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.
Original language | English (US) |
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Pages (from-to) | 547-550 |
Number of pages | 4 |
Journal | ACS Medicinal Chemistry Letters |
Volume | 4 |
Issue number | 6 |
DOIs | |
State | Published - Jun 13 2013 |
Externally published | Yes |
Keywords
- 3-hydroxyquinolin-2-ones
- Antiviral
- Endonuclease
- Influenza A
- Quinolinones
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry