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Publication DateMedicinal Research Reviews, ISSN 0198-6325, 01/2013, Volume 33, Issue 1, pp. 139 - 189
With 27 million cases worldwide documented in 2006, Alzheimer's disease (AD) constitutes an overwhelming health, social, economic, and political problem to...
antioxidant drugs | CDK5 inhibitors | anti‐inflammatory drugs | AChE peripheral anionic site | CK‐1 inhibitors | ERK2‐inhibitors | Ca2+ dyshomeostasis | BACE‐1 inhibitors | amyloid–β antiaggregating agents | NSAIDs | neuroprotection | multitarget drugs | GSK‐3β inhibitors | dual AChE inhibitors | metal chelators | Alzheimer's disease | Ca2+ overload | oxidative stress | multiactive compounds | 1,4‐dihydropyridines | voltage‐dependent calcium channels | Neuroprotection | Oxidative stress | Dual AChE inhibitors | Anti-inflammatory drugs | GSK-3β inhibitors | Antioxidant drugs | overload | Metal chelators | Multitarget drugs | Voltage-dependent calcium channels | CK-1 inhibitors | BACE-1 inhibitors | dyshomeostasis | 1,4-dihydropyridines | ERK2-inhibitors | Multiactive compounds | Amyloid-β antiaggregating agents | GSK-3 ss inhibitors | anti-inflammatory drugs | voltage-dependent calcium channels | TYROSINE KINASE INHIBITOR | PHARMACOLOGY & PHARMACY | CENTRAL-NERVOUS-SYSTEM | POTENT ACETYLCHOLINESTERASE INHIBITORS | amyloid-ss antiaggregating agents | M1 MUSCARINIC AGONISTS | CHEMISTRY, MEDICINAL | AMYLOID PRECURSOR PROTEIN | MOLECULAR MODELING INVESTIGATIONS | HERPES-SIMPLEX-VIRUS | TACRINE-DIHYDROPYRIDINE HYBRIDS | PERIPHERAL ANIONIC SITE | NMDA RECEPTOR ANTAGONIST | Calcium Channels - metabolism | Humans | Enzyme Inhibitors - pharmacology | Alzheimer Disease - drug therapy | tau Proteins - metabolism | Receptors, N-Methyl-D-Aspartate | Alzheimer Disease - enzymology | Enzyme Inhibitors - therapeutic use | Disease Progression | Alzheimer Disease - pathology | Amyloid Precursor Protein Secretases - metabolism | Butyrylcholinesterase - metabolism | Amyloid beta-Peptides - metabolism | Ligands | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Binding Sites | Acetylcholinesterase - metabolism | Care and treatment | Calcium channels | Glycogen | Development and progression | Glutamate | Target marketing | Antioxidants | Methyl aspartate | Enzyme inhibitors | Synthesis | Surface active agents | Drug therapy | Cancer
antioxidant drugs | CDK5 inhibitors | anti‐inflammatory drugs | AChE peripheral anionic site | CK‐1 inhibitors | ERK2‐inhibitors | Ca2+ dyshomeostasis | BACE‐1 inhibitors | amyloid–β antiaggregating agents | NSAIDs | neuroprotection | multitarget drugs | GSK‐3β inhibitors | dual AChE inhibitors | metal chelators | Alzheimer's disease | Ca2+ overload | oxidative stress | multiactive compounds | 1,4‐dihydropyridines | voltage‐dependent calcium channels | Neuroprotection | Oxidative stress | Dual AChE inhibitors | Anti-inflammatory drugs | GSK-3β inhibitors | Antioxidant drugs | overload | Metal chelators | Multitarget drugs | Voltage-dependent calcium channels | CK-1 inhibitors | BACE-1 inhibitors | dyshomeostasis | 1,4-dihydropyridines | ERK2-inhibitors | Multiactive compounds | Amyloid-β antiaggregating agents | GSK-3 ss inhibitors | anti-inflammatory drugs | voltage-dependent calcium channels | TYROSINE KINASE INHIBITOR | PHARMACOLOGY & PHARMACY | CENTRAL-NERVOUS-SYSTEM | POTENT ACETYLCHOLINESTERASE INHIBITORS | amyloid-ss antiaggregating agents | M1 MUSCARINIC AGONISTS | CHEMISTRY, MEDICINAL | AMYLOID PRECURSOR PROTEIN | MOLECULAR MODELING INVESTIGATIONS | HERPES-SIMPLEX-VIRUS | TACRINE-DIHYDROPYRIDINE HYBRIDS | PERIPHERAL ANIONIC SITE | NMDA RECEPTOR ANTAGONIST | Calcium Channels - metabolism | Humans | Enzyme Inhibitors - pharmacology | Alzheimer Disease - drug therapy | tau Proteins - metabolism | Receptors, N-Methyl-D-Aspartate | Alzheimer Disease - enzymology | Enzyme Inhibitors - therapeutic use | Disease Progression | Alzheimer Disease - pathology | Amyloid Precursor Protein Secretases - metabolism | Butyrylcholinesterase - metabolism | Amyloid beta-Peptides - metabolism | Ligands | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Binding Sites | Acetylcholinesterase - metabolism | Care and treatment | Calcium channels | Glycogen | Development and progression | Glutamate | Target marketing | Antioxidants | Methyl aspartate | Enzyme inhibitors | Synthesis | Surface active agents | Drug therapy | Cancer
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Loading RightsJournal of Medicinal Chemistry, ISSN 0022-2623, 04/2018, Volume 61, Issue 8, pp. 3491 - 3502
BACE1 is responsible for the first step in APP proteolysis, leading to toxic Aβ production, and has been indicated to play a key role in the pathogenesis of...
BETA-SECRETASE | APP GENE | CHEMISTRY, MEDICINAL | SECRETASE BACE-1 INHIBITORS | ALZHEIMERS-DISEASE | CRYSTAL-STRUCTURE | DRUG DISCOVERY | MUTATION | A-BETA | OPTIMIZATION | AMYLOID PRECURSOR PROTEIN | Index Medicus
BETA-SECRETASE | APP GENE | CHEMISTRY, MEDICINAL | SECRETASE BACE-1 INHIBITORS | ALZHEIMERS-DISEASE | CRYSTAL-STRUCTURE | DRUG DISCOVERY | MUTATION | A-BETA | OPTIMIZATION | AMYLOID PRECURSOR PROTEIN | Index Medicus
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Loading RightsCurrent Topics in Medicinal Chemistry, ISSN 1568-0266, 2013, Volume 13, Issue 15, pp. 1787 - 1807
Effective treatment of Alzheimer's disease (AD) remains a critical unmet need in medicine. The lack of useful treatment for AD led to an intense search for...
Peptidomimetic inhibitors | β-secretase | Protease inhibitors | Small-molecule inhibitors | Alzheimer's disease | BACE-1 | CHEMISTRY, MEDICINAL | ALZHEIMERS-DISEASE | X-RAY-STRUCTURE | AMYLOID PRECURSOR PROTEIN | peptidomimetic inhibitors | APP-CLEAVING ENZYME | HYDROXY ETHYLAMINES HEAS | beta-secretase | WILD-TYPE MICE | protease inhibitors | BIOLOGICAL EVALUATION | IN-VIVO EVALUATION | CARBINAMINE BACE-1 INHIBITORS | small-molecule inhibitors | STRUCTURE-BASED DESIGN
Peptidomimetic inhibitors | β-secretase | Protease inhibitors | Small-molecule inhibitors | Alzheimer's disease | BACE-1 | CHEMISTRY, MEDICINAL | ALZHEIMERS-DISEASE | X-RAY-STRUCTURE | AMYLOID PRECURSOR PROTEIN | peptidomimetic inhibitors | APP-CLEAVING ENZYME | HYDROXY ETHYLAMINES HEAS | beta-secretase | WILD-TYPE MICE | protease inhibitors | BIOLOGICAL EVALUATION | IN-VIVO EVALUATION | CARBINAMINE BACE-1 INHIBITORS | small-molecule inhibitors | STRUCTURE-BASED DESIGN
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JOURNAL OF NEUROCHEMISTRY, ISSN 0022-3042, 01/2012, Volume 120, pp. 71 - 83
beta-Secretase (memapsin 2; BACE-1) is the first protease in the processing of amyloid precursor protein leading to the production of amyloid-beta (A beta) in...
memapsin 2 | MEMAPSIN-2 BETA-SECRETASE | BACE 1 | inhibitors | drugs | BIOCHEMISTRY & MOLECULAR BIOLOGY | X-RAY-STRUCTURE | AMYLOID PRECURSOR PROTEIN | POTENT INHIBITORS | NEUROSCIENCES | HYDROXY ETHYLAMINES HEAS | beta-secretase | MOUSE MODEL | A-BETA | PEPTIDOMIMETIC INHIBITORS | Alzheimer's disease | BACE-1 INHIBITORS | STRUCTURE-BASED DESIGN
memapsin 2 | MEMAPSIN-2 BETA-SECRETASE | BACE 1 | inhibitors | drugs | BIOCHEMISTRY & MOLECULAR BIOLOGY | X-RAY-STRUCTURE | AMYLOID PRECURSOR PROTEIN | POTENT INHIBITORS | NEUROSCIENCES | HYDROXY ETHYLAMINES HEAS | beta-secretase | MOUSE MODEL | A-BETA | PEPTIDOMIMETIC INHIBITORS | Alzheimer's disease | BACE-1 INHIBITORS | STRUCTURE-BASED DESIGN
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Loading RightsEuropean Journal of Medicinal Chemistry, ISSN 0223-5234, 09/2017, Volume 137, pp. 462 - 475
In this work, a series of 2-substituted-thio- -(4-substituted-thiazol/1 -imidazol-2-yl)acetamide derivatives were developed as -secretase (BACE-1) inhibitors....
BBB | Surface Plasmon Resonance (SPR) | BACE-1 inhibitors | Docking study | Permeability | PAMPA | Alzheimer's disease | BETA-SECRETASE | CHEMISTRY, MEDICINAL | ALZHEIMERS-DISEASE | SS-SECRETASE INHIBITORS | DRUG DESIGN | BLOOD-BRAIN-BARRIER | DISCOVERY | IN-VITRO EVALUATION | DERIVATIVES | PROTEASE | STRUCTURE-BASED DESIGN | Cell Survival - drug effects | Aspartic Acid Endopeptidases - antagonists & inhibitors | Humans | Enzyme Inhibitors - pharmacology | Acetamides - pharmacology | Structure-Activity Relationship | Enzyme Inhibitors - chemical synthesis | Dose-Response Relationship, Drug | Acetamides - chemical synthesis | Amyloid Precursor Protein Secretases - metabolism | Acetamides - chemistry | Aspartic Acid Endopeptidases - metabolism | Enzyme Inhibitors - chemistry | HEK293 Cells | Molecular Docking Simulation | Molecular Structure | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Biomimetics | Amides
BBB | Surface Plasmon Resonance (SPR) | BACE-1 inhibitors | Docking study | Permeability | PAMPA | Alzheimer's disease | BETA-SECRETASE | CHEMISTRY, MEDICINAL | ALZHEIMERS-DISEASE | SS-SECRETASE INHIBITORS | DRUG DESIGN | BLOOD-BRAIN-BARRIER | DISCOVERY | IN-VITRO EVALUATION | DERIVATIVES | PROTEASE | STRUCTURE-BASED DESIGN | Cell Survival - drug effects | Aspartic Acid Endopeptidases - antagonists & inhibitors | Humans | Enzyme Inhibitors - pharmacology | Acetamides - pharmacology | Structure-Activity Relationship | Enzyme Inhibitors - chemical synthesis | Dose-Response Relationship, Drug | Acetamides - chemical synthesis | Amyloid Precursor Protein Secretases - metabolism | Acetamides - chemistry | Aspartic Acid Endopeptidases - metabolism | Enzyme Inhibitors - chemistry | HEK293 Cells | Molecular Docking Simulation | Molecular Structure | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Biomimetics | Amides
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Loading RightsBioorganic & Medicinal Chemistry Letters, ISSN 0960-894X, 08/2013, Volume 23, Issue 16, pp. 4674 - 4679
The structure activity relationship of the prime region of conformationally restricted hydroxyethylamine (HEA) BACE inhibitors is described. Variation of the...
Cat-D | Chromane | Alzheimer’s disease | Hydroxyethylamine | BACE-1 | Beta-secratase inhibitor | Alzheimer's disease | POTENT | CHEMISTRY, MEDICINAL | CHEMISTRY, ORGANIC | MICE | BETA-SECRETASE INHIBITORS | Ethylamines - pharmacology | Aspartic Acid Endopeptidases - antagonists & inhibitors | Cells, Cultured | Models, Molecular | Ethylamines - chemical synthesis | Structure-Activity Relationship | Enzyme Inhibitors - chemical synthesis | Drug Design | Inhibitory Concentration 50 | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Ethylamines - chemistry | Binding Sites | Chromans - chemistry | Permeability
Cat-D | Chromane | Alzheimer’s disease | Hydroxyethylamine | BACE-1 | Beta-secratase inhibitor | Alzheimer's disease | POTENT | CHEMISTRY, MEDICINAL | CHEMISTRY, ORGANIC | MICE | BETA-SECRETASE INHIBITORS | Ethylamines - pharmacology | Aspartic Acid Endopeptidases - antagonists & inhibitors | Cells, Cultured | Models, Molecular | Ethylamines - chemical synthesis | Structure-Activity Relationship | Enzyme Inhibitors - chemical synthesis | Drug Design | Inhibitory Concentration 50 | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Ethylamines - chemistry | Binding Sites | Chromans - chemistry | Permeability
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Loading RightsBioorganic & Medicinal Chemistry, ISSN 0968-0896, 2009, Volume 17, Issue 4, pp. 1600 - 1613
Novel dual inhibitors of acetylcholinesterase and β-secretase were design, synthesis and biological evaluation. Among them, compound exhibited good dual...
