Abstract
Dementia caused by Alzheimers disease is a large medical burden on society in the developed world. Current treatments are largely symptomatic, and there is an urgent need for therapies which can interrupt or reverse the progression of disease. A number of strategies for intervention are being actively pursued; among the most promising is the inhibition of β-secretase, or BACE. BACE is the enzyme responsible for N-terminal cleavage of the Alzheimers precursor protein leading to the production of the beta-amyloid peptide. This cascade ultimately leads to the formation of amyloid plaques, one of the hallmark lesions of the disease. It is expected that inhibitors of BACE may therefore serve as an effective disease-modifing therapy for the treatment of AD. This concept has received significant attention by both academics and the pharmaceutical industry. This review focuses on a discussion of the reported structure-activity relationships for inhibitors of this important therapeutic target.
Keywords: alzheimers disease, statines, hydroxymethylcarbonyl isosteres, azabicyclononane hiv protease, piperazine inhibitors, macrocycles
Current Pharmaceutical Design
Title: Progress in the Discovery of BACE Inhibitors
Volume: 11 Issue: 26
Author(s): L. A. Thompson, J. J. Bronson and F. C. Zusi
Affiliation:
Keywords: alzheimers disease, statines, hydroxymethylcarbonyl isosteres, azabicyclononane hiv protease, piperazine inhibitors, macrocycles
Abstract: Dementia caused by Alzheimers disease is a large medical burden on society in the developed world. Current treatments are largely symptomatic, and there is an urgent need for therapies which can interrupt or reverse the progression of disease. A number of strategies for intervention are being actively pursued; among the most promising is the inhibition of β-secretase, or BACE. BACE is the enzyme responsible for N-terminal cleavage of the Alzheimers precursor protein leading to the production of the beta-amyloid peptide. This cascade ultimately leads to the formation of amyloid plaques, one of the hallmark lesions of the disease. It is expected that inhibitors of BACE may therefore serve as an effective disease-modifing therapy for the treatment of AD. This concept has received significant attention by both academics and the pharmaceutical industry. This review focuses on a discussion of the reported structure-activity relationships for inhibitors of this important therapeutic target.
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Cite this article as:
Thompson A. L., Bronson J. J. and Zusi C. F., Progress in the Discovery of BACE Inhibitors, Current Pharmaceutical Design 2005; 11 (26) . https://dx.doi.org/10.2174/138161205774370825
DOI https://dx.doi.org/10.2174/138161205774370825 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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