpiperidine, exhibited similar activity in dogs, although no free compound could be detected in the blood. It is therefore hypothesized that this compound is either rapidly bound to tissue and/or metabolized to an active species.
Assuntos
Ácido Gástrico/metabolismo , Xantenos/síntese química , Animais , Cães , Meia-Vida , Masculino , Pentagastrina/farmacologia , Ratos , Xantenos/farmacologiaRESUMO
A sensitive GLC assay for ticrynafen, a diuretic agent with uricosuric properties, and its two metabolites in urine, serum, and plasma is described. The method employs methylation of carboxylic acid groups and trimethylsilyation of the hydroxyl group on one metabolite that cannot otherwise be separated readily from ticrynafen as a simple methyl ester. Urinary output and serum or plasma levels of ticrynafen and its two metabolites were measured in specimens from human volunteers receiving one 250-mg tablet.