AChE | Dual inhibitor | HEA | BACE-1 | HMC | TARGET-DIRECTED LIGANDS | CHEMISTRY, MEDICINAL | BIOCHEMISTRY & MOLECULAR BIOLOGY | X-RAY-STRUCTURE | CHEMISTRY, ORGANIC | POTENT INHIBITORS | BACE1 INHIBITORS | COMBAT ALZHEIMERS-DISEASE | PEPTIDOMIMETIC INHIBITORS | POLYAMINE BACKBONE | ANTIACETYLCHOLINESTERASE ACTIVITY | COUMARIN DERIVATIVES | AMYLOID AGGREGATION | Cell Line | Humans | Cholinesterase Inhibitors - chemistry | Alzheimer Disease - drug therapy | Models, Molecular | Protease Inhibitors - chemistry | Rats | Mice, Transgenic | Cholinesterase Inhibitors - chemical synthesis | Acetylcholinesterase - chemistry | Alzheimer Disease - enzymology | Amyloid Precursor Protein Secretases - chemistry | Mice, Knockout | Protease Inhibitors - pharmacology | Amyloid Precursor Protein Secretases - metabolism | Animals | Cholinesterase Inhibitors - pharmacology | Drug Design | Mice | Protease Inhibitors - chemical synthesis | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Acetylcholinesterase - metabolism
AChE | Dual inhibitor | HEA | BACE-1 | HMC | TARGET-DIRECTED LIGANDS | CHEMISTRY, MEDICINAL | BIOCHEMISTRY & MOLECULAR BIOLOGY | X-RAY-STRUCTURE | CHEMISTRY, ORGANIC | POTENT INHIBITORS | BACE1 INHIBITORS | COMBAT ALZHEIMERS-DISEASE | PEPTIDOMIMETIC INHIBITORS | POLYAMINE BACKBONE | ANTIACETYLCHOLINESTERASE ACTIVITY | COUMARIN DERIVATIVES | AMYLOID AGGREGATION | Cell Line | Humans | Cholinesterase Inhibitors - chemistry | Alzheimer Disease - drug therapy | Models, Molecular | Protease Inhibitors - chemistry | Rats | Mice, Transgenic | Cholinesterase Inhibitors - chemical synthesis | Acetylcholinesterase - chemistry | Alzheimer Disease - enzymology | Amyloid Precursor Protein Secretases - chemistry | Mice, Knockout | Protease Inhibitors - pharmacology | Amyloid Precursor Protein Secretases - metabolism | Animals | Cholinesterase Inhibitors - pharmacology | Drug Design | Mice | Protease Inhibitors - chemical synthesis | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Acetylcholinesterase - metabolism
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Loading RightsJournal of Medicinal Chemistry, ISSN 0022-2623, 09/2007, Volume 50, Issue 18, pp. 4261 - 4264
A new aspartic protease inhibitory chemotype bearing a 2-amino-3,4-dihydroquinazoline ring was identified by high-throughput screening for the inhibition of...
SECRETASE BACE-1 | POTENT | CHEMISTRY, MEDICINAL | X-RAY CRYSTALLOGRAPHY | LIGANDS | ALZHEIMERS-DISEASE | IN-VIVO | AMYLOID PRECURSOR PROTEIN | EXPRESSION | DISCOVERY | BRAIN | Quinazolines - chemical synthesis | Cricetulus | Stereoisomerism | Humans | Molecular Conformation | Amyloid beta-Peptides - secretion | Cell Membrane Permeability | Crystallography, X-Ray | Structure-Activity Relationship | Amyloid beta-Peptides - blood | Peptide Fragments - blood | Oligopeptides - chemistry | Quinazolines - chemistry | CHO Cells | Caco-2 Cells | Aspartic Acid Endopeptidases - chemistry | Cricetinae | Aspartic Acid Endopeptidases - antagonists & inhibitors | Peptide Fragments - secretion | Models, Molecular | Rats | Amyloid Precursor Protein Secretases - chemistry | Amyloid beta-Peptides - antagonists & inhibitors | Amyloid beta-Protein Precursor - genetics | Animals | Hydrogen Bonding | Peptide Fragments - antagonists & inhibitors | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Mutation | Quinazolines - pharmacology
SECRETASE BACE-1 | POTENT | CHEMISTRY, MEDICINAL | X-RAY CRYSTALLOGRAPHY | LIGANDS | ALZHEIMERS-DISEASE | IN-VIVO | AMYLOID PRECURSOR PROTEIN | EXPRESSION | DISCOVERY | BRAIN | Quinazolines - chemical synthesis | Cricetulus | Stereoisomerism | Humans | Molecular Conformation | Amyloid beta-Peptides - secretion | Cell Membrane Permeability | Crystallography, X-Ray | Structure-Activity Relationship | Amyloid beta-Peptides - blood | Peptide Fragments - blood | Oligopeptides - chemistry | Quinazolines - chemistry | CHO Cells | Caco-2 Cells | Aspartic Acid Endopeptidases - chemistry | Cricetinae | Aspartic Acid Endopeptidases - antagonists & inhibitors | Peptide Fragments - secretion | Models, Molecular | Rats | Amyloid Precursor Protein Secretases - chemistry | Amyloid beta-Peptides - antagonists & inhibitors | Amyloid beta-Protein Precursor - genetics | Animals | Hydrogen Bonding | Peptide Fragments - antagonists & inhibitors | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Mutation | Quinazolines - pharmacology
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Loading RightsJournal of Medicinal Chemistry, ISSN 0022-2623, 11/2012, Volume 55, Issue 21, pp. 9195 - 9207
The structure-based design, synthesis, and X-ray structure of protein–ligand complexes of exceptionally potent and selective β-secretase inhibitors are...
