Journal of Chinese Pharmaceutical Sciences ›› 2017, Vol. 26 ›› Issue (9): 650-659.DOI: 10.5246/jcps.2017.09.073

• Original articles • Previous Articles     Next Articles

Design and synthesis of 2-aminobenzimidazoles as potential BACE1 inhibitors

Jiapei Yu, Yan Niu*, Qi Sun, Fengrong Xu, Lei Liang, Chao Wang, Ping Xu*   

  1. Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2017-05-05 Revised:2017-06-18 Online:2017-09-30 Published:2017-07-29
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  • Supported by:
    National Natural Science Foundation of China (Grant No. 21002002/21172012).


Fragment-based drug discovery (FBDD) has been widely applied in the research of aspartyl protease inhibitors. In the present study, we reported our work on 2-aminobenzimidazole as the original fragment, which was predicted to bind with the catalytic aspartyl dyad (Asp228 and Asp32) of β-site amyloid precursor protein cleaving enzyme 1 (BACE1). A series of novel 2-aminobenzimidazole derivatives were designed and synthesized. The results from FRET assay revealed that three out of the 12 designed 2-aminobenzimidazoles could inhibit more than 50% of the enzymatic potency of BACE1 at 10 μM. Docking study showed that 2-aminobenzimidazole could form multiple hydrogen bonds and occupy S1/S2’ pockets well.

Key words: Alzheimer’s disease, BACE1 inhibitors, FBDD, 2-Aminobenzimidazole

CLC Number: