Synthesis of 3-substituted 2-oxo-1,4-thiazines and evaluation of their protective effect against endotoxin shock in mouse.

5-Methyl-2,3-dioxo-2H,4H-1,4-thiazine (7) was obtained by the oxidation of 5-methyl-2H-1,4-thiazin-3(4H)-one (5) with m-chloroperbenzoic acid in MeOH, followed by acid hydrolysis of the resulting 2,2-dimethoxy-1,4-thiazine (6). 3-Chloro-2-oxo-1,4-thiazine (10), which was obtained from 7 by heating with phosphorous oxychloride, reacted with various nucleophiles to give 3-substituted 2-oxo-1,4-thiazines (11a--y). Some of these 2-oxo-1,4-thiazines, 11a--b, e, o and r--s, showed a protective effect against endotoxin shock in D-galactosamine-sensitized mice.