CHEMISTRY, MEDICINAL | CATHEPSIN-D | ALZHEIMERS-DISEASE | BACE-1 INHIBITORS | 2ND-GENERATION | Amides - pharmacology | Phthalic Acids - chemistry | Sulfonamides - chemistry | Amides - chemical synthesis | Stereoisomerism | Humans | Cell Membrane Permeability | Indoles - chemical synthesis | Models, Molecular | Crystallography, X-Ray | Structure-Activity Relationship | Sulfonamides - pharmacology | Sulfonamides - chemical synthesis | Drug Design | Amides - chemistry | Cell Line, Tumor | Indoles - pharmacology | Ligands | Molecular Structure | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Phthalic Acids - pharmacology | Phthalic Acids - chemical synthesis | Indoles - chemistry
CHEMISTRY, MEDICINAL | CATHEPSIN-D | ALZHEIMERS-DISEASE | BACE-1 INHIBITORS | 2ND-GENERATION | Amides - pharmacology | Phthalic Acids - chemistry | Sulfonamides - chemistry | Amides - chemical synthesis | Stereoisomerism | Humans | Cell Membrane Permeability | Indoles - chemical synthesis | Models, Molecular | Crystallography, X-Ray | Structure-Activity Relationship | Sulfonamides - pharmacology | Sulfonamides - chemical synthesis | Drug Design | Amides - chemistry | Cell Line, Tumor | Indoles - pharmacology | Ligands | Molecular Structure | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Phthalic Acids - pharmacology | Phthalic Acids - chemical synthesis | Indoles - chemistry
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Loading RightsJournal of Medicinal Chemistry, ISSN 0022-2623, 10/2006, Volume 49, Issue 21, pp. 6147 - 6150
A macrocyclic inhibitor of β-secretase was designed by covalently cross-linking the P1 and P3 side chains of an isophthalamide-based inhibitor....
THERAPEUTICS | DESIGN | CHEMISTRY, MEDICINAL | PROTEIN | ALZHEIMERS-DISEASE | BACE-1 | GENERATION | MICE | BRAIN | Phthalic Acids - chemistry | Macrocyclic Compounds - chemistry | Protease Inhibitors - pharmacokinetics | Stereoisomerism | Molecular Conformation | Macrocyclic Compounds - pharmacokinetics | Protease Inhibitors - chemistry | Structure-Activity Relationship | Macrocyclic Compounds - chemical synthesis | Brain - metabolism | Tissue Distribution | Amyloid Precursor Protein Secretases - metabolism | Animals | Amyloid beta-Peptides - metabolism | Amides - chemistry | Mice | Protease Inhibitors - chemical synthesis | Blood-Brain Barrier
THERAPEUTICS | DESIGN | CHEMISTRY, MEDICINAL | PROTEIN | ALZHEIMERS-DISEASE | BACE-1 | GENERATION | MICE | BRAIN | Phthalic Acids - chemistry | Macrocyclic Compounds - chemistry | Protease Inhibitors - pharmacokinetics | Stereoisomerism | Molecular Conformation | Macrocyclic Compounds - pharmacokinetics | Protease Inhibitors - chemistry | Structure-Activity Relationship | Macrocyclic Compounds - chemical synthesis | Brain - metabolism | Tissue Distribution | Amyloid Precursor Protein Secretases - metabolism | Animals | Amyloid beta-Peptides - metabolism | Amides - chemistry | Mice | Protease Inhibitors - chemical synthesis | Blood-Brain Barrier
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Loading RightsBioorganic & Medicinal Chemistry, ISSN 0968-0896, 07/2012, Volume 20, Issue 14, pp. 4377 - 4389
A series of P1–P3 linked macrocyclic BACE-1 inhibitors containing a hydroxyethylamine (HEA) isostere scaffold has been synthesized. All inhibitors comprise a...
