Synthesis and biological evaluation of 2-phenylpyran-4-ones: a new class of orally active cyclooxygenase-2 inhibitors

Journal of Medicinal Chemistry
Francisco CaturlaMaría I Crespo

Abstract

A series of 2-phenylpyran-4-ones were prepared and evaluated for their ability to inhibit cyclooxygenase-2 (COX-2). Extensive structure-activity relationship work was carried out within this series, and a number of potent and selective COX-2 inhibitors were identified. Compounds having a p-methylsulfone group at the 2-phenyl ring showed the best COX-2 inhibitory activity. The introduction of a substituted phenoxy ring at position 3 enhanced both the in vitro and in vivo activity within the series. A selected group of 3-phenoxypyran-4-ones exhibited excellent activity in an experimental model of pyresis. The in vivo antiinflammatory activity of these compounds was confirmed with the evaluation of their antiarthritic and analgesic effectiveness. Moreover, their pharmacokinetic profile in rats is compatible with a once a day administration by oral route in humans. Within this novel series, compounds 21, 31, 34, and 35 have been selected for further preclinical and clinical evaluation.

References

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Dec 11, 2002·The Journal of Surgical Research·Balraj Singh, Anthony Lucci
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Feb 19, 2003·Journal of Pain and Symptom Management·Lowell W ReynoldsKenneth M Verburg

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Citations

May 2, 2006·Bioorganic & Medicinal Chemistry Letters·Francisco CaturlaGraham Warrellow
Jan 8, 2005·Stroke; a Journal of Cerebral Circulation·Costantino Iadecola, Philip B Gorelick
Oct 3, 2018·SAR and QSAR in Environmental Research·Y XiA Yan
Feb 15, 2019·Journal of Chemical Information and Modeling·Zijian QinAixia Yan

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