title: Potent beta-lactam inhibitors of human cytomegalovirus protease.
abstract: A series of novel monobactam inhibitors of human cytomegalovirus (HCMV) protease has been described that possess a heterocyclic thiomethyl side chain at C-4. Changes to the heterocycle did not significantly change the inhibitory activity of these compounds in an enzymatic assay, although improvements in solubility and cell culture activity were noted. A number of permutations between C-4 substitutions and N-1 derivatives led to the identification of several beta-lactams with antiviral activity in a plaque reduction assay. N-methyl thiotetrazole-containing compounds were found to be the most potent inhibitors in the enzymatic assay.
authors.affiliation: Bio-Méga Research Division, Boehringer Ingelheim (Canada), Laval, Québec. cyoakim@bio-mega.boehringer-ingelheim.ca
authors.forename: C
authors.initials: C
authors.lastname: Yoakim
authors.forename: W W
authors.initials: WW
authors.lastname: Ogilvie
authors.forename: D R
authors.initials: DR
authors.lastname: Cameron
authors.forename: C
authors.initials: C
authors.lastname: Chabot
authors.forename: C
authors.initials: C
authors.lastname: Grand-Maître
authors.forename: I
authors.initials: I
authors.lastname: Guse
authors.forename: B
authors.initials: B
authors.lastname: Haché
authors.forename: S
authors.initials: S
authors.lastname: Kawai
authors.forename: J
authors.initials: J
authors.lastname: Naud
authors.forename: J A
authors.initials: JA
authors.lastname: O'Meara
authors.forename: R
authors.initials: R
authors.lastname: Plante
authors.forename: R
authors.initials: R
authors.lastname: Déziel
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects / Q000201:enzymology*; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D013777:Tetrazoles / Q000138:chemical synthesis / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives; D014764:Viral Proteins / Q000378:metabolism; D047090:beta-Lactams / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D015842:Serine Proteinase Inhibitors; D013777:Tetrazoles; D014764:Viral Proteins; D047090:beta-Lactams; D014508:Urea