title: Synthesis, antiviral activity, and biological properties of vinylacetylene analogs of enviroxime.
abstract: A series of vinylacetylene analogs of Enviroxime (1) was synthesized. The new compounds are potent inhibitors of poliovirus in tissue culture. Cross-sensitivity with Enviroxime-derived mutants shows that the new compounds have the same mechanism of action as Enviroxime, which involves the viral 3A protein. In studies with Rhesus monkeys, the p-fluoro derivative 12 was found to be unique in providing oral bioavailability. Metabolism studies using hepatic microsomes suggest that this procedure would be a useful in vitro method for selecting the appropriate animal model for testing oral absorption. Compound 12 was found to be efficacious by oral administration in treating a Coxsackie A21 infection in CD-1 mice.
authors.affiliation: Infectious Diseases Research, Lilly Research Laboratories, Indianapolis, Indiana 46285, USA.
authors.forename: F
authors.initials: F
authors.lastname: Victor
authors.forename: T J
authors.initials: TJ
authors.lastname: Brown
authors.forename: K
authors.initials: K
authors.lastname: Campanale
authors.forename: B A
authors.initials: BA
authors.lastname: Heinz
authors.forename: L A
authors.initials: LA
authors.lastname: Shipley
authors.forename: K S
authors.initials: KS
authors.lastname: Su
authors.forename: J
authors.initials: J
authors.lastname: Tang
authors.forename: L M
authors.initials: LM
authors.lastname: Vance
authors.forename: W A
authors.initials: WA
authors.lastname: Spitzer
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D004770:Enterovirus / Q000187:drug effects; D006801:Humans; D008253:Macaca mulatta; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D010091:Oximes; D017955:Poliovirus / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013449:Sulfonamides
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D010091:Oximes; D013449:Sulfonamides; C021595:viroxime