Design, synthesis and evaluation of galanthamine derivatives as acetylcholinesterase inhibitors.
A new series of galanthamine derivatives have been designed, synthesized and evaluated as acetylcholinesterase inhibitors. All of the new compounds prepared showed high AChE inhibitory activities, with compound 3e that has an N-hexyl-benzyl piperidine substituent on the nitrogen atom reaching the best inhibitory activity for AChE (IC(50)=5.62 nM). The docking study performed with AutoDock demonstrated that 3e was nicely accommodated by AChE.
Jia
Ping
P
ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Sheng
Rong
R
Zhang
Jing
J
Fang
Liang
L
He
Qiaojun
Q
Yang
Bo
B
Hu
Yongzhou
Y
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis*; D003198:Computer Simulation; D015195:Drug Design; D005702:Galantamine / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D010880:Piperidines; D011485:Protein Binding; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D010880:Piperidines; D005702:Galantamine