title: Evaluation of SQ 34,514: pharmacokinetics and efficacy in experimental herpesvirus infections in mice.
abstract: The new antiviral nucleoside SQ 34,514 [(1R-1 alpha, 2 beta, 3 alpha)-2-amino-9- [2,3-bis(hydroxymethyl)cyclobutyl]-6H-purin-6-one], the active R isomer of racemic SQ 33,054 (cyclobut-G), was evaluated for efficacy in the treatment of herpesvirus infections in mice. SQ 34,514 was orally efficacious in a herpes simplex virus type 1 (HSV-1) systemic infection, an intracerebral HSV-2 infection, a vaginally induced HSV-2 infection in ovariectomized mice, and in a systemic murine cytomegalovirus infection. SQ 34,514 compared favorably with acyclovir and ganciclovir in the treatment of these experimental infections. In mice, SQ 34,514 had an oral bioavailability of 80% based on urinary excretion. SQ 34,514 may have potential value in the therapy of HSV and cytomegalovirus infections in humans.
authors.affiliation: Department of Microbiology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
authors.forename: A
authors.initials: A
authors.lastname: Braitman
authors.forename: M R
authors.initials: MR
authors.lastname: Swerdel
authors.forename: S J
authors.initials: SJ
authors.lastname: Olsen
authors.forename: A V
authors.initials: AV
authors.lastname: Tuomari
authors.forename: J S
authors.initials: JS
authors.lastname: Lynch
authors.forename: B
authors.initials: B
authors.lastname: Blue
authors.forename: T
authors.initials: T
authors.lastname: Michalik
authors.forename: A K
authors.initials: AK
authors.lastname: Field
authors.forename: D P
authors.initials: DP
authors.lastname: Bonner
authors.forename: J M
authors.initials: JM
authors.lastname: Clark
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001927:Brain Diseases / Q000188:drug therapy / Q000382:microbiology; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006561:Herpes Simplex / Q000188:drug therapy*; D051379:Mice; D014627:Vaginitis / Q000188:drug therapy / Q000382:microbiology; D010948:Viral Plaque Assay
chemical_list: D000998:Antiviral Agents; D006147:Guanine; C063638:lobucavir