title: Design and synthesis of irreversible depsipeptidyl human rhinovirus 3C protease inhibitors.
abstract: Novel tripeptidyl C-terminal Michael acceptors with an ester replacement of the P(2)-P(3) amide bond were investigated as irreversible inhibitors of the human rhinovirus (HRV) 3C protease (3CP). When screened against HRV serotype-14 the best compound was shown to have very good 3CP inhibition (k(obs)/[I]=270,000M(-1)s(-1)) and potent in vitro antiviral activity (EC(50)=7.0nM).
authors.affiliation: Pfizer Global Research and Development, La Jolla, 3565 General Atomics Court, San Diego, CA 92121, USA. swebber@anadyspharma.com
authors.forename: S E
authors.initials: SE
authors.lastname: Webber
authors.forename: J T
authors.initials: JT
authors.lastname: Marakovits
authors.forename: P S
authors.initials: PS
authors.lastname: Dragovich
authors.forename: T J
authors.initials: TJ
authors.lastname: Prins
authors.forename: R
authors.initials: R
authors.lastname: Zhou
authors.forename: S A
authors.initials: SA
authors.lastname: Fuhrman
authors.forename: A K
authors.initials: AK
authors.lastname: Patick
authors.forename: D A
authors.initials: DA
authors.lastname: Matthews
authors.forename: C A
authors.initials: CA
authors.lastname: Lee
authors.forename: B
authors.initials: B
authors.lastname: Srinivasan
authors.forename: T
authors.initials: T
authors.lastname: Moran
authors.forename: C E
authors.initials: CE
authors.lastname: Ford
authors.forename: M A
authors.initials: MA
authors.lastname: Brothers
authors.forename: J E
authors.initials: JE
authors.lastname: Harr
authors.forename: J W
authors.initials: JW
authors.lastname: Meador
authors.forename: R A
authors.initials: RA
authors.lastname: Ferre
authors.forename: S T
authors.initials: ST
authors.lastname: Worland
mesh_terms: D000086042:3C Viral Proteases; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012229:Rhinovirus / Q000187:drug effects; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D010455:Peptides; D011480:Protease Inhibitors; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases