Antirhino/Enteroviral Vinylacetylene Benzimidazoles: A Study of Their Activity and Oral Plasma Levels in Mice

In an effort to find an orally bioavailable antiviral for the treatment of rhino/enteroviral infections, a series of vinylacetylene benzimidazoles (11a−o, 12, and 18a) was made. Initial studies of this class of antivirals showed that fluorine substitution on the left-hand phenyl ring in combination with the vinylacetylene moiety gave the requisite mix of physical properties to achieve good in vitro antiviral activity as well as respectable oral bioavailability in rhesus monkeys. To ascertain the generality of this finding and to broaden the scope of the structure−activity relationship (SAR), the present study concentrated on fluoro substitution of this class of molecules. The initial antiviral activity for each analogue was measured using human rhinovirus 14 (HRV-14). This served as an indicator of general antiviral activity for SAR purposes. Subsequently, the spectrum of antirhino/enteroviral activity of the more interesting analogues was evaluated through testing against a panel of seven additional rhin...