Amide Derivatives of [6-(5-Methyl-3-phenylpyrazole-1-yl)-3(2H)-pyridazinone-2-yl]acetic Acids as Potential Analgesic and Anti-Inflammatory Compounds

• Published in: Archiv der Pharmazie (Weinheim) Vol. 337; no. 1; pp. 7 - 14
• Main Authors: Banoglu, Erden, Akoğlu, Çağla, Ünlü, Serdar, Küpeli, Esra, Yeşilada, Erdem, Şahin, M. Fethi
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01-01-2004; WILEY‐VCH Verlag; Wiley-VCH
• Subjects: Acetates - chemistry; Acetates - pharmacology; Administration, Oral; Amides - administration & dosage; Amides - chemical synthesis; Amides - pharmacokinetics; Analgesic; Analgesics; Analgesics - administration & dosage; Analgesics - chemical synthesis; Analgesics - pharmacokinetics; Animals; Anti-Inflammatory; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Aspirin - pharmacology; Benzoquinones - administration & dosage; Benzoquinones - adverse effects; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Carrageenan - administration & dosage; COX-1; COX-2; Cyclooxygenase 1; Cyclooxygenase 2; Edema - chemically induced; Edema - prevention & control; Hindlimb; Humans; Indomethacin - pharmacology; Injections, Intraperitoneal; Isoenzymes - biosynthesis; Isoenzymes - blood; Male; Medical sciences; Membrane Proteins; Mice; Molecular Structure; Neuropharmacology; Pain - chemically induced; Pain - prevention & control; Pain Measurement - drug effects; Pain Measurement - methods; Pharmacology. Drug treatments; Prostaglandin-Endoperoxide Synthases - biosynthesis; Prostaglandin-Endoperoxide Synthases - blood; Pyridazines - administration & dosage; Pyridazines - chemical synthesis; Pyridazines - pharmacokinetics; Pyridazinone; Quantitative Structure-Activity Relationship; COX-2; Enzyme; COX-1; Cyclooxygenase 2; Rodentia; Antiinflammatory agent; Cyclooxygenase 1; Enzyme inhibitor; Anti-Inflammatory; Amides; Acetic acid derivative; In vitro; In vivo; Vertebrata; Mammalia; Analgesic; Structure activity relation; Mouse; Animal; Pyrazole derivatives; Pyridazine derivatives; Pyridazinone; Oxidoreductases; Chemical synthesis
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.200200738

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.