tetano
Editor, Senior Moderator
ACS Med Chem Lett. 2013 May 7;4(6):547-50. doi: 10.1021/ml4001112. eCollection 2013.
3-Hydroxyquinolin-2(1H)-ones As Inhibitors of Influenza A Endonuclease.
Sagong HY1, Parhi A1, Bauman JD2, Patel D1, Vijayan RS2, Das K2, Arnold E2, LaVoie EJ1.
Author information
Abstract
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.
KEYWORDS:
3-hydroxyquinolin-2-ones; antiviral; endonuclease; influenza A; quinolinones
PMID:
24936242
[PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/24936242
3-Hydroxyquinolin-2(1H)-ones As Inhibitors of Influenza A Endonuclease.
Sagong HY1, Parhi A1, Bauman JD2, Patel D1, Vijayan RS2, Das K2, Arnold E2, LaVoie EJ1.
Author information
Abstract
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.
KEYWORDS:
3-hydroxyquinolin-2-ones; antiviral; endonuclease; influenza A; quinolinones
PMID:
24936242
[PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/24936242