Synthesis of some novel pyrazole derivatives as potential antiinflammatory agents with minimum ulcerogenic activity.
Two novel isomeric series, N-substituted-5-amino-4-(3,4-dimethoxyphenyl)-3-hydroxy-1 H-pyrazole-1-carboxamides (or thiocarboxamides) 6a-e, 7a, b and N-substituted-3-amino-4-(3,4-dimethoxyphenyl)-5-hydroxy-1 H-pyrazole-1-carboxamides or (thiocarboxamides) 9a-c were synthesized. Moreover, the pyrazolo-[1,5-a]-1,3,5-triazine derivative 8 was also prepared. The new compounds were tested biologically for their in vivo antiinflammatory activity (AI) against carrageenan-induced rat paw oedema. All the investigated compounds exhibited significant AI activity in the range of 23-65%. The most potent compounds were further evaluated for their ulcerogenic liability and acute toxicity. They were found to be less toxic and nearly devoid of ulcerogenic activity as compared to phenylbutazone and indometacin.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Egypt.
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el-Hawash
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el-Mallah
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D005528:Foot / Q000473:pathology; D005753:Gastric Mucosa / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010653:Phenylbutazone / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D002351:Carrageenan; D010653:Phenylbutazone; D007213:Indomethacin