Synthesis and Antiviral Activity of Dimeric Capsid-Binding Inhibitors of Human Rhinovirus (HRV)

A set of dimeric analogues of known rhinovirus capsid-binders Pleconaril 1 and Pirodavir 55 has been synthesized and tested against two representative human rhinovirus (HRV) strains. Dimers with linker lengths ranging from five atoms up to approximately 60 atoms were prepared by coupling various functionalized monomeric precursors. Many of the dimers showed activity against HRV, with the most active compounds being those with the shorter linking groups. The lower activity of all the dimers relative to similar monomeric compounds, and especially the low activity of the longest dimers, suggests that cooperative bivalent binding is not occurring with any of these compounds.