Novel Azolylalkyloxy Compounds with Antipicornaviral Activity

A novel series of azolylalkyloxy compounds was designed, synthesized and evaluated for antipicornaviral activity. Several of the compounds exhibited in vitro activity comparable to that of Disoxaril. An investigation of qualitative structure-activity relationships indicated that the optimal length of the alkyl chain is six or seven carbon atoms, with seven being marginally superior. The effect of different azole moieties on activity was relatively small, with 3-methylisoxazole and 4-methylthiazole being most effective. The nature of the oxy substituent was found to be extremely important for antipicornaviral activity. The 2-dibenzofuryl group proved to be the most effective oxy substituent for this class of compounds. Compounds 11 and 22, combining dibenzofuran with 3-methylisoxazole and 4-methylthiazole, respectively, were highly effective in vitro against a wide range of human rhinoviruses as well as several enteroviruses.