By Helmut Buschmann; Gregor Bahrenberg; et al
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Additional resources for Analgesics : from chemistry and pharmacology to clinical application
2001). 57 COX selectivity IC50 [MM] recomb. 1 105 (D cellular assay (D whole blood (1) (1) Riendeau etal. (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.
The metabolites of diclofenac, 4'-hydroxydiclofenac, 5-hydroxydiclofenac, 3'-hydroxy-diclofenac, and 4',5-dihydroxydiclofenac are excreted as glucuronide and sulphate conjugates in the urine (-65%) and in the bile (-35%). 49 COX selectivity IC50 [MM] COX-1 COX-2 ratio recomb. 14 whole blood (3) (1) Churchill et al. (1996) (2) Mitchell etal. (1993) (3) Brideau et al. (1996) Cl glucuronidation and sulphatation Scheme 12: Metabolic pathway of diclofenac. Diclofenac Is used mainly as the sodium salt orally or parenterally (75-150 mg/day) and as an ophthalmic solution.
1999). Expression of COX-2 in anglogenesis follows the same route since angiogenesls is important for blood supply and hence the growth of many tumors. , 1999). These findings together with clinical data suggest new options for the use of COX-2 inhibitors In this indication. Aspirin has gained additional importance in the last few years due to its Inhibition of platelet aggregation. , 1987). Additional Effects of COX-inhibitors Some NSAIDs show anti-inflammatory and antiproliferative effects Independent of their COX activity.