title: COX-1/COX-2 inhibitors based on the methanone moiety.
abstract: This paper focuses on the synthesis and the in vitro testing of dual COX-1/COX-2 inhibitors. Starting from structures of non-steroidal anti-inflammatory drugs (NSAIDs) the diaryl methanone element was chosen as a lead. Modifications were carried out on this scaffold to obtain potent inhibitors of the COX enzymes. The N-(2-aroylphenyl)sulphonamides and -amides were studied in detail, and to consolidate the data evaluated the corresponding 3- and 4-regioisomers were also investigated. The potency and the enzyme selectivity were varied by structural modifications of the lead.
authors.affiliation: Institute of Pharmacy, Fachbereich Chemie und Pharmazie, Johannes Gutenberg University of Mainz, Staudingerweg 5, D-55099 Mainz, Germany. dannhrdt@mail.uni-mainz.de
authors.forename: Gerd
authors.initials: G
authors.lastname: Dannhardt
authors.forename: Bernd L
authors.initials: BL
authors.lastname: Fiebich
authors.forename: Johannes
authors.initials: J
authors.lastname: Schweppenhäuser
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D010078:Oxazines / Q000737:chemistry*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D010078:Oxazines; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases