Open AccessPotent β-Lactam Inhibitors of Human Cytomegalovirus Protease
Author(s) -
Christiane Yoakim,
William W. Ogilvie,
Dale R. Cameron,
Catherine Chabot,
Chantal GrandMaître,
Ingrid Guse,
Bruno Haché,
Stephen H. Kawai,
Julie Naud,
Jeff A. O’Meara,
Raymond Plante,
Robert Déziel
Publication year - 1998
Publication title -
antiviral chemistry and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.919
H-Index - 51
eISSN - 2040-2066
pISSN - 0956-3202
DOI - 10.1177/095632029800900502
Subject(s) - human cytomegalovirus , enzyme , protease , enzyme inhibitor , chemistry , lactam , biochemistry , biological activity , in vitro , stereochemistry , gene
A series of novel monobactam inhibitors of human cytomegalovirus (HCMV) protease has been described that possess a heterocyclic thiomethyl side chain at C-4. Changes to the heterocycle did not significantly change the inhibitory activity of these compounds in an enzymatic assay, although improvements in solubility and cell culture activity were noted. A number of permutations between C-4 substitutions and N-1 derivatives led to the identification of several β-lactams with antiviral activity in a plaque reduction assay. N-methyl thiotetrazole-containing compounds were found to be the most potent inhibitors in the enzymatic assay.