Design and synthesis of monocyclic β-lactams as mechanism-based inhibitors of human cytomegalovirus protease

Mechanism based inhibitors of HCMV protease have been designed based on the monocyclic β-lactam nucleus, which have been shown to acylate the viral enzyme in a time dependant manner. SAR in a series of monocyclic β-lactam N-ureas, has defined the size and relative stereochemistry of the C-3 substituent producing a low micromolar inhibitor 17b with good aqueous stability and selectivity over the mammalian serine proteases.