title: Synthesis and biological evaluation of some N-arylpyrazoles and pyrazolo[3,4-d]pyridazines as anti-inflammatory agents.
abstract: A series of 3,4-bis-chalcone-N-arylpyrazoles 3a-k was prepared from diacetyl pyrazoles 2a-e. The reaction of 2d and 2e with hydrazine hydrate gave pyrazolo[3,4-d]pyridazine derivatives 4a-b. Furthermore, the reaction of 2a-e with thiosemicarbazide afforded pyrazolo[3,4-d]pyridazine thiocyanate salts 5a-e. The synthesized compounds were subjected to in vivo anti-inflammatory and ulcerogenic activity measurements, in addition to determination of their in vitro COX selectivity, to give a full profile about their anti-inflammatory activities. Compounds 3c, 3f, 3i, and 3e showed significant anti-inflammatory activity among the synthesized compounds. Moreover, docking studies were performed to give an explanation for their anti-inflammatory activity through COX selectivity.
authors.affiliation: Faculty of Pharmacy, Pharmaceutical Chemistry Department, Taif University, Taif, Saudi Arabia. osamaelsabbagh@yahoo.com
authors.forename: Osama I
authors.initials: OI
authors.lastname: El-Sabbagh
authors.forename: Samia
authors.initials: S
authors.lastname: Mostafa
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Abdel-Aziz
authors.forename: Hany S
authors.initials: HS
authors.lastname: Ibrahim
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Elaasser
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D062105:Molecular Docking Simulation; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced
chemical_list: D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D011451:Prostaglandin-Endoperoxide Synthases
keywords: Anti-inflammatory activity; COX selectivity; Molecular docking; N-Aryl pyrazoles; Pyrazolopyridazine