Facile air oxidation of the conjugate base of rofecoxib (Vioxx™), a possible contributor to chronic human toxicity
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2020, Bioorganic ChemistryCitation Excerpt :However, the risk of these effects may be a result of complex interplay among a specific drug molecule, dose and CV risk factors [4]. Rofecoxib was withdrawn from the market due to its associated CV risk that may be mediated by a maleic anhydride metabolite [5]. Rofecoxib was shown to have a much higher risk compared with celecoxib [6].
Synthesis and Biological Activities of Vicinal Diaryl Furans
2018, Vicinal Diaryl Substituted Heterocycles: A Gold Mine for the Discovery of Novel Therapeutic AgentsStereoselective synthesis and anti-proliferative effects on prostate cancer evaluation of 5-substituted-3,4-diphenylfuran-2-ones
2013, European Journal of Medicinal ChemistryCitation Excerpt :Now, a novel series of rofecoxib derivatives, possessing a central furan-2-one ring are shown as selective COX-2 inhibitors, which exhibits good anti-proliferative effects on prostate cancer activity profiles. Diarylheterocycles, and other central ring pharmacophore templates, have been extensively studied as cyclooxygenase inhibitors [24] (Fig. 1). SAR studies have shown that for optimum COX-2 selectivity and inhibitory potency, a SO2Me or SO2NH2 substituent at the para-position of a phenyl ring, and that the presence of a p-F substituent on the nonsulfonyl vicinal phenyl ring improved the in vivo activity [25,26].
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2009, Trends in Pharmacological Sciences2,3,5-Substituted tetrahydrofurans: COX-2 inhibitory activities of 5-hydroxymethyl-/carboxyl-2,3-diaryl-tetrahydro-furan-3-ols
2008, European Journal of Medicinal ChemistryCitation Excerpt :Out of the 10 compounds for which the results are presented here, compounds 16–18 and 20 exhibit considerable inhibition of COX-2 which is better than the COX-2 inhibitory activity of celecoxib and comparable to that of rofecoxib. However, the reluctance of these molecules to air oxidation provides an advantage over rofecoxib which has been demonstrated to show toxicity due to its oxidation to maleic anhydride derivative [33]. Significant anti-cancer activities of compounds 15–19 have been observed at some specific cell lines of 59 human tumor cell line panels [34].
Are COX-2 inhibitors preferable to non-selective non-steroidal anti-inflammatory drugs in patients with risk of cardiovascular events taking low-dose aspirin?
2007, LancetCitation Excerpt :By comparison, in two studies in patients with known coronary artery disease, administration of rofecoxib for 2–6 months was not associated with changes in flow-mediated dilatation.95,96 Rofecoxib and celecoxib show different effects on cell-membrane integrity, which could explain the differing cardiovascular safety profiles for these drugs.97,98 Radiographical diffraction analyses suggest that rofecoxib changes the structure of cell-surface lipid molecules, thereby promoting oxidation of low-density lipoproteins and reducing the antioxidant capacity of plasma.