Synthesis and pharmacological evaluation of 1-methyl-5-[substituted-4 (3H)-oxo-1,2,3-benzotriazin-3-yl]-1H-pyrazole-4-acetic acid derivatives.
Several new 1-methyl-5-[substituted-4-oxo-1,2,3-benzotriazin-3-yl] -1H-pyrazole-4-acetic acids and their ethyl ester derivatives were prepared. The compounds were tested for analgesic and antiinflammatory activities, acute toxicity, ulcerogenic effect, and as in vitro inhibitors of 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), since it is claimed that the inhibition of such an enzyme predicts in vivo antiinflammatory activity. Some compounds were more active than phenylbutazone in the phenylbenzoquinone and acetic acid peritonitis tests, and equiactive to the same drug in the carrageenin paw edema test. All the compounds inhibited the 3 alpha-HSD, but no correlation was observed with the paw edema inhibition values. The compounds proved to possess marginal or no ulcerogenic effect, as well as low systemic toxicity.
Daidone
G
G
Dipartimento di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Italy.
Maggio
B
B
Plescia
S
S
Raffa
D
D
Schillaci
D
D
Migliara
O
O
Caruso
A
A
Cutuli
V M
VM
Amico-Roxas
M
M
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D015096:3-Hydroxysteroid Dehydrogenases; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)