Abstract
Several 3-hydroxyquinolin-2(1
H
)-ones derivatives
were synthesized and evaluated as inhibitors of 2009 pandemic H1N1
influenza A endonuclease. All five of the monobrominated 3-hydroxyquinolin(1
H
)-2-ones derivatives were synthesized. Suzuki-coupling
of
p
-fluorophenylboronic acid with each of these
brominated derivatives provided the respective
p
-fluorophenyl
3-hydroxyquinolin(1
H
)-2-ones. In addition to 3-hydroxyquinolin-2(1
H
)-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(1
H
)-one are among the more potent inhibitors of H1N1 influenza
A endonuclease. An X-ray crystal structure of 7-(
p
-fluorophenyl)-3-hydroxyquinolin-2(1
H
)-one complexed
to the influenza endonuclease revealed that this molecule chelates
to two metal ions at the active site of the enzyme.