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Design and synthesis of benzimidamides as potential BACE1 inhibitors

Hai-Fei Gao, Yan Niu*, Feng-Rong Xu, Lei Liang, Bo Zhou, Yong-Jian Li, Chao Wang, Peng Liu, Ping Xu*   

  1. Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2011-05-26 Revised:2011-10-20 Online:2012-03-15 Published:2012-03-15
  • Contact: Yan Niu*, Ping Xu*


Computer aided fragment-based lead discovery has been successfully applied to the design of inhibitors of aspartyl protease enzyme β-secretase (BACE1). A benzimidamide fragment, which binds to the two catalytic aspartic acid residues in the active site of the enzyme, was selected as the starting compound. A novel series of 3-phenethylbenzimidamide inhibitors were designed and synthesized. Although biological evaluation results showed that the compounds displayed poor inhibitory activity towards BACE1, 3-phenethylbenzimidamide analogs might be modified as potential BACE1 inhibitors.

Key words: Alzheimer's disease, BACE1 inhibitors, CADD, Benzimidamide

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