Synthesis and biological evaluation of 3,4-diaryloxazolones: A new class of orally active cyclooxygenase-2 inhibitors.

Article Details

Citation
Copy to clipboard

Puig C, Crespo MI, Godessart N, Feixas J, Ibarzo J, Jimenez JM, Soca L, Cardelus I, Heredia A, Miralpeix M, Puig J, Beleta J, Huerta JM, Lopez M, Segarra V, Ryder H, Palacios JM

Synthesis and biological evaluation of 3,4-diaryloxazolones: A new class of orally active cyclooxygenase-2 inhibitors.

J Med Chem. 2000 Jan 27;43(2):214-23.

PubMed ID
10649977 [ View in PubMed
]
Abstract

A series of 3,4-diaryloxazolones 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. The replacement of the methyl sulfone group on the 4-phenyl ring by a sulfonamide moiety resulted in compounds with superior in vivo antiinflammatory properties. In the sulfonamide series, the introduction of a methyl group at the 5-position of the oxazolone ring gave rise to very COX-2-selective compounds but with decreased in vivo activity. Selected 3,4-diaryloxazolones exhibited excellent activities in experimental models of arthritis and hyperalgesia. The in vivo activity of these compounds was confirmed with the evaluation of their antipyretic effectiveness and their ability to inhibit migration of proinflammatory cells. As expected from their COX-2 selectivity, most of the active compounds lacked gastrointestinal toxicity in vivo in rats after a 4-day treatment of 100 mg/kg/day. Within this novel series, sulfonamides 9-11 have been selected for further preclinical evaluation.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
CelecoxibProstaglandin G/H synthase 2IC 50 (nM)1100N/AN/ADetails
IndomethacinProstaglandin G/H synthase 1IC 50 (nM)250N/AN/ADetails
IndomethacinProstaglandin G/H synthase 2IC 50 (nM)220N/AN/ADetails
NaproxenProstaglandin G/H synthase 1IC 50 (nM)11000N/AN/ADetails
NaproxenProstaglandin G/H synthase 2IC 50 (nM)18900N/AN/ADetails