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.
Vittorio
F
F
Istituto di Chimica Farmaceutica e Tossicologica, Università di Catania, Italy.
Pappalardo
M S
MS
Ronsisvalle
G
G
Caruso
A
A
Leone
M G
MG
Amico-Roxas
M
M
D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis*; D001522:Behavior, Animal / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D005122:Exudates and Transudates / Q000187:drug effects; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010653:Phenylbutazone / Q000494:pharmacology / Q000633:toxicity; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced; D013843:Thiazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011724:Pyridazines; D013843:Thiazines; D010653:Phenylbutazone