Inhibition of human cytomegalovirus protease by enedione derivatives of thieno[2,3-d]oxazinones through a novel dual acylation/alkylation mechanism.
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.
Pinto
I L
IL
SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK. Ivan_Pinto-1@sbphrd.com
Jarvest
R L
RL
Clarke
B
B
Dabrowski
C E
CE
Fenwick
A
A
Gorczyca
M M
MM
Jennings
L J
LJ
Lavery
P
P
Sternberg
E J
EJ
Tew
D G
DG
West
A
A
D000215:Acylation; D000478:Alkylation; D002470:Cell Survival / Q000187:drug effects; D008958:Models, Molecular; D010078:Oxazines / Q000737:chemistry / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D010078:Oxazines; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; C071910:assemblin