Inhibition of HSV-1 protease by benzoxazinones

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 20, 1996, Pages 2463-2466

  Jarvest, Richard L ^a   Parratt, Martin J ^a   Debouck, Christine M ^a   Gorniak, Joselina G ^a   Jennings, L John ^a   Serafinowska, Halina T ^a   Strickler, James E ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; BENZOXAZINONE DERIVATIVE; PROTEINASE;

ANTIVIRAL ACTIVITY; ARTICLE; CHIRALITY; DRUG DESIGN; DRUG STABILITY; DRUG SYNTHESIS; ENZYME INHIBITION; HERPES SIMPLEX VIRUS 1; QUANTITATIVE STRUCTURE ACTIVITY RELATION;

HERPES; HUMAN HERPESVIRUS 1;

EID: 0030598194     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00455-6     Document Type: Article

References (14)

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12. 7. A solution of inhibitor was added to HSV-1 protease (protease domain of the UL26 protein, residues 1 to 247, with the addition of an amino terminal MDLPRHHHHHHS tag; 0.5 - 1 μM) diluted in buffer (50 mM sodium phosphate, 100 mM sodium chloride; pH 7.8) to give a final inhibitor concentration of 0.01 to 300 μM in a total volume of 39 μ1. Following a 30 min preincubation, of a solution of the substrate Ac-HTYLQASEKFKMWG (1 μ1) was added to give a final substrate concentration of 250 μM. The sample was incubated at 37°C for 1 h and then quenched by addition of 10% trifluoroacetic acid in water (10 μ1). The sample was analysed by HPLC to quantitate the amounts of the substrate peptide and of the N-terminal and C-terminal cleavage fragments and the percentage cleavage was calculated.
13. 8. Isocyanate parallel synthesis method: To a solution of anthranilic acid (0.41 g, 3 mmol) in dry pyridine (4 ml) at RT was added isocyanate (6.3 mmol) and the solution was heated at 70°C for 1 h. The solution was poured into water (50 ml) and the precipitate was filtered, washed with water and hexane and dried.
14. 9. Carpino, L.A. J. Am. Chem. Soc., 1993, 115, 4397.