Design and Syntheses of 1,6-Naphthalene Derivatives as Selective HCMV Protease Inhibitors

Journal of Medicinal Chemistry

Volumn 47, Issue 8, 2004, Pages 1893-1899

  Gopalsamy, Ariamala ^a   Lim, Kitae ^a   Ellingboe, John W ^a   Mitsner, Boris ^a   Nikitenko, Antonia ^a   Upeslacis, Janis ^a   Mansour, Tarek S ^a   Olson, Matthew W ^a   Bebernitz, Geraldine A ^a   Grinberg, Diane ^a   Feld, Boris ^a   Moy, Franklin J ^a   O'Connell, John ^a  

^a WYETH RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,6 NAPHTHALENE DERIVATIVE; ACICLOVIR; CHYMOTRYPSIN; CIDOFOVIR; ELASTASE; FORMVIRSEN; FOSCARNET; GANCICLOVIR; NAPHTHALENE DERIVATIVE; PROTEINASE INHIBITOR; TRYPSIN; UNCLASSIFIED DRUG;

ANTIVIRAL ACTIVITY; ARTICLE; COMPETITIVE INHIBITION; CONFORMATIONAL TRANSITION; DRUG DESIGN; DRUG POTENCY; DRUG SYNTHESIS; ENZYME INHIBITION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; LATENT VIRUS INFECTION; STRUCTURE ACTIVITY RELATION; VIRUS ASSEMBLY; VIRUS IDENTIFICATION; VIRUS REACTIVATION; VIRUS RESISTANCE;

2-NAPHTHYLAMINE; CYTOMEGALOVIRUS; DATABASES, FACTUAL; NAPHTHALENES; PROTEASE INHIBITORS; SERINE ENDOPEPTIDASES; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES;

EID: 11144355878     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm030540h     Document Type: Article

References (27)

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24. 18 column. Gradient: 20.5-25% ACN for 1.5 min and 25 to 95% ACN for 1 min. The quantity of substrate cleaved in each assay was derived from the empirically determined product specific activity. This value was determined as 2331 ± 89 mAu·S/nmol.
25. 50 values were determined from the reaction rates over a 20 min in 1 min intervals.
26. 2. Line-width and intensity change of the compound resonances was consistent with stoichiometric binding. Similarly the substrate (DABCLY-Arg-Gly-Val-Val-Asn-Ala-Ser-Ser-Arg-Leu-Ala-EDANS) was determined to bind stoichiometrically with inactive CMVP R166A. Stilbene I displaces the binding of the substrate.
27. Compounds were purified by HPLC and the purity was >90%. LC Conditions: HP 1100, 23°C, 10 μL injected; column: YMC-ODS-A 4.6 x 50 5 μm; gradient A: 0.05% TFA/water, B: 0.05% TFA/acetonitrile; time 0 and 1 min: 98%A and 2%B; 7 min: 10%A and 90%B; 8 min: 10%A and 90%B; 8.9 min: 98%A and 2%B; post time 1 min; flow rate 2.5 mL/min; detection: 215 and 254 nm, DAD. Semiprep HPLC: Gilson with Unipoint software; column: Phenomenex C18 Luna 21.6 mm x 60 mm, 5 μM; solvent A: water (0.02% TFA buffer); solvent B: acetonitrile (0.02% TFA buffer); solvent gradient: time 0: 5% B; 2.5 min: 5% B; 12 min: 95% B; hold 95% B 3 min; flow rate: 22.5 mL/min; detection: 215 and 254 nm.