Synthesis and antiviral activity of monobactams inhibiting the human cytomegalovirus protease.
A series of monobactam inhibitors of HCMV (N(o)) protease bearing a heterocycle linked by a methylene group at C-4 is described. Inhibitors containing a heterocycle such as a 2-furyl, 2-thiophenyl, 4-methyl-2-tetrazole and 2-benzothiazole were found to be active in a plaque reduction assay. Furthermore, 2-benzothiazole derivatives were shown to inhibit the HCMV protease activity inside cells by using a cell transfection assay, indicating that their antiviral activity in the plaque reduction assay could be attributed to protease inhibition.
Ogilvie
W W
WW
Boehringer Ingelheim (Canada) Ltd., Bio-Méga Research Division, Laval, Québec, Canada. wogilvie@bio-mega.boehringer-ingelheim.ca
Yoakim
C
C
Dô
F
F
Haché
B
B
Lagacé
L
L
Naud
J
J
O'Meara
J A
JA
Déziel
R
R
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019556:COS Cells; D003587:Cytomegalovirus / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D008997:Monobactams / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000187:drug effects*; D013057:Spectrum Analysis; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D008997:Monobactams; D011480:Protease Inhibitors; D012697:Serine Endopeptidases; C071910:assemblin