Enterovirus 71 (EV71) caused a large outbreak in Taiwan in 1998 with 78 deaths, and smaller outbreaks recurred in 2000 and 2001. Virologic and pathologic studies indicated that EV71 was the most important agent related to severe and fatal cases and that a neurogenic inflammatory response was involved in the pathogenesis of cardiopulmonary collapse resulting from fulminant EV71 infection. A series of novel, oxime ether-containing pyridyl imidazolidinones, was synthesized and possessed capsid-binding activity to inhibit viral attachment and/or virus uncoating. It is very interesting that this class of compounds is specific for human enteroviruses, in particular, EV71. The studies of SAR revealed that the chain length of the alkyl linker and alkyl substituent at the oxime ether group great influenced the antienterovirus activity in vitro. The introduction of methyl group on the alkyl linker led to increase activity against EV71 compared with that of the corresponding compound. The pyridyl imidazolidinone with an ethyl oxime ether group located at the para position of the phenoxyl ring was identified as the most potent EV71 inhibitor. Furthermore, the ethyl oxime ether derivative has been shown broad-spectrum activity against most of the serotypes of enteroviruses and possessed a good oral bioavailability.?
