Current Medicinal Chemistry

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge


Progress in the Development of Nonpeptidomimetic BACE 1 Inhibitors for Alzheimers Disease

Author(s): Wen-Hai Huang, Rong Sheng and Yong-Zhou Hu

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


It is believed that the production and accumulation of beta-amyloid (Aβ) peptide is a critical step to the pathogenesis of Alzheimers 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.

Keywords: Alzheimer's disease (AD), nonpeptidomimetic inhibitors, BACE 1 inhibitor

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Article Details

Page: [1806 - 1820]
Pages: 15
DOI: 10.2174/092986709788186174