Discovery of aminoheterocycles as a novel β-secretase inhibitor class: pH dependence on binding activity part 1

A novel series of heteroaromatic BACE-1 inhibitors is described. These inhibitors interact with the enzyme in a unique fashion that allows for potent binding in a non-traditional paradigm. In addition to the elucidation of their binding profile, a pH dependent effect on the binding affinity as a res...

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 19; no. 11; pp. 2977 - 2980
Main Authors:	Stachel, Shawn J., Coburn, Craig A., Rush, Diane, Jones, Kristen L.G., Zhu, Hong, Rajapakse, Hemaka, Graham, Samuel L., Simon, Adam, Katharine Holloway, M., Allison, Tim J., Munshi, Sanjeev K., Espeseth, Amy S., Zuck, Paul, Colussi, Dennis, Wolfe, Abigail, Pietrak, Beth L., Lai, Ming-Tain, Vacca, Joseph P.
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Ltd 01-06-2009 Elsevier
Subjects:	Alzheimer’s disease Aminoheterocycles Amyloid Precursor Protein Secretases - antagonists & inhibitors Amyloid Precursor Protein Secretases - metabolism b-Secretase BACE-1 Biological and medical sciences Crystallography, X-Ray Drug Design Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology Heterocyclic Compounds - chemistry Heterocyclic Compounds - pharmacology Hydrogen-Ion Concentration Medical sciences Neuropharmacology Pharmacology. Drug treatments Protein Binding Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopharmacology Structure-Activity Relationship b-Secretase Aminoheterocycles Alzheimer’s disease BACE-1 Nitro compound Five membered ring Nitrogen heterocycle Modeling Structure activity relation Chlorine Organic compounds Molecular model pH β-secretase Aspartic endopeptidases Alzheimer's disease Ether Enzyme Benzene derivatives Enzyme inhibitor Inhibitor enzyme complex Antialzheimer agent In vitro Amyloid precursor protein Peptidases Medium effect Hydrolases
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