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

Article Details

Citation

Copy to clipboard

Caturla F, Jimenez JM, Godessart N, Amat M, Cardenas A, Soca L, Beleta J, Ryder H, Crespo MI

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

J Med Chem. 2004 Jul 15;47(15):3874-86.

PubMed ID

15239665 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Etoricoxib	Prostaglandin G/H synthase 2	IC 50 (nM)	810	N/A	N/A	Details
Rofecoxib	Prostaglandin G/H synthase 2	IC 50 (nM)	760	N/A	N/A	Details