Hydroxyethylamine (HEA) isostere | Alzheimer’s disease | BACE-1 inhibition | Macrocycles | Alzheimer's disease | THERAPEUTICS | CELLS | CHEMISTRY, MEDICINAL | BETA-SECRETASE BACE-1 | SAR | ALZHEIMERS-DISEASE | BIOCHEMISTRY & MOLECULAR BIOLOGY | CHEMISTRY, ORGANIC | PEPTIDOMIMETIC INHIBITORS | MICE | BRAIN | PROTEASE | Protein Structure, Tertiary | Amyloid Precursor Protein Secretases - metabolism | Enzyme Inhibitors - chemistry | Drug Design | Crystallography, X-Ray | Ethylamines - chemical synthesis | Structure-Activity Relationship | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Ethylamines - chemistry | Enzyme Inhibitors - chemical synthesis | Binding Sites | Enzymes | Chemical inhibitors | Enzyme inhibitors | Structure | Crystals | Crystal structure
Hydroxyethylamine (HEA) isostere | Alzheimer’s disease | BACE-1 inhibition | Macrocycles | Alzheimer's disease | THERAPEUTICS | CELLS | CHEMISTRY, MEDICINAL | BETA-SECRETASE BACE-1 | SAR | ALZHEIMERS-DISEASE | BIOCHEMISTRY & MOLECULAR BIOLOGY | CHEMISTRY, ORGANIC | PEPTIDOMIMETIC INHIBITORS | MICE | BRAIN | PROTEASE | Protein Structure, Tertiary | Amyloid Precursor Protein Secretases - metabolism | Enzyme Inhibitors - chemistry | Drug Design | Crystallography, X-Ray | Ethylamines - chemical synthesis | Structure-Activity Relationship | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Ethylamines - chemistry | Enzyme Inhibitors - chemical synthesis | Binding Sites | Enzymes | Chemical inhibitors | Enzyme inhibitors | Structure | Crystals | Crystal structure
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Loading RightsJOURNAL OF MOLECULAR MODELING, ISSN 1610-2940, 08/2017, Volume 23, Issue 8, p. 239
BACE-1 and GSK-3 beta are potential therapeutic drug targets for Alzheimer's disease. Recently, both the targets received attention for designing dual...
MEMAPSIN-2 BETA-SECRETASE | BACE-1 and GSK-3 beta | TARGET-DIRECTED LIGANDS | DESIGN | Dual inhibitor | Binding energy analysis | HIGH-THROUGHPUT | DOCKING | BIOCHEMISTRY & MOLECULAR BIOLOGY | DRUG DISCOVERY | Molecular dynamics simulation | CHEMISTRY, MULTIDISCIPLINARY | GLYCOGEN-SYNTHASE KINASE-3-BETA | COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS | BIOPHYSICS | Network analysis | BIOLOGICAL EVALUATION | IN-VIVO ACTIVITIES | Alzheimer's disease | DERIVATIVES
MEMAPSIN-2 BETA-SECRETASE | BACE-1 and GSK-3 beta | TARGET-DIRECTED LIGANDS | DESIGN | Dual inhibitor | Binding energy analysis | HIGH-THROUGHPUT | DOCKING | BIOCHEMISTRY & MOLECULAR BIOLOGY | DRUG DISCOVERY | Molecular dynamics simulation | CHEMISTRY, MULTIDISCIPLINARY | GLYCOGEN-SYNTHASE KINASE-3-BETA | COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS | BIOPHYSICS | Network analysis | BIOLOGICAL EVALUATION | IN-VIVO ACTIVITIES | Alzheimer's disease | DERIVATIVES
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Loading RightsBioorganic & Medicinal Chemistry Letters, ISSN 0960-894X, 07/2018, Volume 28, Issue 12, pp. 2195 - 2200
New amino-1,4-oxazine derived BACE-1 inhibitors were explored and various synthetic routes developed. The binding mode of the inhibitors was elucidated by...
