2-Phenylpyrazolo[1,5-a]pyrimidin-7-ones. A new class of nonsteroidal antiinflammatory drugs devoid of ulcerogenic activity.
Syntheses of some pyrazolo[1,5-a]pyrimidines were performed in order to study the relationship between structural modifications on the parent 4,7-dihydro-2-phenylpyrazolo[1,5-a]pyrimidin-7-one (1) and their antiinflammatory properties. The modifications carried out were introduction and functionalization of a longer side chain at the 4-position, substitution of the hydrogen atom at the 3-position, and replacement of the phenyl group with a 4-methylphenyl, methyl, or hydrogen substituent. 4-Ethyl-4,7-dihydro-2-phenylpyrazolo [1,5-a]pyrimidin-7-one (3) showed the highest activity and a better therapeutic index than phenylbutazone and indomethacin, used as reference drugs. All other changes at the 3-, 5-, and 6-positions, as well as the replacement of the phenyl group at position 2, caused a marked decrease of activity. Compound 3 was found devoid of ulcerogenic activity and was probably endowed with antiulcerogenic properties.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000633:toxicity; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010653:Phenylbutazone / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000633:toxicity; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000633:toxicity; D051381:Rats; D014456:Ulcer / Q000139:chemically induced*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D011743:Pyrimidines; C039837:4-ethyl-4,7-dihydro-2-phenylpyrazolo(1,5-a)pyrimidin-7-one; D010653:Phenylbutazone; D007213:Indomethacin