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Development of BACE1 Inhibitors for Alzheimer's Disease

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Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. The production and accumulation of β-amyloid peptides (Aβ) from the β-amyloid precursor protein (APP) are believed to play a key role in the onset and progression of AD. BACE1 (β-site APP cleaving enzyme 1) is the protease responsible for the N-terminal cleavage of APP leading to the production of Aβ peptides and the development of BACE1 inhibitors as potential therapeutic agents for AD has generated tremendous interests from both academia and the pharmaceutical industry. A wide variety of BACE1 inhibitors have been reported, several of which have demonstrated highly promising efficacy in animal models of AD. This review focuses on recent disclosures of BACE1 inhibitors in the patent and scientific literature, covering the period from approximately May 2004 to November 2005.
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Keywords: Alzheimer's disease; BACE; aspartyl protease; drug discovery; inhibitors; β-secretase

Document Type: Research Article

Affiliations: Pharmacopeia Drug Discovery, Inc., Box 5350, Princeton, NJ 08543-5350, USA.

Publication date: 2006-06-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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