Amino-1,4-oxazines | P-gp | Alzheimer’s disease | BACE-1 | pKa | Alzheimer's disease | SECRETASE | SITE | CHEMISTRY, MEDICINAL | PRECURSOR | LEAD GENERATION | ALZHEIMERS-DISEASE | CHEMISTRY, ORGANIC | AMYLOID BETA-PEPTIDES | IN-VIVO REDUCTION | p-gp | pK(a) | HYDROXYETHYLAMINES | DERIVATIVES | STRUCTURE-BASED DESIGN | Aspartic Acid Endopeptidases - antagonists & inhibitors | Molecular Conformation | Enzyme Inhibitors - pharmacology | Models, Molecular | Structure-Activity Relationship | Enzyme Inhibitors - chemical synthesis | Drug Discovery | Madin Darby Canine Kidney Cells - drug effects | Dose-Response Relationship, Drug | Amyloid Precursor Protein Secretases - metabolism | Animals | Aspartic Acid Endopeptidases - metabolism | Enzyme Inhibitors - chemistry | Dogs | Mice | Oxazines - chemistry | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Oxazines - chemical synthesis | Oxazines - pharmacology | Medicine, Experimental | Medical research | Research institutes | Analysis
Amino-1,4-oxazines | P-gp | Alzheimer’s disease | BACE-1 | pKa | Alzheimer's disease | SECRETASE | SITE | CHEMISTRY, MEDICINAL | PRECURSOR | LEAD GENERATION | ALZHEIMERS-DISEASE | CHEMISTRY, ORGANIC | AMYLOID BETA-PEPTIDES | IN-VIVO REDUCTION | p-gp | pK(a) | HYDROXYETHYLAMINES | DERIVATIVES | STRUCTURE-BASED DESIGN | Aspartic Acid Endopeptidases - antagonists & inhibitors | Molecular Conformation | Enzyme Inhibitors - pharmacology | Models, Molecular | Structure-Activity Relationship | Enzyme Inhibitors - chemical synthesis | Drug Discovery | Madin Darby Canine Kidney Cells - drug effects | Dose-Response Relationship, Drug | Amyloid Precursor Protein Secretases - metabolism | Animals | Aspartic Acid Endopeptidases - metabolism | Enzyme Inhibitors - chemistry | Dogs | Mice | Oxazines - chemistry | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Oxazines - chemical synthesis | Oxazines - pharmacology | Medicine, Experimental | Medical research | Research institutes | Analysis
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Loading RightsBioorganic & Medicinal Chemistry Letters, ISSN 0960-894X, 06/2017, Volume 27, Issue 11, pp. 2432 - 2438
A series of BACE1 inhibitors incorporating mono- and bicyclic 2-oxopiperazines is described. Inhibitor showed an enzyme K of 2 nM and a cellular EC value of...
β-Secretase | Alzheimer’s disease | Protease inhibitors | BACE-1 | Memapsin 2 | Alzheimer's disease | THERAPEUTICS | CHEMISTRY, MEDICINAL | beta-Secretase | PROTEIN | ALZHEIMERS-DISEASE | CRYSTAL-STRUCTURE | CHEMISTRY, ORGANIC | ALDEHYDES | POTENT | PIPERAZINONE | PROGRESS | GENERATION | BETA-SECRETASE INHIBITORS | Phthalic Acids - chemistry | Aspartic Acid Endopeptidases - antagonists & inhibitors | Piperazines - chemical synthesis | Piperazines - chemistry | Structure-Activity Relationship | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Phthalic Acids - chemical synthesis | inhibitor | piperazinones | design | β-secretase | secretase
β-Secretase | Alzheimer’s disease | Protease inhibitors | BACE-1 | Memapsin 2 | Alzheimer's disease | THERAPEUTICS | CHEMISTRY, MEDICINAL | beta-Secretase | PROTEIN | ALZHEIMERS-DISEASE | CRYSTAL-STRUCTURE | CHEMISTRY, ORGANIC | ALDEHYDES | POTENT | PIPERAZINONE | PROGRESS | GENERATION | BETA-SECRETASE INHIBITORS | Phthalic Acids - chemistry | Aspartic Acid Endopeptidases - antagonists & inhibitors | Piperazines - chemical synthesis | Piperazines - chemistry | Structure-Activity Relationship | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Phthalic Acids - chemical synthesis | inhibitor | piperazinones | design | β-secretase | secretase
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Loading RightsJournal of Medicinal Chemistry, ISSN 0022-2623, 07/2007, Volume 50, Issue 15, pp. 3431 - 3433
β-Secretase inhibition offers an exciting opportunity for therapeutic intervention in the progression of Alzheimer's disease. A series of isonicotinamides...
