Synthesis and Evaluation of Anti-Rhinovirus 1B Activity of Oxazolinyl-Isoflavans and -3(2H)-Isoflavenes

Oxazolinyl-isoflavans and −3(2H)-isoflavenes, substituted or not with a chlorine atom, were synthesized in order to compare their anti-rhinovirus activity with that of previously studied analogous compounds. The activity of the oxazolines and of the esters and acids, which are intermediates in the synthesis, was studied in vitro against rhinovirus serotype 1B infection in HeLa cells. The ability of various non cytotoxic concentrations to interfere with the development of the viral cytopathic effect and plaque formation was examined. All the tested compounds exerted a significant antiviral activity, and most of them were as active as some representative compounds of the oxazolinyl-phenoxyalkylisoxazole (WIN) series. 6-Oxazolinylisoflavan (VI) appeared to be the most interesting compound due to its high activity and therapeutic index. Among the substituted isoflavans and isoflavenes tested so far, the intermediate compound 6-chloro-3 (2H)-isoflavene-4′-carboxylic acid (XIX) was unexpectedly the most potent inhibitor of rhinovirus 1B plaque formation.