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.
Vittorio
F
F
Istituto di Chimica Farmaceutica e Tossicologica, Università di Catania, Italy.
Pappalardo
M S
MS
Ronsisvalle
G
G
Caruso
A
A
Cutuli
V M
VM
Amico-Roxas
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013055:Spectrophotometry, Infrared; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011724:Pyridazines; D013843:Thiazines