Chemical and pharmacological investigations on 2H-pyridazino[4,5-b] [1,4]benzothiazin-1(10H)-one derivatives

The methylation of 2H-pyridazino [4,5-b][1,4]benzothiazin-1(10H)-one-5,5-dioxide 2 and the oxidation of 2-methyl-2H-pyridazino[4,5-b][1,4]benzothiazin-1(10H)-one 3 produced the same compound 4. On the contrary, in the 2-dialkylaminoalkylic series, the dialkylamino-alkylation and the oxidation reactions, carried out on compounds 2 and 8 respectively, afforded derivatives 7 and 9. In addition, the behaviour to the oxidation of the corresponding 10-methyl and 10-dialkylaminoalkyl analogues is also described. The synthesized compounds were tested for their analgesic, antiexudative and anti-inflammatory activities. The pharmacological results showed that in general dialkylaminoalkyl derivatives are more active than methyl derivatives. In particular, compounds 7 b, 9 b and 11 c exhibited an analgesic activity comparable to that of phenylbutazone; moreover 10-substituted compounds 11 a, 11 b and 11 c, screened p.o. as anti-inflammatory agents in rats, resulted equipotent to phenylbutazone and more active than 2-substituted isomers. These activities are coupled with a high LD50 and a very low ulcerogenic potential.