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The primary structures of the O-glycosidically linked oligosaccharides isolated from glycoproteins GP I and GP II of Fusarium sp. M7-1 were established. The oligosaccharides released by alkaline borohydride treatment from the glycoproteins were purified by Bio-Gel P-4 and HPLC. This approach resulted in one monosaccharide and seven oligosaccharides. Their primary structures were resolved mainly by NMR spectrometry in combination with methylation mass spectrometry and fast atom bombardment mass spectrometry. The following structures have been determined. [formula: see text].

A new series of N-Substituted 2-(benzhydryl- and benzylsulfinyl)nicotinamides 7 and 8 were synthesized. Upon acid activation in the acidic environment of the parietal cell, these compounds are converted into their active forms, 2,3-dihydro-3-oxoisothiazolo[5,4-b]pyridines 5, which inhibit gastric H+/K(+)-ATPase. Inhibitory activities against [14C]aminopyrine accumulation stimulated by dibutyryl cAMP in isolated rabbit parietal cells in vitro and histamine-induced gastric acid secretion in pylorus-ligated rats by intraduodenal administration in vivo were evaluated, and the structure-activity relationships were examined. Among the compounds synthesized, 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(4-pyridyl)nicotinamide (8b) showed potent inhibitory activities in vitro and in vivo equivalent to those of omeprazole, a typical H+/K(+)-ATPase inhibitor. Moreover, 8b was much more stable at neutral and weakly acidic pH than omeprazole, lansoprazole, and pantoprazole. Compound 8b is considered to be a promising agent for treating acid-related gastrointestinal disorders.

Nicotinamide Derivatives as a New Class of Gastric H+/K+-ATPase Inhibitors. Part 1. Synthesis and Structure-Activity Relationships of N-Substituted 2-(Benzhydryl-and benzylsulfinyl)nicotinamides.-A series of title compounds, e.g. (IV), (VIII), (IX), and (X), is synthesized. Acid activation converts them into their active isothiazolopyridine form. In comparison to reference compound omeprazole (XI), nicotinamide (Xa) possesses equivalent inhibitory activities in vitro and in vivo, is much more stable at neutral and weakly acidic pH and, thus, is a promising agent for treating acid-related gastrointestinal disorders. -(TERAUCHI, H.; TANITAME, A.; TADA, K.; NAKAMURA, K.; SETO, Y.; NISHIKAWA, Y.; J. Med. Chem. 40 (1997) 3, 313-321; Discovery Res. Lab.,

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