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Synthesis, in vitro Biological Evaluation and Molecular Docking Studies of Benzimidamides as Potential BACE1 Inhibitors
Author(s) -
Niu Yan,
Gao Haifei,
Xu Fengrong,
Wang Chao,
Liu Peng,
Yang Guanyu,
Sun Qi,
Xu Ping
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12016
Subject(s) - in vitro , docking (animal) , chemistry , combinatorial chemistry , penetrant (biochemical) , stereochemistry , computational biology , biochemistry , biology , organic chemistry , medicine , nursing
A series of 3, 5‐disubstituted benzimidamides were synthesized and biologically evaluated as potential BACE1 inhibitors. Both the targeted compounds (benzimidamides) and the synthetic intermediates (benzonitriles) were tested for their BACE1 inhibitory activities in a cell‐free FRET assay. All the synthesized benzimidamides were active as BACE1 inhibitors and compound 6d showed the lowest IC 50 value of 3.35 μ m . Molecular docking study proposed a binding mode, which would help to the further optimization on 6d to achieve more potent, BBB penetrant BACE1 inhibitors.