Liu Sijie, Shang Ruofeng, Shi Lanxiang, Wan David Chi-Cheong, Lin Huangquan
College of Chemical Engineering, Shijiazhuang University, 6 Changjiang Road, New Technology Development District, Shijiazhuang 050035, PR China.
Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, PR China, China.
Eur J Med Chem. 2014 Jun 23;81:237-44. doi: 10.1016/j.ejmech.2014.05.020. Epub 2014 May 9.
A series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives 7a-i were synthesized and evaluated as novel acetylcholinesterase (AChE) inhibitors. All target compounds were evaluated in vitro for the inhibitory activities against AChE via Ellman colorimetric assay. Compound 7c showed an excellent (89.82%) inhibitory activity. The molecular docking studies revealed that 7c, 7d and 7g, with the lateral chain in the para position of the phenyl ring, possessed an optimal docking pose and can perfectly fit into the catalytic active site (CAS) and peripheral anionic site (PAS), simultaneously, and, consequently, exhibited higher inhibitory potency than 7b that bears the same lateral chain as 7g, but in the ortho position of the phenyl ring.
合成了一系列7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮衍生物7a-i，并将其作为新型乙酰胆碱酯酶（AChE）抑制剂进行了评估。通过Ellman比色法在体外评估了所有目标化合物对AChE的抑制活性。化合物7c表现出优异的（89.82%）抑制活性。分子对接研究表明，苯环对位带有侧链的7c、7d和7g具有最佳的对接构象，能够同时完美地契合催化活性位点（CAS）和外周阴离子位点（PAS），因此，其抑制效力高于与7g具有相同侧链但位于苯环邻位的7b。
