By by Helmut Buschmann (Editor), Thomas Christoph (Editor), Elmar Friderichs (Editor), Corinna Maul (Ed
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Additional info for Analgesics: From Chemistry and Pharmacology to Clinical Application
Furane, furanone, imidazole, isoxazole, pyrimidine, thiophene, pyrazole, cyclopentenone O — S-NH2 6 R ~S-CH3 • 6 Scheme 3: General structure of carbocycles and heterocycles with vicinal aryl substituents. The structural pre-requisites shown are obligatory for enhanced activity towards COX-2. 2 Cyclooxygenase Inhibition 27 Diaryl- or aryl-heteroaryl-ethers and thioethers HN" F HN^ Ck N02 N02 O' Nimesulid NS-398 0^,0 HNX "~ Flosulid V °st°NH HN H3C V s CH3 F /S. 2 jiM (Laboratoires UPSA) Figure 7.
Hoffmann-La Roche (Rotstein and Sjorgen (Hoffmann-La Roche), 1998) has described aroylnaphthalene derivatives, which exhibit good in vitro activity and selectivity. ). Chugai Seiyaku claimed a series of indoles and diazaindoles, as well as substituted indenes. Interestingly, these compounds lack the alkanoic acid side chain typical of COX Inhibitors (Matsuoka et al. (Chugai Seiyku Kabushiki Kaisha), 1998; 1999). Pfizer (Nakao et al. (Pfizer), 1999; Okumura et al. (Pfizer), 1999) has also reported indole derivatives as selective COX-2 inhibitors.
2 h to > 72 h). In addition, pharmacokinetic studies in rats showed that the clearance of DFP was significantly increased upon multiple dosing. The basis of these pharmacokinetic behaviors was Investigated through in vitro metabolic studies. It was found that DFP was poorly metabolized in human mlcrosomes and hepatocytes, and a low rate of metabolism in vivo probably accounts for the very long half-life. In vivo studies in hepatocytes indicated that DFP induces its own metabolism in the rat, probably through the induction of CYP3A, and this phenomenon was related to the faster clearance of DFP upon multiple dosing.
Analgesics: From Chemistry and Pharmacology to Clinical Application by by Helmut Buschmann (Editor), Thomas Christoph (Editor), Elmar Friderichs (Editor), Corinna Maul (Ed