4‑Iminooxazolidin-2-one as a Bioisostere of the Cyanohydrin Moiety: Inhibitors of Enterovirus 71 3C Protease

A recently
reported potent inhibitor of enterovirus 71 3C protease,
(R)-1, was found to have stability and
potential toxicity issues due to the presence of a cyanohydrin moiety.
Modifying the labile cyanohydrin moiety, by serendipity, led to the
discovery of 4-iminooxazolidin-2-one-based inhibitors 4e and 4g with potent inhibitory activity and significantly
improved stability. In vivo pharmacokinetic studies of 4e also demonstrated high plasma exposure and moderate half-life. These
compounds have shown potential of becoming anti-EV71 drug candidates.