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.
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).
Dragovich
Peter S
PS
Pfizer Global Research and Development-La Jolla/Agouron Pharmaceuticals, Inc., San Diego, CA 92121-1111, USA. peter.dragovich@pfizer.com
Prins
Thomas J
TJ
Zhou
Ru
R
Johnson
Theodore O
TO
Brown
Edward L
EL
Maldonado
Fausto C
FC
Fuhrman
Shella A
SA
Zalman
Leora S
LS
Patick
Amy K
AK
Matthews
David A
DA
Hou
Xinjun
X
Meador
James W
JW
Ferre
Rose Ann
RA
Worland
Stephen T
ST
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*
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