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.
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.
Banoğlu
Erden
E
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Etiler, Ankara, Turkey. banoglu@gazi.edu.tr
Akoğlu
Cağla
C
Unlü
Serdar
S
Ergün
Burcu Calişlkan
BC
Küpeli
Esra
E
Yeşilada
Erdem
E
Sahin
M Fethi
MF
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
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