TY - JOUR T1 - Design, synthesis, and evaluation of 7H-thiazolo-[3,2-b]-1,2,4-triazin-7-one derivatives as dual binding site acetylcholinesterase inhibitors. AU - Liu,Sijie, AU - Shang,Ruofeng, AU - Shi,Lanxiang, AU - Zhou,Ran, AU - He,Jingyu, AU - Wan,David Chi-Cheong, Y1 - 2014/06/30/ PY - 2014/02/25/received PY - 2014/04/02/revised PY - 2014/04/30/accepted PY - 2014/6/4/entrez PY - 2014/6/4/pubmed PY - 2015/3/10/medline KW - 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives KW - Alzheimer's disease KW - acetylcholinesterase KW - docking KW - inhibitors KW - synthesis SP - 169 EP - 74 JF - Chemical biology & drug design JO - Chem Biol Drug Des VL - 84 IS - 2 N2 - New dual binding site acetylcholinesterase (AChE) inhibitors have been designed and synthesized as a new drug candidate for the treatment of Alzheimer's disease (AD) through the binding to both catalytic and peripheral sites of the enzyme. Therefore, a series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives 6a-j were synthesized and investigated for their ability to inhibit the activity of human AChE (hAChE) in comparison with huperzine-A. All the compounds were found to inhibit AChE activity, especially compounds 6c and 6i with the inhibition value of 76.10% and 77.82%, respectively. The molecular docking study indicated that they were nicely accommodated by AChE. The molecular docking study revealed that 6c and 6i possessed a more optimal binding conformation than 6a and can perfectly fit into the active and peripheral site of hAChE, and consequently exhibited highly improved inhibitor potency to hAChE. SN - 1747-0285 UR - https://www.unboundmedicine.com/medline/citation/24890706/Design_synthesis_and_evaluation_of_7H_thiazolo_[32_b]_124_triazin_7_one_derivatives_as_dual_binding_site_acetylcholinesterase_inhibitors_ DB - PRIME DP - Unbound Medicine ER -