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Omeprazole (5-methoxy-2-[[(4-methoxy-3,5- dimethylpyridinyl)methyl]sulfinyl]-1H-benzimidazole) appeared to inhibit gastric (H+-K+)-ATPase by oxidizing its essential sulfhydryl groups, since the gastric ATPase inactivated by the drug in vivo or in vitro recovered its K+-dependent ATP hydrolyzing activity upon incubation with mercaptoethanol. Biological(More)
3-Guanidinopropionic acid (1, PNU-10483) has been demonstrated to both improve insulin sensitivity and to promote weight loss selectively from adipose tissue in animal models of non-insulin-dependent diabetes mellitus (NIDDM). However, 1 has also been shown to be a substrate for both the creatine transporter and creatine kinase, leading to marked(More)
The synthesis of N-substituted benzimidazole (H(+)-K+)-ATPase or proton-pump inhibitors is described. These compounds were prepared to function as prodrugs of the parent N-H compound and evaluated for their ability to inhibit gastric (H(+)-K+)-ATPase and gastric acid secretion. The prodrugs reported rely on either in vivo esterase hydrolysis for liberation(More)
A number of PGE analogs have been synthesized in which the C-9 carbonyl group has been replaced by an exo-methylene group. These chemically stable 9-deoxo-9-methylene-PGEs exhibit biological profiles very similar to their less stable PGE relatives. 9-Deoxo-16,16-dimethyl-9-methylene-PGE2 (7) retains the useful uterine-stimulating potency of(More)
Oxygenation of pioglitazone-N-oxide by a microorganism isolated from soil was accompanied by N-deoxygenation to produce the pioglitazone metabolites 5-[4-[2-[5-(1-hydroxyethyl)-2-pyridyl]ethoxy]benzyl]-2,4-thiazolidinedio ne and 5-[4-[2-(5-acetyl-2-pyridyl)ethoxy]benzyl]2,4-thiazolidinedione. The oxygenating/deoxygenating organism has been characterized as(More)
This report describes the preparation of various 2,3-dinor-PGFalpha prostaglandins. Of particular importance is the synthesis of 2,3-dinor-15(S)-15-methyl PGF2alpha, the primary metabolite in the enzymatic degradation of 15(S)-15-methyl-PGF2alpha (1). Introduction of the three carbon beta,gamma-unsaturated carboxyl side chain was achieved in a one-step(More)
Ozonolysis of 6-oxo-PGF1alpha, 11,15-diacetate, methyl acetal, methyl ester followed by oxidative workup and treatment with diazomethane gave 3-acetoxy-5-hydroxy-2-(methoxycarbonyl) cyclopentane acetic acid, gamma-lactone and dimethyl 3-acetoxy-5[[-(methoxycarbonyl)valeryl]oxy]-1,2-cyclopentane dicarboxylate as two of the major products. The mass spectral(More)