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β-Lactam Derivatives as Inhibitors of Human Cytomegalovirus Protease

1998; American Chemical Society; Volume: 41; Issue: 15 Linguagem: Inglês

10.1021/jm980131z

1520-4804

Christiane Yoakim, William W. Ogilvie, Dale R. Cameron, Catherine Chabot, Ingrid Guse, Bruno Haché, Julie Naud, Jeff A. O’Meara, Raymond Plante, Robert Déziel,

Synthesis and Catalytic Reactions

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