- Highly stereoselective asymmetric aldol routes to tert-butyl-2-(3,5-difluorophenyl)-1-oxiran-2-yl)ethyl)carbamates: Building blocks for novel protease inhibitors
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Enantioselective syntheses of tert-butyl ((S)-2-(3,5-difluorophenyl)-1-((S)-oxiran-2-yl)ethyl)carbamate and ((S)-2-(3,5-difluorophenyl)-1-((R)-oxiran-2-yl)ethyl)carbamate are described. We utilized asymmetric syn- and anti-aldol reactions to set both ster
- Ghosh, Arun K.,Cárdenas, Emilio L.,Brindisi, Margherita
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p. 4062 - 4065
(2017/09/29)
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- Design, synthesis, and biological evaluation of novel fluorinated ethanolamines
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The preparation of novel fluorinated allylamines and their use as key fragments for the stereoselective synthesis of hydroxyethyl secondary amine (HEA)-type peptidomimetics is described. Our strategy employs chiral sulfinyl imines as synthesis intermediates, by treatment of hemiaminal precursors with two equivalents of vinylmagnesium bromide. The subsequent oxidation of the allylic amines to the corresponding epoxides was achieved by treatment with methyl(trifluoromethyl)dioxirane. Finally, epoxide ring opening with a range of nitrogen nucleophiles provided a library of HEA-derived peptidomimetics with a phenyldifluoromethylene moiety. The biological evaluation of these derivatives revealed compounds with remarkable BACE1 inhibitory activity. Docking studies revealed the influence of the fluorine atoms in the binding mode of the synthesized ligands. Furthermore, the biological evaluation of our final products and synthesis intermediates led to the discovery of compounds with antimicrobial activity against Mycobacterium and Nocardia species.
- Fustero, Santos,Cunat, Ana C.,Flores, Sonia,Baez, Claribel,Oliver, Judit,Cynamon, Michael,Guetschow, Michael,Mertens, Matthias D.,Delgado, Oscar,Tresadern, Gary,Trabanco, Andres A.
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scheme or table
p. 14772 - 14784
(2012/02/03)
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- BETA-SECRETASE INHIBITING COMPOUNDS
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Disclosed are compounds represented by Formula (I) as defined in the specification, or pharmaceutically acceptable salts or isomers thereof, and a pharmaceutical composition for inhibiting beta-secretase activity comprising a therapeutically effective amount of the same.
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Page/Page column 57-58
(2009/04/25)
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- BETA-SECRETASE INHIBITING COMPOUNDS HAVING OXO-DIHYDRO-PYRAZOLE MOIETY
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Disclosed are compounds represented by Formula (I) as defined in the specification, or pharmaceutically acceptable salts or isomers thereof, and a pharmaceutical composition for inhibiting beta-secretase activity comprising a therapeutically effective amo
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Page/Page column 36
(2009/04/25)
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- Methods of treatment of amyloidosis using bi-aryl aspartyl protease inhibitors
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The invention relates to novel compounds and methods of treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.
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Page/Page column 42
(2010/02/15)
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- SUBSTITUTED HYDROXYETHYLAMINE ASPARTYL PROTEASE INHIBITORS
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The invention relates to novel compounds and also to methods of treating at least one disease, disorder, or condition associated with amyloidosis using such compounds. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.
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Page/Page column 161
(2008/06/13)
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- METHODS OF TREATMENT OF AMYLOIDOSIS USING ASPARTYL-PROTEASE INHIBITORS
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The invention relates to acetyl 2-hydroxy-1,3-diaminospirocyclohexanes and derivatives thereof that are useful in treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.
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Page/Page column 193
(2010/02/13)
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- METHODS OF TREATMENT OF AMYLOIDOSIS USING BI-CYCLIC ASPARTYL PROTEASE INHIBITORS
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The invention relates to novel compounds and methods of treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.
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Page/Page column 291; 294
(2010/02/14)
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- SUBSTITUTED HYDROXYETHYLAMINE ASPARTYL PROTEASE INHIBITORS
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The invention relates to novel compounds and also to methods of treating at least one disease, disorder, or condition associated with amyloidosis using such compounds. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.
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Page/Page column 105-106; 108
(2010/02/14)
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- 1,3-DIAMINO-2-HYDROXYPROPANE PRODRUG DERIVATIVES
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The present invention relates to compounds of formula (AA), (I) and (X), useful in treating Alzheimer's disease and other similar diseases. These compounds include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer's dis
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Page 172-173
(2010/11/30)
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- HYDROXYETHYLAMINE DERIVATIVES FOR THE TREATMENT OF ALZHEIMER'S DISEASE
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The present invention relates to novel hydroxyethylamine compounds of formula (I): (I) having Asp2 (-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated-amyloid levels or-amyloid deposits, particularly Alzheimer's disease.
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- TRICYCLIC INDOLE DERIVATIVES AND THEIR USE IN THE TREATMENT OF ALZHEIMER’S DISEASE
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The present invention relates to novel hydroxyethylamine compounds having Asp2 (β-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated β- amyloid levels or β-amyloid deposits, particularly Alzheimer's disease.
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- Hydroxy alkyl amines
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Disclosed are compounds of formula X, which are useful in treating Alzheimer's disease and other similar diseases. Pharmaceutical compositions comprising compounds of formula X and methods of preparing the compounds of formula X are also disclosed.
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- Processes and intermediates for preparing benzyl epoxides
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Disclosed are intermediates and processes for preparing epoxides of the formula: where R and PROT are defined herein. These epoxides are useful as intermediates in the production of biologically active compounds, i.e., in the production of pharmaceutical
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