Synthesis and Biological Evaluation of 2-Phenylpyran-4-ones: A New Class of Orally Active Cyclooxygenase-2 Inhibitors
Citations Over TimeTop 13% of 2004 papers
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.
Related Papers
- → Design and synthesis of sulfonyl-substituted 4,5-diarylthiazoles as selective cyclooxygenase-2 inhibitors(1999)34 cited
- → 2,3-Diarylbenzopyran derivatives as a novel class of selective cyclooxygenase-2 inhibitors(2003)65 cited
- → Diastereoselective synthesis of mixanpril, an orally active dual inhibitor of neutral endopeptidase and angiotensin converting enzyme(1995)17 cited
- → 3,4-diarylpyrazoles: Potent and selective inhibitors of cyclooxygenase-2(1997)16 cited
- → Conversion of cyclooxygenase inhibitors into hydroxythiazole 5-lipoxygenase inhibitors(1997)7 cited