Selective chemical inhibition of influenza B virus multiplication.

Analysis of structure-activity relationships in the inhibition of influenza B vir'us multiplication by benzimidazoles has led to the synthesis of new derivatives (Tamm et al., 1956) having 1,000 times the activity of compounds first studied (Tamm et al., 1952; Tamm et al., 1953c). A considerable difference in selectivity of action between 2, 5-dimethylbenzimidazole (MB) and 5, 6 dichloro 1 -/3D ribofuranosylbenzimidazole (DRB) has been established in studies conducted along several lines (Tamm et al., 1954; Tamm and Tyrrell, 1954). To survey the selectivity of action of a large number of benzimidazole derivatives of known virus inhibitory activity and to relate such selectivity to the chemical structure of the compounds, a convenient but quantitative procedure was needed. It was observed that in the presence of certain derivatives at high concentration, the chorioallantoic membranes showed macroscopic evidence of damage on incubation in vitro. The relationship between these changes, reduced oxygen uptake, and microscopic abnormalities has been determined Comparison of benzimidazoles has revealed differences among a number of derivatives in regard to selectivity of action. It will be shown that the relatively low toxicity of the most potent derivatives is specifically related to the presence of the f-D-ribofuranose moiety at NI in the imidazole ring.