Synthesis and biological evaluation of 3,6-diaryl-7H-thiazolo[3,2-b] [1,2,4]triazin-7-one derivatives as acetylcholinesterase inhibitors.
Acetylcholinesterase (AChE) inhibitors played an important role in developing a cure for Alzheimer' s disease. In order to study on the influence of modifications at different groups and side chains on the AChE inhibitory ability and the active sites of 7H-thiazolo[3,2-b][1,2,4]triazin-7-one derivatives, fourteen 3,6-diaryl-7H-thiazolo[3,2-b][1,2,4]triazin-7-one derivatives were designed and synthesized. The study of AChE inhibitory activity was carried out using the Ellman colorimetric assay with huperzine-A as the positive control drug. Most of the target compounds exhibited more than 50% inhibition at 10 μM. Some target compounds showed strong inhibition against AChE. The molecular fields analysis and preliminary structure-activity relationships are discussed.
Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang, China.
Zhe
Z
Jin
Liu
L
Yang
Si-Jie
SJ
Liu
Jian
J
Wang
Shuo
S
Li
Huang-Quan
HQ
Lin
David Chi Cheong
DC
Wan
Chun
C
Hu
D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D030562:Databases, Protein; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry; D014101:Torpedo / Q000378:metabolism; D014227:Triazines / Q000737:chemistry
D002800:Cholinesterase Inhibitors; D058851:GPI-Linked Proteins; D013844:Thiazoles; D014227:Triazines; C548244:ACHE protein, human; D000110:Acetylcholinesterase