4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamides as selective cyclooxygenase-2 inhibitors: enhancement of the selectivity by introduction of a fluorine atom and identification of a potent, highly selective, and orally active COX-2 inhibitor JTE-522(1).
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Hashimoto H, Imamura K, Haruta J, Wakitani K
4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamides as selective cyclooxygenase-2 inhibitors: enhancement of the selectivity by introduction of a fluorine atom and identification of a potent, highly selective, and orally active COX-2 inhibitor JTE-522(1).
J Med Chem. 2002 Mar 28;45(7):1511-7.
- PubMed ID
- 11906292 [ View in PubMed]
- Abstract
A series of 4-(4-cycloalkyl/aryl-oxazol-5-yl)benzenesulfonamide derivatives were synthesized and evaluated for their abilities to inhibit cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) enzymes. In this series, substituent effects at the ortho position to the sulfonamide group on the phenyl ring were examined. Most substituents reduced or lost both COX-2 and COX-1 activities. In contrast, introduction of a fluorine atom preserved COX-2 potency and notably increased COX1/COX-2 selectivity. This work led to the identification of a potent, highly selective, and orally active COX-2 inhibitor JTE-522 [9d, 4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide], which is currently in phase II clinical trials for the treatment of rheumatoid arthritis, osteoarthritis, and acute pain.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Celecoxib Prostaglandin G/H synthase 2 IC 50 (nM) 230 N/A N/A Details Indomethacin Prostaglandin G/H synthase 1 IC 50 (nM) 150 N/A N/A Details Indomethacin Prostaglandin G/H synthase 2 IC 50 (nM) 2380 N/A N/A Details Rofecoxib Prostaglandin G/H synthase 1 IC 50 (nM) 26000 N/A N/A Details Rofecoxib Prostaglandin G/H synthase 2 IC 50 (nM) 340 N/A N/A Details