ACETYLFURANS AS BIO-ISOSTERES FOR 3-METHYLISOXAZOLE - THE EFFECT OF ACETYLFURAN POSITIONAL ISOMERS ON ANTIRHINOVIRAL ACTIVITY

A panel of four isomeric acetylfuran analogues of disoxaril were prepa red, Using a 96-well tissue culture inhibitory dose assay (TCID), thes e acetylfuran isomers were screened against 15 rhinovirus serotypes. C omparison of the results obtained suggested that antiviral activity wa s 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 t he four isomers can adopt the desired conformation for this hydrogen b onding, and the fourth isomer 15 is prohibited by steric constraints f rom achieving the necessary conformation. These observations are consi stent with the hypothesis that broad-spectrum antirhinoviral activity may require a hydrogen bond acceptor at that region of the inhibitor.