1-phenyl-1H-pyrazole derivatives with antiinflammatory, analgesic and antipiretic activities.
Reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates 2 with phenylhydrazine gave the corresponding esters of 5-substituted 1-phenyl-1H-pyrazole-4-carboxylic acids 3 in high yields. Esters 3 were hydrolyzed to the relative carboxylic acids 4, which were converted by heating to 5-substituted 1-phenyl-1H-pyrazoles 5 in excellent yields. Reaction of methyl 5,5-dimethyl-3-dimethylaminomethylene-2,4-dioxohexanoate with phenylhydrazine afforded methyl 1-phenyl-4-pivaloyl-1H-pyrazole-5-carboxylate 8 b, which was converted as above to the corresponding carboxylic acid 10 b and this to 1-phenyl-4-pivaloyl-1H-pyrazole 11 b. Starting from 5-methoxymethyl-1-phenyl-1H-pyrazole, 1-phenyl-1H-pyrazole-5-acetic acid 18 and its alpha-methyl derivative 19 were also synthesized. Compounds 18, 19, 10 b and 11 b showed a strong antiinflammatory activity in rats; the same compounds in general as well as 8 b, showed appreciable analgesic and antipyretic activities in mice and rats, respectively.
Menozzi
G
G
Istituto di Scienze Farmaceutiche dell'Università, Genova, Italy.
Mosti
L
L
Schenone
P
P
Donnoli
D
D
Schiariti
F
F
Marmo
E
E
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control; D005528:Foot / Q000473:pathology; D051379:Mice; D010147:Pain Measurement; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D015002:Yeast, Dried
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D002351:Carrageenan