Synthesis and biological evaluation of 3,6-diaryl-7H-thiazolo[3,2-b] [1,2,4]triazin-7-one derivatives as acetylcholinesterase inhibitors

• Published in: Archives of pharmacal research 2010, 33(10), , pp.1641-1649
• Main Authors: Jin, Zhe, Yang, Liu, Liu, Si-Jie, Wang, Jian, Li, Shuo, Lin, Huang-Quan, Wan, David Chi Cheong, Hu, Chun
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase - chemistry; Acetylcholinesterase - metabolism; Alzheimer Disease - drug therapy; Animals; Binding Sites; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - metabolism; Cholinesterase Inhibitors - pharmacology; Databases, Protein; GPI-Linked Proteins - antagonists & inhibitors; GPI-Linked Proteins - chemistry; GPI-Linked Proteins - metabolism; Humans; Magnetic Resonance Spectroscopy; Medicine; Models, Molecular; Molecular Conformation; Pharmacology/Toxicology; Pharmacy; Protein Binding; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Infrared; Structure-Activity Relationship; Thiazoles - chemistry; Torpedo - metabolism; Triazines - chemistry; 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-010-1013-8

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 7 H -thiazolo[3,2- b ][1,2,4]triazin-7-one derivatives, fourteen 3,6-diaryl-7 H -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 structureactivity relationships are discussed.