PMID: 11906292Mar 22, 2002Paper

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)

Journal of Medicinal Chemistry
Hiromasa HashimotoKorekiyo Wakitani

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.

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Citations

Aug 2, 2005·Journal of Computer-aided Molecular Design·Hwangseo Park, Sangyoub Lee
Dec 4, 2003·Bioorganic & Medicinal Chemistry·Wenhui HuGuifang Cheng
Mar 19, 2004·Bioorganic & Medicinal Chemistry·Hye-Jung KimSung-Eun Yoo
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Mar 18, 2004·Bioorganic & Medicinal Chemistry Letters·Joo Hyun MohShin Chung
Feb 5, 2003·Bioorganic & Medicinal Chemistry Letters·Yung Hyup HyupShin Chung
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Feb 29, 2008·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ermitas AlcaldeSantiago García-Granda
Sep 8, 2018·Chemical Communications : Chem Comm·Beibei Luo, Zhiqiang Weng
Oct 3, 2018·SAR and QSAR in Environmental Research·Y XiA Yan
Oct 17, 2018·Future Medicinal Chemistry·Priyanka ChandelRupinder Kaur
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Dec 25, 2009·Journal of Enzyme Inhibition and Medicinal Chemistry·Seref DemirayakRana Aslan
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