Metal mediated protease inhibition: Design and synthesis of inhibitors of the human cytomegalovirus (hCMV) protease

A versatile synthetic route to a novel series of bis-imidazolemethanes desi gned to inhibit the hCMV protease has been developed and a series of potent ial metal binding inhibitors has been identified. In selectivity assays, th e compounds were highly specific for CMV protease and showed no inhibition (IC50 >100 muM) Of Other prototypical serine proteases such as trypsin, ela stase, and chymotrypsin. Although the presence of free zinc ions was found to be an absolute requirement for the in vitro biological activity of this class of inhibitor, the potency of the inhibitors could not be improved bey ond the micromolar level. (C) 2000 Elsevier Science Ltd. All rights reserve d.