Inhibition of human cytomegalovirus protease by benzoxazinones and evidence of antiviral activity in cell culture.

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 16, 1997, Pages 2105-2108

  Abood, Norman A ^a   Schretzman, Lori A ^a   Flynn, Daniel L ^a   Houseman, Kathrine A ^a   Wittwer, Arthur J ^a   Dilworth, Vickie M ^a   Hippenmeyer, Paul J ^a   Holwerda, Barry C ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZOXAZINONE DERIVATIVE; PROTEINASE;

ANTIVIRAL ACTIVITY; ARTICLE; DRUG STABILITY; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CYTOMEGALOVIRUS; HYDROLYSIS; NONHUMAN;

EID: 0030756035     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00368-5     Document Type: Article

References (26)

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23. The hCMV protease assay employed succinyl-ala-gly-val-val-asn-ala-p-nitroanilide as substrate. Inhibitor (10 μL in DMSO) and enzyme (100 μL, 4.8 μg/mL in assay buffer [10 mM Na phosphate, 150 mM Na acetate buffer, pH 7.4, with 0.1% CHAPS and 20% glycerol]) were incubated in a 96-well assay plate (Falcon 3910) for 30 min at room temperature. Substrate (50 μL of 9 parts assay buffer and 1 part 20 mM substrate in DMSO) was then added and the absorbance at 405 nm monitored in an absorbance reader. Activities were expressed as absorbance change per minute and compared to controls lacking inhibitor.
24. 50 for gancyclovir in this assay is 8.9/>100 uM. Adler, J.; Mitten, M.; Norbeck, D.; Marsh, K.; Kern, E. R.; Clement, J. Antiviral Res. 1994, 23, 93 .
25. 50 for gancyclovir in this assay is 8.9/>100 uM. Adler, J.; Mitten, M.; Norbeck, D.; Marsh, K.; Kern, E. R.; Clement, J. Antiviral Res. 1994, 23, 93 .
26. t are the fluorescence at time zero and at time t, resectively, and k is the decay constant. Half-life was determined as the average of at least 3 separate determinations (three different plasma donors), by calculating half-life = ln(2)/k.