Citation: Jia-Kuo Liu, Wei Gu, Xiao-Rui Cheng, Jun-Ping Cheng, Ai-Hua Nie, Wen-Xia Zhou. Design and synthesis of 5-cyclopropyl substituted cyclic acylguanidine compounds as BACE1 inhibitors[J]. Chinese Chemical Letters, ;2016, 27(10): 1626-1629. doi: 10.1016/j.cclet.2016.05.002 shu

Design and synthesis of 5-cyclopropyl substituted cyclic acylguanidine compounds as BACE1 inhibitors

Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China

Corresponding author: Ai-Hua Nie, ahnie512@163.com Wen-Xia Zhou, zhouwx@nic.bmi.ac.cn
Received Date: 1 March 2016
Revised Date: 6 April 2016
Accepted Date: 14 April 2016
Available Online: 11 October 2016

Figures(4)

By taking compound 1 as a lead, a series of 5-cyclopropyl substituted cyclic acylguanidine compounds were designed and synthesized as BACE1 inhibitors, compound 4d exhibited 84-fold improved inhibition efficiency than lead compound 1. The diphenyl fragment at the P3 position and the substituents at the second phenyl ring were essential for the compounds to achieve improved inhibition efficiency. This SAR studies provides new insights into the design and synthesis of more promising BACE1 inhibitors for the potential treatment of AD.
- Alzheimer's disease,
- BACE1 inhibitor,
- β-Secretase,
- Drug discovery,
- Cyclic acylguanidine
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沈阳化工大学材料科学与工程学院沈阳 110142