Raymond Plante

Potent β-Lactam Inhibitors of Human Cytomegalovirus Protease:

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.

A simple synthesis of γ and δ-keto α-amino acid derivatives

Abstract The γ and δ-keto α-amino acid derivatives 1a and 1b were prepared from L-aspartic and L-glutamic acid respectively via alkylation of the corresponding β-ketoesters 3a and 3b followed by subsequent ester cleavage and decarboxylation.

Herpes simplex virus ribonucleotide reductase subunit association inhibitors: the effect and conformation of β-alkylated aspartic acid derivatives

Incorporating beta-alkylated aspartic acid derivatives into herpes simplex virus ribonucleotide reductase subunit association inhibitors can improve inhibitor potency up to 50 times over the corresponding inhibitors containing an unsubstituted aspartic acid. A combination of NMR studies, conformational analysis, and molecular mechanics calculations suggests that the beta-alkyl group improves inhibitor potency by favoring the bioactive conformation of the critical aspartic acid carboxyl group. Further support for this hypothesis is provided by a potent conformationally restricted aspartic acid derivative in which the carboxyl group is locked in the putative bioactive conformation.