title: Synthesis and antiviral activity of monobactams inhibiting the human cytomegalovirus protease.
abstract: A series of monobactam inhibitors of HCMV (N(o)) protease bearing a heterocycle linked by a methylene group at C-4 is described. Inhibitors containing a heterocycle such as a 2-furyl, 2-thiophenyl, 4-methyl-2-tetrazole and 2-benzothiazole were found to be active in a plaque reduction assay. Furthermore, 2-benzothiazole derivatives were shown to inhibit the HCMV protease activity inside cells by using a cell transfection assay, indicating that their antiviral activity in the plaque reduction assay could be attributed to protease inhibition.
authors.affiliation: Boehringer Ingelheim (Canada) Ltd., Bio-Méga Research Division, Laval, Québec, Canada. wogilvie@bio-mega.boehringer-ingelheim.ca
authors.forename: W W
authors.initials: WW
authors.lastname: Ogilvie
authors.forename: C
authors.initials: C
authors.lastname: Yoakim
authors.forename: F
authors.initials: F
authors.lastname: Dô
authors.forename: B
authors.initials: B
authors.lastname: Haché
authors.forename: L
authors.initials: L
authors.lastname: Lagacé
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: Déziel
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019556:COS Cells; D003587:Cytomegalovirus / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D008997:Monobactams / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000187:drug effects*; D013057:Spectrum Analysis; D010948:Viral Plaque Assay
chemical_list: D000998:Antiviral Agents; D008997:Monobactams; D011480:Protease Inhibitors; D012697:Serine Endopeptidases; C071910:assemblin