Selective Inhibitors of Cyclooxygenase-2 COX

Talley, J. J. Selective Inhibitors of Cyclooxygenase-2 (COX-2). Progress in Medicinal Chemistry - Vol. 

Talley JJ (1999) Selective inhibitors of cyclooxygenase-2 (COX-2). Prog Med Chem 36, 201-234. 

The efficacy and safety of cyclooxygenase-2 (COX-2) selective inhibitors (e.g., celecoxib) have not been fully assessed in gouty arthritis, but they are more costly than conventional NSAIDs and are unlikely to result in fewer GI complications because of the short duration of therapy. 

Kalgutkar, A. S., Crews, B. C., Rowlinson, S. W., Marnett, A. B., Kozak, K. R., Remmel, R. P., Marnett, L. J. Biochemically based design of cyclooxygenase-2 (COX-2) inhibitors facile conversion of nonsteroidal antiinflammatory drugs to potent and highly selective COX-2 inhibitors, Proc. Natl. Acad. Sci. USA 2000, 97, 925-930. 

Celecoxib is a selective COX-2 inhibitor/GI agent that reduces inflammation (e.g., pain, redness, swelling, heat), fever, and pain by inhibiting chemicals in the body that cause inflammation, fever, and pain. This is probably caused by the inhibition of prostaglandin synthesis, primarily via inhibition of cyclooxygenase-2 (COX-2) isoenzyme. Celecoxib is indicated in relief of symptoms of osteoarthritis relief of symptoms of rheumatoid arthritis in adults management of acute pain in adults treatment of primary dysmenorrhea and reduction of the number of adenomatous colorectal polyps in familial adenomatous polyposis (FAP), as an adjunct to usual care (e.g., endoscopic surveillance, surgery). 

Selective cyclooxygenase-2 (COX-2) inhibitors have not been shown to be any more effective than the combination of a PPI... 

Cyclooxygenase-2 (COX-2)-selective inhibitors produce results comparable with those of traditional NSAIDs. However, cardiovascular safety concerns and the high cost of COX-2 inhibitors argue against their use for this disorder. 

Compound 330 (Figure 31) is a potent and very selective cyclooxygenase-2 (COX-2) inhibitor <1997BMCL57>. Three-dimensional quantity-structure activity relationship (3-D QSAR) analysis of this compound and other members of a series of 5,6-diarylthiazolo[3,2-A][l,2,4]triazoles has been carried out <2004MI5>. 

While comparatively few dihydrodiols have been observed in the metabolism of phenyl-containing drugs, the examples above are far from unique. Thus, oxazepam incubated in rat, mouse, and human microsomes did yield a dihydrodiol besides the para-phenol [82], A more-recent example is that of rofecoxib (10.22), a potent and selective cyclooxygenase-2 (COX-2) inhibitor. In rats and dogs, phenyl oxidation produced 4 -hydroxyrofecoxib and rof-ecoxib-3, 4 -dihydrodiol as urinary metabolites of intermediate quantitative importance [83]. 

Most of the drugs that inhibit cyclooxygenase do inhibit both Cox-1 and Cox-2 this applies to drugs such as diclofenac, indomethacine, and acetylsalicylic acid. More recent developments have led to selective inhibitors of Cox-... 

One class of modem drugs is well known to induce a shift from the type-1 to a type-2 dominated immune response the selective cyclooxygenase-2 (COX-2) inhibitors. Several studies demonsh ated the type-2 inducing effect of PGE2— the major product of COX-2— w hile inhibition of COX-2 is accompanied by inhibition of type-2 cytokines and induction of type-1 cytokines (Pyeon et al., 2000 Stolina et al., 2000). Recendy, PGE2 has been shown to enhance the production of... 

Boyer D, Bauman JN, Walker DP, et al. Utility of MetaSite in improving metabolic stability of the neutral indomethacin amide derivative and selective cyclooxygenase-2 (COX-2) inhibitor 2-(l-(4-chlorobenzoyl)-5-methoxy-2-methyl-lf/-indol-3-yl]-N-phenethyl-acetamide. Drug Metab Dispos. 2009 37(5) 999-1008. 

Standard dosages of a proton pump inhibitor and a non-selective NSAID appear to be as effective as a selective cyclooxygenase-2 (COX-2) inhibitor in reducing the risk of NSAID-induced ulcers and upper Cl complications. 

Nonsteroidal anti-inflammatory drugs (NSAIDs) Standard dosage regimens of aspirin or traditional NSAIDs (e.g., ibuprofen) selective cyclooxygenase-2 (COX-2) inhibitors should be used in patients at risk for upper Gl bleeding use with caution in renal insufficiency... 

NSAIDs are associated with Gl, renal, liver, or central nervous system toxicity. Appropriate monitoring with complete blood count, serum creatinine, and hepatic transaminase levels is valuable in detecting potential toxicity. Cyclooxygenase-2 (COX-2)-specific inhibitors carry a lower risk of Gl bleeding or platelet inhibition, and may be appropriate in selected patients. 

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