title: Chemical and pharmacological investigations on 2H-pyridazino[4,5-b] [1,4]benzothiazin-1(10H)-one derivatives.
abstract: 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.
authors.affiliation: Istituto di Chimica Farmaceutica e Tossicologica, Università di Catania, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Vittorio
authors.forename: M S
authors.initials: MS
authors.lastname: Pappalardo
authors.forename: G
authors.initials: G
authors.lastname: Ronsisvalle
authors.forename: A
authors.initials: A
authors.lastname: Caruso
authors.forename: M G
authors.initials: MG
authors.lastname: Leone
authors.forename: M
authors.initials: M
authors.lastname: Amico-Roxas
mesh_terms: 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
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011724:Pyridazines; D013843:Thiazines; D010653:Phenylbutazone