Synthesis and biological evaluation of 2,3-diarylpyrazines and quinoxalines as selective COX-2 inhibitors

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• 作者：Singh ; Sunil K. ; Saibaba ; V. ; Ravikumar ; V. ; Rudrawar ; Santosh V. ; Daga ; Pankaj ; Rao ; C. Seshagiri ; et. al.
• 关键词：2 ; 3-Diarylpyrazines ; 2 ; 3-Diarylquinoxalines ; COX-2 inhibitors
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2004
• 出版时间：April 15, 2004
• 年：2004
• 卷：12
• 期：8
• 页码：1881-1893
• 全文大小：434 K

文摘

Several 2,3-diaryl pyrazines and quinoxalines with 4-sulfamoyl (SO₂NH₂)/methylsulfonyl (SO₂Me)-phenyl pharmacophores have been synthesized and evaluated for the cyclooxygenase (COX-1/COX-2) inhibitory activity. Smaller groups such as methoxy, methyl and fluoro when substituted at/around position-4 of the adjacent phenyl ring, have great impact on the selective COX-2 inhibitory activity of the series. Many potential compounds were obtained from a brief structure–activity relationship (SAR) study. Two of these, compounds 11 and 25 exhibited excellent in vivo activity in the established animal model of inflammation. Since compound 25 possessed an amenable sulfonamide group, two of its prodrugs 48 and 49 were also synthesized. Both of them have excellent in vivo potential, and represent a new class of COX-2 inhibitor.