The discovery that 4-[3-ethyl-6-[(3,4-methylenedioxy)phenyl]-3-hexenyl]-3,5-heptanedione (40) exhibited an in vitro inhibitory effect against equine rhinovirus led to a structure--activity study to establish the criteria for optimum activity. Modification of the bridge included removal of the ethyl group and reduction of the double bond. The heptanedione was replaced with hexanedione and pentanedione with a minimal effect. The effect of replacing the heptanedione with beta-keto esters and monoketones was also investigated. Maintaining the hexamethylene bridge and heptanedione, the methylenedioxy group was replaced with various substitutents. In general, most substituents did not adversely affect activity particularly against equine rhinovirus although there was some variation in activity against herpesvirus. Strongly hydrophilic groups significantly reduced activity. Finally, the effect of varying the length of the alkyl bridge was examined in the 4-hydroxyphenyl series, where peak activity was attained with n = 8.