title: Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of new 1,5-diarylpyrazole derivatives.
abstract: A new series of 1,5-diarylpyrazoles 10a-l was designed and synthesized for evaluation as COX inhibitors and as anti-inflammatory agents. All compounds were more selective for COX-2 isozyme and showed good in vivo anti-inflammatory activity. Compound 10e was the most COX-2 selective compound (S.I. = 10.67) and the most potent anti-inflammatory derivative (ED50= 46 μmol/kg) which is approximately 11-folds more potent than ibuprofen (ED50= 499 μmol/kg) and had 2/3 potency of celecoxib (ED50= 31 μmol/kg). All compounds were less ulcerogenic (ulcer indexes = 1.20-4.61) than ibuprofen (ulcer index = 20.25) and comparable to celecoxib (ulcer index = 2.90).
authors.affiliation: a Department of Pharmaceutical Organic Chemistry , Beni-Suef University , Beni-Suef , Egypt.
authors.forename: Khaled R A
authors.initials: KR
authors.lastname: Abdellatif
authors.affiliation: a Department of Pharmaceutical Organic Chemistry , Beni-Suef University , Beni-Suef , Egypt.
authors.forename: Wael A A
authors.initials: WA
authors.lastname: Fadaly
authors.affiliation: b Biochemistry Department, Cairo General Hospital , Cairo , Egypt , and.
authors.forename: Waleed A M
authors.initials: WA
authors.lastname: Ali
authors.affiliation: c Pharmacology Department, Faculty of Veterinary, Cairo University , Cairo , Egypt.
authors.forename: Gehan M
authors.initials: GM
authors.lastname: Kamel
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013276:Stomach Ulcer / Q000139:chemically induced*; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D051546:Cyclooxygenase 2
keywords: 1,5-diarylpyrazole; Anti-inflammatory; cyclooxygenase-2 inhibitors