title: Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of new 1,3,5-triarylpyrazoline and 1,5-diarylpyrazole derivatives as selective COX-2 inhibitors.
abstract: Two new series of 1,3,5-triarylpyrazolines 10a-m and 1,5-diarylpyrazoles 14a-d were synthesized. All prepared compounds were evaluated for their in vitro COX-1/COX-2 inhibitory activity and the in vivo anti-inflammatory activity. All compounds were more selective for COX-2 isozyme and showed good in vivo anti-inflammatory activity. Compound 10k was the most COX-2 selective compound (S.I.=5.91) and the most potent anti-inflammatory derivative (ED50=99μmol/kg) which is approximately five folds more potent than ibuprofen (ED50=499μmol/kg) and had half potency of celecoxib (ED50=47μmol/kg). All compounds were less ulcerogenic (Ulcer Indexes=1.20-5.00) than ibuprofen (Ulcer Index=20.25) and comparable to celecoxib (Ulcer Index=2.90).
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. Electronic address: khaled.ahmed@pharm.bsu.edu.eg.
authors.forename: Khaled R A
authors.initials: KRA
authors.lastname: Abdellatif
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
authors.forename: Eman K A
authors.initials: EKA
authors.lastname: Abdelall
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
authors.forename: Wael A A
authors.initials: WAA
authors.lastname: Fadaly
authors.affiliation: Pharmacology Department, Faculty of Veterinary, Cairo University, Cairo, Egypt.
authors.forename: Gehan M
authors.initials: GM
authors.lastname: Kamel
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014456:Ulcer / Q000139:chemically induced
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: 1,5-Diarylpyrazole; Anti-inflammatory; Cyclooxygenase-2 inhibitors; Pyrazoline