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Design, synthesis, biological evaluation, and docking study of 4‐isochromanone hybrids bearing N ‐benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II )
Author(s) -
Wang Jia,
Wang Chaolei,
Wu Zheng,
Li Xinnan,
Xu Shengtao,
Liu Jie,
Lan Qinying,
Zhu Zheying,
Xu Jinyi
Publication year - 2018
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.13136
Subject(s) - moiety , acetylcholinesterase , pyridinium , chemistry , stereochemistry , aché , docking (animal) , ic50 , selectivity , enzyme , combinatorial chemistry , biochemistry , in vitro , organic chemistry , medicine , nursing , catalysis
A series of novel 4‐isochromanone compounds bearing N ‐benzyl pyridinium moiety were designed and synthesized as acetylcholinesterase ( AC hE) inhibitors. The biological evaluation showed that most of the target compounds exhibited potent inhibitory activities against AC hE. Among them, compound 1q possessed the strongest anti‐ AC hE activity with an IC 50 value of 0.15 n m and high AC hE/BuChE selectivity ( SI > 5,000). Moreover, compound 1q had low toxicity in normal nerve cells and was relatively stable in rat plasma. Together, the current finding may provide a new approach for the discovery of novel anti‐Alzheimer's disease agents.