title: Analgesic agents without gastric damage: design and synthesis of structurally simple benzenesulfonanilide-type cyclooxygenase-1-selective inhibitors.
abstract: In order to create novel analgesic agents without gastric disturbance, structurally simple cyclooxygenase-1 (COX-1) inhibitors with a benzenesulfonanilide skeleton were designed and synthesized. As a result, compounds 11f and 15a, which possess a p-amino group on the benzenesulfonyl moiety and p-chloro group on the anilino moiety, showed COX-1-selective inhibition. Moreover compound 11f, which is the most potent compound in this study showed more potent analgesic activity than that of aspirin at 30 mg/kg by po. The anti-inflammatory activity and gastric damage, however, were very weak or not detectably different from aspirin. Since the structure of our COX-1 inhibitors are very simple, they may be useful as lead compounds for superior COX-1 inhibitors as analgesic agents without gastric disturbance.
authors.affiliation: Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 1-1-1, Tsushima-Naka, Okayama 700-8530, Japan.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Zheng
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Oda
authors.forename: Kayo
authors.initials: K
authors.lastname: Takamatsu
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tai
authors.forename: Eiichi
authors.initials: E
authors.lastname: Akaho
authors.forename: Hamed Ismail
authors.initials: HI
authors.lastname: Ali
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Oshiki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kakuta
authors.forename: Kenji
authors.initials: K
authors.lastname: Sasaki
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D000813:Anilides / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001557:Benzenesulfonates / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D002351:Carrageenan; D003124:Colorimetry; D018360:Crystallography, X-Ray; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005753:Gastric Mucosa / Q000473:pathology; D007202:Indicators and Reagents; D007213:Indomethacin / Q000633:toxicity; D007700:Kinetics; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D051381:Rats; D012756:Sheep; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D000813:Anilides; D001557:Benzenesulfonates; D016861:Cyclooxygenase Inhibitors; D007202:Indicators and Reagents; D002351:Carrageenan; D051545:Cyclooxygenase 1; D007213:Indomethacin