Design, Synthesis and In Vitro Biological Evaluation of 3- styrylbenzimidamides as Potential BACE1 Inhibitors

Title:Design, Synthesis and In Vitro Biological Evaluation of 3- styrylbenzimidamides as Potential BACE1 Inhibitors

Volume: 10 Issue: 4

Author(s): Yan Niu, Haifei Gao, Fengrong Xu, Lei Liang, Peng Liu, Chao Wang, Guanyu Yang, Qi Sun and Ping Xu

Affiliation:

Keywords: Alzheimer’s disease, BACE1 inhibitors, 3-styrylbenzimidamide, CADD

Abstract: A series of 3-styrylbenzimidamides were synthesized and biologically evaluated in a cell free FRET assay as potential BACE1 inhibitors. Some of the synthesized analogues were discovered to have moderate BACE1 inhibitory activities with IC50 values ranging from 9.3 to 295.8 μM. Molecular docking study proposed that the most potent compound (E)-2d bound to BACE1 differently in S3-S2’ subpockets forming no polar interaction with the catalytic Asp dyad compared with the 3-styrylbenzimidamides. The results would contribute to the further optimizations on benzimidamide scaffold to achieve novel small molecular BACE1 inhibitors with improved potencies.

Cite this article as:

Niu Yan, Gao Haifei, Xu Fengrong, Liang Lei, Liu Peng, Wang Chao, Yang Guanyu, Sun Qi and Xu Ping, Design, Synthesis and In Vitro Biological Evaluation of 3- styrylbenzimidamides as Potential BACE1 Inhibitors, Letters in Drug Design & Discovery 2013; 10 (4) . https://dx.doi.org/10.2174/1570180811310040003