THERAPEUTICS | POTENT | CHEMISTRY, MEDICINAL | ASPARTYL PROTEASE | ALZHEIMERS-DISEASE | BACE-1 | ARYL HALIDES | ENHANCEMENT | PRECURSOR PROTEIN | IDENTIFICATION | CLEAVAGE | Amides - pharmacology | Peptide Fragments - metabolism | Amides - chemical synthesis | Rats | Biological Availability | Structure-Activity Relationship | Isonicotinic Acids - chemical synthesis | Isonicotinic Acids - pharmacology | Brain - metabolism | Dose-Response Relationship, Drug | Animals | Amyloid beta-Peptides - metabolism | Amides - chemistry | Mice | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Isonicotinic Acids - pharmacokinetics
THERAPEUTICS | POTENT | CHEMISTRY, MEDICINAL | ASPARTYL PROTEASE | ALZHEIMERS-DISEASE | BACE-1 | ARYL HALIDES | ENHANCEMENT | PRECURSOR PROTEIN | IDENTIFICATION | CLEAVAGE | Amides - pharmacology | Peptide Fragments - metabolism | Amides - chemical synthesis | Rats | Biological Availability | Structure-Activity Relationship | Isonicotinic Acids - chemical synthesis | Isonicotinic Acids - pharmacology | Brain - metabolism | Dose-Response Relationship, Drug | Animals | Amyloid beta-Peptides - metabolism | Amides - chemistry | Mice | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Isonicotinic Acids - pharmacokinetics
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Loading RightsJournal of Chromatography A, ISSN 0021-9673, 03/2017, Volume 1487, pp. 235 - 241
In this work a novel capillary electrophoresis-mass spectrometry (CE-MS) based method was developed and validated for the assay of β-secretase (BACE1) activity...
β-secretase | Kinetics | Inhibition | Alzheimer’s disease | Capillary electrophoresis | Mass spectrometry detection | Alzheimer's disease | CHEMISTRY, ANALYTICAL | BIOCHEMICAL RESEARCH METHODS | AMYLOID PRECURSOR PROTEIN | PEPTIDE | PROTEASES | IMMOBILIZED ENZYME REACTOR | beta-secretase | SUBSTRATE | CELL | BACE-1 INHIBITORS
β-secretase | Kinetics | Inhibition | Alzheimer’s disease | Capillary electrophoresis | Mass spectrometry detection | Alzheimer's disease | CHEMISTRY, ANALYTICAL | BIOCHEMICAL RESEARCH METHODS | AMYLOID PRECURSOR PROTEIN | PEPTIDE | PROTEASES | IMMOBILIZED ENZYME REACTOR | beta-secretase | SUBSTRATE | CELL | BACE-1 INHIBITORS
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Loading RightsBioorganic & Medicinal Chemistry Letters, ISSN 0960-894X, 2009, Volume 19, Issue 22, pp. 6386 - 6391
Using structure-guided design, hydroxyethylamine BACE-1 inhibitors were optimized to nanomolar Aβ cellular inhibition with selectivity against cathepsin-D....
Alzheimer’s disease | Hydroxyethylamine (HEA) | β-Secretase (BACE-1) inhibitor | Alzheimer's disease | BETA-SECRETASE | APP | THYMOCYTE DEVELOPMENT | CHEMISTRY, MEDICINAL | ALZHEIMERS-DISEASE | beta-Secretase (BACE-1) inhibitor | CHEMISTRY, ORGANIC | GAMMA-SECRETASE INHIBITORS | AMYLOID PRECURSOR PROTEIN | KNOCKOUT MICE | PEPTIDE | DIFFERENTIATION | CATHEPSIN-D DEFICIENCY | Amyloid Precursor Protein Secretases - genetics | Aspartic Acid Endopeptidases - chemistry | Aspartic Acid Endopeptidases - antagonists & inhibitors | Humans | Models, Molecular | Substrate Specificity | Structure-Activity Relationship | Aspartic Acid Endopeptidases - genetics | Amyloid Precursor Protein Secretases - chemistry | ATP-Binding Cassette, Sub-Family B, Member 1 - genetics | Drug Design | ATP-Binding Cassette, Sub-Family B, Member 1 - chemistry | Molecular Structure | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Permeability
Alzheimer’s disease | Hydroxyethylamine (HEA) | β-Secretase (BACE-1) inhibitor | Alzheimer's disease | BETA-SECRETASE | APP | THYMOCYTE DEVELOPMENT | CHEMISTRY, MEDICINAL | ALZHEIMERS-DISEASE | beta-Secretase (BACE-1) inhibitor | CHEMISTRY, ORGANIC | GAMMA-SECRETASE INHIBITORS | AMYLOID PRECURSOR PROTEIN | KNOCKOUT MICE | PEPTIDE | DIFFERENTIATION | CATHEPSIN-D DEFICIENCY | Amyloid Precursor Protein Secretases - genetics | Aspartic Acid Endopeptidases - chemistry | Aspartic Acid Endopeptidases - antagonists & inhibitors | Humans | Models, Molecular | Substrate Specificity | Structure-Activity Relationship | Aspartic Acid Endopeptidases - genetics | Amyloid Precursor Protein Secretases - chemistry | ATP-Binding Cassette, Sub-Family B, Member 1 - genetics | Drug Design | ATP-Binding Cassette, Sub-Family B, Member 1 - chemistry | Molecular Structure | Amyloid Precursor Protein Secretases - antagonists & inhibitors | Permeability
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