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Progress in the Development of Nonpeptidomimetic BACE 1 Inhibitors for Alzheimer's Disease

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It is believed that the production and accumulation of beta-amyloid (Aβ) peptide is a critical step to the pathogenesis of Alzheimer's disease (AD). BACE 1 (beta-site APP-cleaving enzyme 1 or β-secretase), the key enzyme required for generating Aα from the β-amyloid precursor protein (APP), is regarded as an ideal target for AD therapeutic drug design. Due to low oral bioavailability, metabolic instability and poor ability to penetrate the central nervous system (CNS) of the existing peptidomimetic inhibitors, researchers have paid more attention to the development of nonpeptidomimetic inhibitors in recent years. A number of drug screening approaches and technologies have been used to identify novel nonpeptidomimetic BACE 1 inhibitors. This review mainly focuses on the recent developments in structure-based design and synthesis of the nonpeptidomimetic BACE 1 inhibitors.
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Keywords: Alzheimer's disease (AD); BACE 1 inhibitor; nonpeptidomimetic inhibitors

Document Type: Research Article

Affiliations: ZJU-ENS joint laboratory of medicinal chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Publication date: 2009-05-01

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