Synthesis and pharmacological evaluation of 3H-pyridazino[4,5-b][1,4]benzothiazin-4(10H)-one derivatives

The dialkylamino-alkylation of 3H-pyridazino[4,5-b][1,4]benzothiazin-4(10H)-one-5,5-dioxide 5 produced the 3-dialkylaminoalkyl-derivatives 6. To the same compounds we arrived by selective reduction of the corresponding N-oxides 4, derived from the oxidation of the 3-dialkylaminoalkyl-3H-pyridazino[4,5-b][1,4]benzothiazin-4(10H)-ones 3. Similarly, the oxidation of the 10-dialkylaminoalkyl analogues 8 afforded the corresponding derivatives 9. The synthesized compounds were tested, as hydrochlorides, for their analgesic and anti-inflammatory activities. The results showed that many of these compounds possess a very good analgesic activity, superior to that of phenylbutazone, apparently not related to the position and the peculiarities of the aminoalkylic side-chain. The anti-inflammatory activity was moderate, comparable only for 4 c to that of phenylbutazone. In the most active compounds a very low ulcerogenic potential and a high LD50 have been observed.