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Download Analgesics : from chemistry and pharmacology to clinical by Helmut Buschmann; Gregor Bahrenberg; et al PDF

By Helmut Buschmann; Gregor Bahrenberg; et al

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2001) Christoph and Buschmann 58 ci OH POCI3 . , e CI /PrOH HO 2-Chloro-3-hydroxy-propenal CI (COCI)2/DMF CI H 3 C. CH 3 NaOH/HPF6 0 iPr NH4OH 0 CI HO XV CI CI AcONH 4 /H + xviii H Ph. )LiHMDS,THF Scheme 20: Different cyclization pathways of of the ketosulfone to etoricoxib.

Chemical Classification of Selective COX-2 Inhibitors The large number of newly developed COX-2 Inhibitors demonstrates how promising this field of anti-Inflammatory agents is expected to be. More than 1000 COX-2 inhibitors have been described over the past few years (Prous database, March 2002). The chemical structures of COX-2 inhibitors are heterogenic. Contrary to the classical NSAIDs, this new class of enzyme inhibitors lacks a carboxylic acid group, thus effecting COX-2 affinity by a different orientation within the enzyme without formation of a salt bridge in the hydrophobia channel of the enzyme.

E. a methylsulfonyl moiety in combination with a halogen. This group of compounds is presently undergoing biological testing (Dannhardt and Kiefer, 2001). 38 Christoph and Buschmann hUC F F Figure 17: COX-2 Inhibitors with a diarylethylene moiety. Miscellaneous Structures Novel structural series that do not fit the above-mentioned categories have been Included In the miscellaneous group. Hoffmann-La Roche (Rotstein and Sjorgen (Hoffmann-La Roche), 1998) has described aroylnaphthalene derivatives, which exhibit good in vitro activity and selectivity.

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