title: Synthesis of amide derivatives of [6-(3,5-dimethylpyrazol-1-yl)-3(2H)-pyridazinone-2-yl] acetic acid and their analgesic and anti-inflammatory properties.
abstract: A series of structurally different amide derivatives of [6-(3,5-dimethylpyrazol-1-yl)-3(2H)-pyridazinone-2-yl]acetic acid were prepared and tested for their analgesic and anti-inflammatory activity in vivo by using p-benzoquinone-induced writhing test and carrageenan-induced hind paw edema model, respectively. The analgesic and anti-inflammatory activity of the compounds 6a and 6b were equipotent, and 6m was more potent than acetyl salicylic acid (CAS 50-78-2) as an analgesic and indometacin (CAS 53-86-1) as an anti-inflammatory drug, respectively. The other amide derivatives and parent carboxylic acid molecule generally resulted in lower activity to reference compounds. Inhibitor activity of the active compounds on cyclooxygenase isoforms was also investigated by using in vitro COX inhibitor screening assay and found that these derivatives did not exert their analgesic and anti-inflammatory activities through COX inhibition and that other mechanisms might be involved.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Etiler, Ankara, Turkey. banoglu@gazi.edu.tr
authors.forename: Erden
authors.initials: E
authors.lastname: Banoğlu
authors.forename: Cağla
authors.initials: C
authors.lastname: Akoğlu
authors.forename: Serdar
authors.initials: S
authors.lastname: Unlü
authors.forename: Burcu Calişlkan
authors.initials: BC
authors.lastname: Ergün
authors.forename: Esra
authors.initials: E
authors.lastname: Küpeli
authors.forename: Erdem
authors.initials: E
authors.lastname: Yeşilada
authors.forename: M Fethi
authors.initials: MF
authors.lastname: Sahin
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D016227:Benzoquinones; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D013055:Spectrophotometry, Infrared; D013276:Stomach Ulcer / Q000139:chemically induced
chemical_list: C505493:(6-(3,5-dimethylpyrazol-1-yl)-3(2H)-pyridazinone-2-yl) acetic acid; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D007202:Indicators and Reagents; D011720:Pyrazoles; D011724:Pyridazines; C004532:quinone; D002351:Carrageenan