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Structure-based design of hexahydropyrimidin-5-ols as novel non-peptidic β-secretase inhibitors

Bo Zhou, Yan Niu, Xiao-Min Zou, Feng-Rong Xu, Yue Yuan, Chao Wang, Hai-Fei Gao, Peng Liu, Ping Xu*   

  1. Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2010-05-25 Revised:2010-08-10 Online:2010-09-20 Published:2010-09-20
  • Contact: Ping Xu*

Abstract:

Based upon the crystal structure of a previously reported fragment hit that binds to β-secretase, a novel series of non-peptidic small-molecule β-secretase inhibitors, namely hexahydropyrimidin-5-ols, along with two series of their analogues, were rationally designed through structural modification. The CADD study was performed and revealed good expectation. Inhibitory activities of the corresponding structural cores were tested, which provided further support for our design approach.

Key words: β-Secretase inhibitors, Hexahydropyrimidin-5-ols, Structure-based drug design, Computer-aided drug design

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