title: Synthesis and antiviral activity of 6-benzoyl-benzoxazolin-2-one and 6-benzoyl-benzothiazolin-2-one derivatives.
abstract: The synthesis and antiviral activity of an original series of 6-benzoyl-benzoxazolin-2-one and 6-benzoyl-benzothiazolin-2-one derivatives are described. Several compounds were found to have a selective inhibitory activity against human cytomegalovirus (HCMV) and varicella-zoster virus (VZV) in vitro, being inactive against a variety of other DNA and RNA viruses. 6-(3-fluorobenzoyl)benzoxazolin-2-one, 6-(3-fluorobenzoyl)benzothiazolin-2-one, 6-(3-bromobenzoyl)benzothiazolin-2-one, 6-(3-iodobenzoyl)benzothiazolin-2-one, 3-methyl-6-(3-fluorobenzoyl)benzothiazolin-2-one, 3-benzyl-6-benzoyl-benzothiazolin-2-one, 3-benzyl-6-(3-fluorobenzoyl)benzothiazolin-2-one and 3-benzoyl-6-(3-fluorobenzoyl)benzothiazolin-2-one were the most active of the series against HCMV and VZV with a selectivity index (CC50/IC50) ranging from 10 to 20. They displayed similar activity against thymidine kinase competent (TK+) and deficient (TK-) VZV strains, and also proved to be active against clinical HCMV isolates that were resistant to ganciclovir (GCV). Time-of-addition experiments revealed a site of interaction with the HCMV replicative cycle that may be close or similar to that of GCV and cidofovir (HPMPC). The compounds showed poor, if any, activity against herpes simplex virus type 1 (HSV-1) and HSV-2, and were not inhibitory against human immunodeficiency virus and other DNA and RNA viruses. Therefore, these compounds may represent a novel lead for the development of specific HCMV and VZV drugs.
authors.affiliation: Division of Pharmaceutical Chemistry, School of Pharmacy, Université Catholique de Louvain, Brussels, Belgium. Vanderpoorten@bani.ucl.ac.be
authors.forename: K
authors.initials: K
authors.lastname: Van derpoorten
authors.forename: H
authors.initials: H
authors.lastname: Ucar
authors.forename: G
authors.initials: G
authors.lastname: Andrei
authors.forename: R
authors.initials: R
authors.lastname: Snoeck
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: J H
authors.initials: JH
authors.lastname: Poupaert
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003587:Cytomegalovirus / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D014645:Herpesvirus 3, Human / Q000235:genetics; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013055:Spectrophotometry, Infrared
chemical_list: D000998:Antiviral Agents; D001583:Benzoxazoles