title: 3-Hydroxyquinolin-2(1H)-ones As Inhibitors of Influenza A Endonuclease.
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.
authors.affiliation: Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854-8020, United States.
authors.forename: Hye Yeon
authors.initials: HY
authors.lastname: Sagong
authors.affiliation: Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854-8020, United States.
authors.forename: Ajit
authors.initials: A
authors.lastname: Parhi
authors.affiliation: Center for Advanced Biotechnology and Medicine and Department of Chemistry and Chemical Biology, Rutgers University , Piscataway, New Jersey, 08854-5627, United States.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Bauman
authors.affiliation: Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854-8020, United States.
authors.forename: Disha
authors.initials: D
authors.lastname: Patel
authors.affiliation: Center for Advanced Biotechnology and Medicine and Department of Chemistry and Chemical Biology, Rutgers University , Piscataway, New Jersey, 08854-5627, United States.
authors.forename: R S K
authors.initials: RS
authors.lastname: Vijayan
authors.affiliation: Center for Advanced Biotechnology and Medicine and Department of Chemistry and Chemical Biology, Rutgers University , Piscataway, New Jersey, 08854-5627, United States.
authors.forename: Kalyan
authors.initials: K
authors.lastname: Das
authors.affiliation: Center for Advanced Biotechnology and Medicine and Department of Chemistry and Chemical Biology, Rutgers University , Piscataway, New Jersey, 08854-5627, United States.
authors.forename: Eddy
authors.initials: E
authors.lastname: Arnold
authors.affiliation: Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey , Piscataway, New Jersey 08854-8020, United States.
authors.forename: Edmond J
authors.initials: EJ
authors.lastname: LaVoie
keywords: 3-hydroxyquinolin-2-ones; antiviral; endonuclease; influenza A; quinolinones