Pyrimido[1,2-b]-1,2,4,5-tetrazin-6-ones as HCMV protease inhibitors: a new class of heterocycles with flavin-like redox properties

Martin J Di Grandi; Kevin J Curran; Ellen Z Baum; Geraldine Bebernitz; George A Ellestad; Wei-Dong Ding; Stanley A Lang; Miriam Rossi; Jonathan D Bloom

doi:10.1016/s0960-894x(03)00789-3

Pyrimido[1,2-b]-1,2,4,5-tetrazin-6-ones as HCMV protease inhibitors: a new class of heterocycles with flavin-like redox properties

Bioorg Med Chem Lett. 2003 Oct 20;13(20):3483-6. doi: 10.1016/s0960-894x(03)00789-3.

Authors

Martin J Di Grandi¹, Kevin J Curran, Ellen Z Baum, Geraldine Bebernitz, George A Ellestad, Wei-Dong Ding, Stanley A Lang, Miriam Rossi, Jonathan D Bloom

Affiliation

¹ Wyeth Research, 401N. Middletown Rd., Pearl River, NY 10965, USA. [email protected]

PMID: 14505653
DOI: 10.1016/s0960-894x(03)00789-3

Abstract

The synthesis and biological activity of pyrimidotetrazin-6-ones against HCMV protease is described. The mechanism of action for these inhibitors is the oxidation of several cysteine residues to generate cross-linked enzyme.

MeSH terms

Cytomegalovirus / enzymology*
Endopeptidases / drug effects*
Endopeptidases / metabolism
Flavins / chemistry*
Oxidation-Reduction
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology*
Pyrimidines / chemistry
Pyrimidines / pharmacology*

Substances

Flavins
Protease Inhibitors
Pyrimidines
Endopeptidases