BETA-LACTAM DERIVATIVES AS INHIBITORS OF HUMAN CYTOMEGALOVIRUS PROTEASE

The development of novel monobactam inhibitors of HCMV protease incorp orating a carbon side chain at C-4 and a urea function at N-1 is descr ibed. Substitution with small groups at the C-3 position of the beta-l actam ring gave an increase in enzymatic activity and in stability; ho wever, a lack of selectivity against other serine proteases was noted. The use of both tri- and tetrasubstituted urea functionalities gave e ffective inhibitors of HCMV protease. Benzyl substitution of the urea moiety was beneficial, especially when strong electron-withdrawing gro ups where attached at the para position. Modest antiviral activity was found in a plaque reduction assay.