Abstract
A panel of four isomeric acetylfuran analogues of disoxaril were prepared. Using a 96-well tissue culture inhibitory dose assay (TCID), these acetylfuran isomers were screened against 15 rhinovirus serotypes. Comparison of the results obtained suggested that antiviral activity was related to hydrogen bond participation by the carbonyl oxygen within the viral pocket. Modelling acetylfuran conformations using an X-ray crystal structure template of 1 in HRV-14 demonstrates that three of the four isomers can adopt the desired conformation for this hydrogen bonding, and the fourth isomer 15 is prohibited by steric constraints from achieving the necessary conformation. These observations are consistent with the hypothesis that broad-spectrum antirhinoviral activity may require a hydrogen bond acceptor at that region of the inhibitor.