Inhibition of human cytomegalovirus protease by enedione derivatives of thieno[2,3-d]oxazinones through a novel dual acylation/alkylation mechanism

I L Pinto; R L Jarvest; B Clarke; C E Dabrowski; A Fenwick; M M Gorczyca; L J Jennings; P Lavery; E J Sternberg; D G Tew; A West

doi:10.1016/s0960-894x(99)00005-0

Inhibition of human cytomegalovirus protease by enedione derivatives of thieno[2,3-d]oxazinones through a novel dual acylation/alkylation mechanism

Bioorg Med Chem Lett. 1999 Feb 8;9(3):449-52. doi: 10.1016/s0960-894x(99)00005-0.

Authors

I L Pinto¹, R L Jarvest, B Clarke, C E Dabrowski, A Fenwick, M M Gorczyca, L J Jennings, P Lavery, E J Sternberg, D G Tew, A West

Affiliation

¹ SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK. Ivan_Pinto-1@sbphrd.com

PMID: 10091700
DOI: 10.1016/s0960-894x(99)00005-0

Abstract

Enedione derivatives of thieno[2,3-d]oxazinones are nanomolar inhibitors of CMV protease which act through a novel dual acylation of the catalytic serine and alkylation of the protease cysteine 161 via a Michael addition to the enedione moiety of the inhibitor.

MeSH terms

Acylation
Alkylation
Cell Survival / drug effects
Models, Molecular
Oxazines / chemistry
Oxazines / pharmacology*
Serine Endopeptidases / drug effects*
Serine Proteinase Inhibitors / chemistry
Serine Proteinase Inhibitors / pharmacology*
Spectrometry, Mass, Fast Atom Bombardment
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

Oxazines
Serine Proteinase Inhibitors
Serine Endopeptidases
assemblin