A series of vinylacetylene analogs of Enviroxime (1)was synthesized. The new compoundsare potent inhibitors of poliovirus in tissue culture.Cross-sensitivity with Enviroxime-derivedmutants shows that the new compounds have the same mechanism of actionas Enviroxime,which involves the viral 3A protein. In studies with Rhesusmonkeys, the p-fluoro derivative12 was found to be unique in providing oral bioavailability.Metabolism studies using hepaticmicrosomes suggest that this procedure would be a useful invitro method for selecting theappropriate animal model for testing oral absorption. Compound12 was found to be efficaciousby oral administration in treating a Coxsackie A21 infection in CD-1mice.
