title: Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of novel triarylpyrazoline derivatives as selective COX-2 inhibitors.
abstract: A new series of triarylpyrazoline derivatives 8a-p containing the most important COX-2 pharmacophore (SO2CH3 or/and SO2NH2) were synthesized by reaction of propen-1-one derivatives 6a-h with different phenyl hydrazine hydrochloride derivatives 7a-b in aqueous ethanol. 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 than COX-1 isozyme and showed good in vivo anti-inflammatory activity. Compounds 8g, 8j and 8o showed the highest anti-inflammatory activity and were less ulcerogenic (Ulcer Index=6.85, 7.7, 5.92, respectively) than indomethacin (Ulcer Index=12.3) and comparable to celecoxib (Ulcer Index=4.85).
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. Electronic address: khaled.ahmed@pharm.bsu.edu.e.
authors.forename: Khaled R A
authors.initials: KR
authors.lastname: Abdellatif
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Abdelgawad
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
authors.forename: Madlen B
authors.initials: MB
authors.lastname: Labib
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
authors.forename: Taha H
authors.initials: TH
authors.lastname: Zidan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use; D000068579:Celecoxib / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D020128:Inhibitory Concentration 50; D011485:Protein Binding; D011720:Pyrazoles / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D051381:Rats; D013329:Structure-Activity Relationship; D014456:Ulcer / Q000473:pathology / Q000517:prevention & control
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000068579:Celecoxib
keywords: Anti-inflammatory; Cyclooxygenase-2 inhibitors; Pyrazoline