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Your search keyword '"Tummino PJ"' showing total 3 results
Start Over Author "Tummino PJ" Publisher elsevier science ltd
3 results on '"Tummino PJ"'

1. Nonpeptidic HIV protease inhibitors: 6-alkyl-5,6-dihydropyran-2-ones possessing a novel and achiral 3-(2-t-butyl-5-methyl-4-sulfamate)phenylthio moiety.

Author

Vara Prasad JV, Markoski LJ, Boyer FE, Domagala JM, Ellsworth EL, Gajda C, Hagen SE, Tait BD, Lunney EA, Tummino PJ, Ferguson D, Holler T, Hupe D, Nouhan C, Gracheck SJ, VanderRoest S, Saunders J, Iyer K, and Sinz M

Subjects
Animals, Disulfides chemistry, Disulfides pharmacology, HIV drug effects, HIV Protease Inhibitors chemistry, HIV Protease Inhibitors pharmacokinetics, HIV Protease Inhibitors pharmacology, Mice, Models, Molecular, Pyrones chemistry, Pyrones pharmacology, Structure-Activity Relationship, Sulfonic Acids pharmacology, Disulfides chemical synthesis, HIV Protease Inhibitors chemical synthesis, Pyrones chemical synthesis, Sulfonic Acids chemistry
Abstract

Dihydropyran-2-ones possessing a sulfamate moiety at the 4-position of the thiophenyl ring were designed to reach S3' pocket of the HIV protease. Synthetic routes for the preparation of thiotosylates possessing 3-(2-t-butyl-5-methyl-4-sulfamate) phenylthio moiety were established. SAR of various sulfamate analogs including HIV protease binding affinities, antiviral activities and therapeutic indices will be described.

Published
1999
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2. 4-hydroxy-5,6-dihydro-2H-pyran-2-ones.3. Bicyclic and hetero-aromatic ring systems as 3-position scaffolds to bind to S1' and S2' of the HIV-1 protease enzyme.

Author

Ellsworth EL, Domagala J, Prasad JV, Hagen S, Ferguson D, Holler T, Hupe D, Graham N, Nouhan C, Tummino PJ, Zeikus G, and Lunney EA

Subjects
Binding Sites, Computer Simulation, Drug Design, HIV Protease chemistry, HIV Protease Inhibitors pharmacology, Hydrocarbons, Aromatic chemistry, Hydrogen-Ion Concentration, Inhibitory Concentration 50, Models, Molecular, Molecular Structure, Pyrones metabolism, Software, Structure-Activity Relationship, Sugar Alcohols metabolism, Valine analogs & derivatives, Valine metabolism, HIV Protease metabolism, HIV Protease Inhibitors chemistry, HIV Protease Inhibitors metabolism, Pyrones chemical synthesis, Pyrones pharmacology
Abstract

5,6-Dihydro-2H-pyran-2-ones are potent inhibitors of HIV-1 protease, which bind to the S1, S2, S1', and S2' pockets and have a unique binding mode with the catalytic aspartyl groups and the flap region of the enzyme. Efforts to explore 3-position heterocyclic scaffolds that bind to the S1' and S2' pockets have provided a number of selected analogs that display high HIV-1 protease inhibitory activity. reserved.

Published
1999
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3. Nonpeptidic HIV protease inhibitors: 6-alkyl-5,6-dihydropyran-2-ones possessing achiral 3-(4-amino/carboxamide-2-t-butyl,5-methylphenyl thio) moiety: antiviral activities and pharmacokinetic properties.

Author

Vara Prasad JV, Boyer FE, Domagala JM, Ellsworth EL, Gajda C, Hagen SE, Markoski LJ, Tait BD, Lunney EA, Tummino PJ, Ferguson D, Holler T, Hupe D, Nouhan C, Gracheck SJ, VanderRoest S, Saunders J, Iyer K, Sinz M, and Brodfuehrer J

Subjects
Animals, Anti-HIV Agents pharmacology, Crystallography, X-Ray, Dogs, Inhibitory Concentration 50, Kinetics, Mice, Models, Molecular, Structure-Activity Relationship, HIV Protease Inhibitors chemical synthesis, HIV Protease Inhibitors pharmacokinetics, Pyrans chemical synthesis, Pyrans pharmacokinetics
Abstract

Dihydropyran-2-ones possessing amino and carboxamide functionalities on 3-SPh (2-tert-butyl, 5-methyl) ring were synthesized and evaluated for their antiviral activities. Both the enantiomers of inhibitor 15 were synthesized. The in vitro resistance profile, inhibitory activities against cytochrome P450 isozymes and pharmacokinetic properties of inhibitor 15S will be discussed.

Published
1999
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