1. BACE-1 hydroxyethylamine inhibitors using novel edge-to-face interaction with Arg-296
- Author
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Alan Naylor, Emmanuel Hubert Demont, P. Theobald, Daryl S. Walter, G. Maile, Gareth Wayne, Ishrut Hussain, Colin Dingwall, B. Clarke, C. Howes, Sharon Sweitzer, D. Vesey, Leanne Cutler, Julie Hawkins, Rosalie Matico, J. Mosley, A. O'Brien, Virginie Soleil, Sally Redshaw, Kathrine J. Smith, Paul Rowland, and R. Dunsdon
- Subjects
Molecular model ,Stereochemistry ,medicine.drug_class ,Clinical Biochemistry ,Pharmaceutical Science ,Carboxamide ,Arginine ,Crystallography, X-Ray ,Biochemistry ,Structure-Activity Relationship ,Alzheimer Disease ,Drug Discovery ,Ethylamines ,Amyloid precursor protein ,medicine ,Animals ,Structure–activity relationship ,Computer Simulation ,Protease Inhibitors ,Binding site ,Molecular Biology ,chemistry.chemical_classification ,Binding Sites ,biology ,Organic Chemistry ,Rats ,Enzyme ,chemistry ,Enzyme inhibitor ,biology.protein ,Molecular Medicine ,Amyloid Precursor Protein Secretases ,Amyloid precursor protein secretase - Abstract
Inhibition of the aspartyl protease BACE-1 has the potential to deliver a disease-modifying therapy for Alzheimer's disease. Herein, is described a series of potent inhibitors based on an hydroxyethylamine (HEA) transition state mimetic template. These inhibitors interact with the non prime side of the enzyme using a novel edge-to-face interaction with Arg-296.
- Published
- 2010