Amide derivatives of [6-(5-methyl-3-phenylpyrazole-1-yl)-3(2H)-pyridazinone-2-yl]acetic acids as potential analgesic and anti-inflammatory compounds.
In this study, amide derivatives of [6-(5-methyl-3-phenyl-pyrazole-1-yl)-3(2H)-pyridazinone-2-yl]acetic acid were synthesized and tested for their in vivo analgesic and anti-inflammatory activity by using the p-benzoquinone-induced writhing test and carrageenan-induced hind paw edema model, respectively. The analgesic and anti-inflammatory activity of the compounds 6a, 6d, 6e, 6g, 6h and 6m were more potent than that of aspirin as an analgesic and indomethacin as an anti-inflammatory drug, respectively. The other derivatives generally resulted in comparable activity to reference compounds. Inhibitor activity of the active compounds on cyclooxygenase isoforms was also investigated by using in vitro human whole blood assay and found that these derivatives did not exert their analgesic and anti-inflammatory activities through COX inhibition and other mechanisms might be involved.
Banoglu
Erden
E
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Ankara, Turkey. banoglu@gazi.edu.tr
Akoğlu
Cağla
C
Unlü
Serdar
S
Küpeli
Esra
E
Yeşilada
Erdem
E
Sahin
M Fethi
MF
D000085:Acetates / Q000737:chemistry* / Q000494:pharmacology; D000284:Administration, Oral; D000577:Amides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D000700:Analgesics / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D001241:Aspirin / Q000494:pharmacology; D016227:Benzoquinones / Q000008:administration & dosage / Q000009:adverse effects; D002351:Carrageenan / Q000008:administration & dosage; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D006614:Hindlimb; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007527:Isoenzymes / Q000096:biosynthesis / Q000097:blood; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D015394:Molecular Structure; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000097:blood; D011724:Pyridazines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D021281:Quantitative Structure-Activity Relationship
D000085:Acetates; D000577:Amides; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D007527:Isoenzymes; D008565:Membrane Proteins; D011724:Pyridazines; C004532:quinone; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D001241:Aspirin; D007213:Indomethacin