A Convenient Synthesis of N-Substituted 2,3-Dihydro-3-oxoisothiazolo[5,4-b]pyridines in Acidic Condition

A novel and convenient synthesis of N-substituted 2.3-dihydro-3oxoisothiazolo[5,4-blpyridines which possess potent in vitro inhibitory activity against gastric (H+/K+)-ATPase is reported.Compared with the methods reported previously, the compounds were synthesized more readily in relatively high yields by conversion of N-substituted 2-(benzyl-, 1-phenylethyl-, and benzhy~1suKmyl)nicotinamides (17d-I) in a diluted hydrochloric acid-methanol solution at room temperature.Recently, gastric (H+/K+)-ATPase inhibitors represented by 2-[(2-pyridyhethyl)sflmyl]benzimidazoles (PSBs) such as omeprazolel have been shown to be potent antiulcer agents.It is well known that the PSBs act as prodrugs, being chemically transformed to biologically active intermediates, sulfenamides, in acidic conditi~n.~On the basis of random screening, we have found that N-substituted 2.3-dihydro-3-oxoisothiazolo[5,4b]py~dines3 (1) and (2) inhibited the (H+/K+)-ATPase irreversibly,4 but did not exhibit inhibitory