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Synfacts 2006(6): 0532-0532  
DOI: 10.1055/s-2006-934491
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of an NO-Releasing Prodrug of Rofecoxib

Contributor(s): Philip Kocienski
F. C. Engelhardt*, Y.-J. Shi, C. J. Cowden, D. A. Conlon, B. Pipik, G. Zhou, J. M. McNamara, U.-H. Dolling
Merck & Company, Inc., Rahway, USA
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Publication History

Publication Date:
19 May 2006 (online)

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Significance

CINODS (COX-inhibiting nitric oxide donors) are a new class of antiinflammatory drug that minimizes gastrointestinal injury through the release of nitric oxide. The CINOD target shown above is designed to transform in vivo to Rofecoxib (VIOXX), hexane-1,6-diol and nitric oxide. The key step in the synthesis is the stereo- and regioselective carbometallation of propargyl alcohol A to give the tetrasubstituted alkene C via carboxylation of the adduct B.