Diclofenac 4/-methoxy

All compounds of the test dataset are nonsteroidal anti-inflammatory drugs (NSAIDs) and are thus relatively similar in terms of their pharmacological properties (Fig. 18). The compounds are 1, acetylsalicylic acid 2, diclofenac 3, flufe-namic acid 4, flubiprofen 5, ibuprofen 6, indometacin 7, ketoprofen 8, meclofe-namic acid 9, mefenamic acid 10, naproxen 11, piroxicam 12, sulindac sulfide (active metabolite of sulindac) 13, tenoxicam 14, meloxicam 15, cgp 28238 16, DuP-697 17, L-745-337 18, 6-methoxy-2-naphthylacetic acid (active metabolite of nabumeton) 19, NS-389 20, SC 58125. 

Schmitz, G. Lepper, H. Estler, C.-J. High-performance liquid chromatographic method for the routine determination of diclofenac and its hydroxy and methoxy metabolites from in vitro systems. J.Chromatogr., 1993, 620, 158-163 [gradient ced suspensions extracted metabolites LOD 5 ng/mL]... 

O-Methylation of xenobiotic catechols occurs preferentially at the meta position, L-dopa and isoproterenol being classical examples. Frequently 0-methylation is a late event in the metabolism of aryl groups, after they have been oxidized to catechols. Thus the anti-inflammatory drug diclofenac yields in humans 3 -hydroxy-4 -methoxy-diclo-fenac as the major metabolite with a very long plasmatic half-life. Noncatechol diphenols are not subject to methylation, e.g. terbutaUne. A few monophenols can also undergo methylation to a limited extent. 

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