3-Hydroxyquinolin-2(1H)-ones As Inhibitors of Influenza A Endonuclease
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- 作者：Hye Yeon Sagong ; Ajit Parhi ; Joseph D. Bauman ; Disha Patel ; R. S. K. Vijayan ; Kalyan Das ; Eddy Arnold ; Edmond J. LaVoie
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：June 13, 2013
- 年：2013
- 卷：4
- 期：6
- 页码：547-550
- 全文大小：283K
- 年卷期：v.4,no.6(June 13, 2013)
- ISSN：1948-5875
文摘
Several 3-hydroxyquinolin-2(1H)-ones derivatives were synthesized and evaluated as inhibitors of 2009 pandemic H1N1 influenza A endonuclease. All five of the monobrominated 3-hydroxyquinolin(1H)-2-ones derivatives were synthesized. Suzuki-coupling of p-fluorophenylboronic acid with each of these brominated derivatives provided the respective p-fluorophenyl 3-hydroxyquinolin(1H)-2-ones. In addition to 3-hydroxyquinolin-2(1H)-one, its 4-methyl, 4-phenyl, 4-methyl-7-(p-fluorophenyl), and 4-phenyl-7-(p-fluorophenyl) derivatives were also synthesized. Comparative studies on their relative activity revealed that both 6- and 7-(p-fluorophenyl)-3-hydroxyquinolin-2(1H)-one are among the more potent inhibitors of H1N1 influenza A endonuclease. An X-ray crystal structure of 7-(p-fluorophenyl)-3-hydroxyquinolin-2(1H)-one complexed to the influenza endonuclease revealed that this molecule chelates to two metal ions at the active site of the enzyme.