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By by Helmut Buschmann (Editor), Thomas Christoph (Editor), Elmar Friderichs (Editor), Corinna Maul (Ed

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Diclofenac is combined with misoprostol to reduce gastrointestinal effects, which are the main side-effects. , 1999): The diazotation of 2,4-difluoroanaline with isoamyl nitrite and condensation with anisole gives 4-(2,4difluorophenyl)anisole, which is hydrolyzed with HI in refluxing acetic acid yielding 4-(2,4-difluorophenyl)phenol. Finally this compound is carbonated with K2CO3 and CO2 at 175 °C and 90 bar. ° w // NH? NO-O-C5HH HI, CH3COOH COX selectivity IC50 [MM] whole blood (1) H 2 CO 3 l CO 2 Scheme 13: Synthesis of diflunisal.

1996) (3) Penning etal. (1997) (4) Riendeau et al. (2001) (5) Chan etal. (1999) (6) Warner etal. (1999) (7) Talley et al. (2000a) Group first generation second generation third generation COX Inhibition Assays Inhibition of COX can be quantified in recombinant or natural enzyme preparations, cellular systems, isolated human cell populations such as platelets (COX-1) and white blood cells (COX-2), or in ex vivo stimulated whole blood samples The closer the experimental system is to the physiological state, the lower the selectivity for most COX-2-inhibitors.

The reaction product of indomethacin (see below) with benzyl bromo acetate can also be hydrogenated to Acemetacin. Clinical use: Acemetacin (Jacobi and Dell, 1980) is a nonsteroldal anti-inflammatory drug which acts directly via its major metabolite indomethacin. Acemetacin is used in chronic joint pain as well as in postoperative pain. The recommendation for oral dosing is between 120 and 360 mg daily. 04,Ar7p135°C /ex Scheme 5: Synthesis of acetylsalicylic acid. Clinical use: Acetylsalicylic acid is the prototype of a nonsteroidal anti-inflammatory drug and is used in a large number of inflammatory and pain indications Including musculoskeletal, soft tissue and joint disorders, headache, dysmenorrhoea and fever (Symposium on new perspectives on aspirin therapy 1983, various authors).

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