Arylketotetramethylene analogues of disoxaril with anti-human rhinovirus 14 activity

Arylketotetramethylene analogues of disoxaril (WIN 51711) were synthesized by reaction of 1-aryl-5-chloropentan-1-ones with 2-(4-hydroxyphenyl)-4,5-dihydro oxazoles, ethyl 4-hydroxybenzoates and 4-hydroxybenzonitrile. The new derivatives were tested for antiviral activity against various human rhinovirus (HRV) serotypes. The best activity was exhibited by the ethoxycarbonyl derivatives, whereas the oxazoline counterparts were less active and the cyano derivatives totally inactive. 5-[4-(4,5-Dihydro-2-oxazolyl)phenoxy]-1-(4-methoxyphenyl)pentan-1-one and ethyl 4-[5-(4-methylthiophenyl)-5-oxopentoxy] benzoate were more active than, and as active as, disoxaril, respectively, against HRV-14. Moreover, they were 10 times less cytotoxic.