title: Synthesis, in vitro biological evaluation and molecular docking studies of benzimidamides as potential BACE1 inhibitors.
abstract: 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 μm. Molecular docking study proposed a binding mode, which would help to the further optimization on 6d to achieve more potent, BBB penetrant BACE1 inhibitors.
authors.forename: Yan
authors.initials: Y
authors.lastname: Niu
authors.forename: Haifei
authors.initials: H
authors.lastname: Gao
authors.forename: Fengrong
authors.initials: F
authors.lastname: Xu
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Guanyu
authors.initials: G
authors.lastname: Yang
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology*; D000578:Amidines / Q000737:chemistry* / Q000494:pharmacology*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship
chemical_list: D000578:Amidines; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human