1-Aryl-1H-pyrazole-5-acetic acids with antiinflammatory, analgesic and other activities.
Reaction of methyl 4-methoxy-2-dimethylaminomethylene-3-oxobutanoate with arylhydrazines gave methyl 1-aryl-5-(methoxymethyl)-1H-pyrazole-4-carboxylates 1 in high yields. Esters 1 were hydrolyzed to the relative carboxylic acids, which were converted by heating to 1-aryl-5-(methoxymethyl)-1H-pyrazoles 3 in good yields. Reaction of 3 with hydrobromic acid afforded the intermediate 1-aryl-5-(bromomethyl)-1H-pyrazoles, which were converted with potassium cyanide to 1-aryl-1H-pyrazole-5- acetonitriles, whose hydrolysis gave the required 1-aryl-1H-pyrazole-5-acetic acids. Some acids 5 showed a strong antiinflammatory and analgesic activity in rats and mice, respectively, as well as moderate antipyretic and in vito platelet antiaggregating effects.
Menozzi
G
G
Istituto di Scienze Farmaceutiche dell'Università, Genova, Italy.
Mosti
L
L
Schenone
P
P
D'Amico
M
M
Falciani
M
M
Filippelli
W
W
D000085:Acetates / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D002351:Carrageenan; D003094:Collagen / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013055:Spectrophotometry, Infrared
D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010975:Platelet Aggregation Inhibitors; D011720:Pyrazoles; D002351:Carrageenan; D003094:Collagen