Lithocholyltaurine interacts with cholinergic receptors on dispersed chief cells from guinea pig stomach.

Although bile acids damage gastric mucosa, the mechanisms underlying tissue injury induced by these agents are not well understood. To determine whether bile acids alter gastric secretory function, we investigated the actions of sodium cholate, deoxycholate, lithocholate, and their taurine and glycine conjugates on a highly homogeneous population of gastric chief cells. Lithocholyltaurine (LCT), a particularly injurious bile acid, caused a threefold increase in pepsinogen secretion (detectable with 100 nM and maximal with 10 microM LCT).

Identification of an aldose reductase inhibitor site by affinity labeling.

Animal studies indicate that aldose reductase inhibitors represent a pharmacological method for inhibiting the onset of diabetic complications that is independent of blood sugar control. This has spurred the development of aldose reductase inhibitors (ARIs). To facilitate the rational development of more potent and direct ARIs, more specific knowledge of the structural and pharmacophoric requirements of the site at which ARIs interact are required.

Synthesis and properties of the derivatives of 2-alkylthio-4-oxo-3,4- (and -1,4)-dihydropyrido-[2,3-d]pyrimidine-5- and -6-carboxylic acids.

Condensation of diethyl 2-amino-6-methylpyridine-3,4-dicarboxylate (I) with the corresponding isothiocyanates afforded derivatives of ethyl 4-oxo-2-thioxo-1,2,3,4-tetrahydropyrido [2,3-d]pyrimidine-5-carboxylate (V-VII). Alkylation of (V), (VI) and (XI) gave the corresponding derivatives of ethyl 2-alkylthio-4-oxo-3,4-(and 1,4)-dihydropyrido[2,3-d]pyrimidine-5- and -6- carboxylate [(XII-XVI), (XX-XXII)]. Some of the obtained compounds were active pharmacologically.

Synthesis and properties of new derivatives of ethyl 7-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3-d]pyrimidine-5-carboxylate.

Condensation of diethyl 2-amino-6-methylpyridine-3,4-dicarboxylate with phenyl or cyclohexyl isocyanates gave the corresponding derivatives of ethyl 7-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3-d]pyrimidine- 5-carboxylate[(V), (VI)]. Alkylation of (V) and (VI) afforded the corresponding N-1 substituted derivatives (XI-XIX).

Synthesis and properties of new 3-acyl- and 3-carbamoyl derivatives of esters of 3H-2-imino-7-methyl-4-oxopyrido[3,2-e]-1,3-thiazine-5- and -6-carboxylic acids.

It was stated that esters of 3H-2-imino-7-methyl-4-oxopyrido[3,2-e]-1,3-thiazine-5- and -6-carboxylic acids react with acyl anhydrides and chlorides giving 3-acyl derivatives. Reaction of the above mentioned esters with isocyanates affords the corresponding 3-carbamoyl derivatives.

Investigations on the synthesis and properties of new derivatives of pyrido[3,2-e]-1,3-thiazino[3,2-a]-s-triazine.

It has been found that the condensation of esters of 3H-2-imino-7-methyl-4-oxopyrido[3,2-e]-1,3-thiazine-5- and -6-carboxylic acids (I, II) with formaldehyde and primary amines affords the corresponding derivatives of a new heterocyclic system pyrido[3,2-e]-1,3-thiazino [3,2-a]-s-triazine (IX-XXIV).