title: Novel anti-inflammatory agents based on pyridazinone scaffold; design, synthesis and in vivo activity.
abstract: Herein, we report the design, synthesis, and pharmacological properties of a series of arylethenylpyridazinones 3a-h and arylethylpyridazinone derivatives 3k-i from the corresponding aryloxohexenoic 1a-e and aryloxohexanoic acids 2a,d, respectively. The synthesized compounds were tested for their anti-inflammatory activity in carrageenan-induced rat paw edema model. Compound 3j demonstrated the greatest in vivo activity with ED(50) equal to 17mumol compared with celecoxib with no ulceration on the gastric mucosa. Docking study of the synthesized compounds into the active site of COX-2 revealed a similar binding mode to RS-57067, a COX-2 inhibitor.
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt. abouzid@yahoo.com
authors.forename: Khaled
authors.initials: K
authors.lastname: Abouzid
authors.forename: Salma A
authors.initials: SA
authors.lastname: Bekhit
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002351:Carrageenan; D051546:Cyclooxygenase 2 / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D008024:Ligands; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D008024:Ligands; D011724:Pyridazines; C530728:RS-57067; D002351:Carrageenan; D051546:Cyclooxygenase 2