title: Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. Part 7: structure-activity studies of bicyclic 2-pyridone-containing peptidomimetics.
abstract: The structure-based design, chemical synthesis, and biological evaluation of bicyclic 2-pyridone-containing human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. An optimized compound is shown to exhibit antiviral activity when tested against a variety of HRV serotypes (EC(50)'s ranging from 0.037 to 0.162 microM).
authors.affiliation: Pfizer Global Research and Development-La Jolla/Agouron Pharmaceuticals, Inc., San Diego, CA 92121-1111, USA. peter.dragovich@pfizer.com
authors.forename: Peter S
authors.initials: PS
authors.lastname: Dragovich
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Prins
authors.forename: Ru
authors.initials: R
authors.lastname: Zhou
authors.forename: Theodore O
authors.initials: TO
authors.lastname: Johnson
authors.forename: Edward L
authors.initials: EL
authors.lastname: Brown
authors.forename: Fausto C
authors.initials: FC
authors.lastname: Maldonado
authors.forename: Shella A
authors.initials: SA
authors.lastname: Fuhrman
authors.forename: Leora S
authors.initials: LS
authors.lastname: Zalman
authors.forename: Amy K
authors.initials: AK
authors.lastname: Patick
authors.forename: David A
authors.initials: DA
authors.lastname: Matthews
authors.forename: Xinjun
authors.initials: X
authors.lastname: Hou
authors.forename: James W
authors.initials: JW
authors.lastname: Meador
authors.forename: Rose Ann
authors.initials: RA
authors.lastname: Ferre
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Worland
mesh_terms: D000086042:3C Viral Proteases; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D018716:Molecular Mimicry; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012229:Rhinovirus / Q000187:drug effects / Q000201:enzymology*; D012703:Serotyping; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000037:antagonists & inhibitors*
chemical_list: D000998:Antiviral Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015853:Cysteine Proteinase Inhibitors; D011728:Pyridones; D014764:Viral Proteins; C017679:2-hydroxypyridine; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases