SYNTHESIS, ANTIVIRAL ACTIVITY, AND BIOLOGICAL PROPERTIES OF VINYLACETYLENE ANALOGS OF ENVIROXIME

A series of vinylacetylene analogs of Enviroxime (1) was synthesized. The new compounds are potent inhibitors of poliovirus in tissue cultur e. Cross-sensitivity with Enviroxime-derived mutants shows that the ne w compounds have the same mechanism of action as Enviroxime, which inv olves the viral 3A protein. In studies with Rhesus monkeys, the p-fluo ro derivative 12 was found to be unique in providing oral bioavailabil ity. Metabolism studies using hepatic microsomes suggest that this pro cedure 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 infect ion in CD-1 mice.