Department of Pharmaceutical Sciences, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
Bioorg Med Chem. 2010 Nov 15;18(22):7991-6. doi: 10.1016/j.bmc.2010.09.032. Epub 2010 Sep 18.
β-Secretase (BACE1) has been widely recognized as one of the possible therapeutic targets for the treatment of Alzheimer's disease. In this paper, we report the synthesis and the BACE1 inhibitory activity of new, variously substituted N-(3-(4-benzhydrylpiperazin-1-yl)-2-hydroxypropyl) arylsulfonamides. Each enantiomeric form was separately evaluated in BACE1 inhibition assays and IC(50) values were obtained in the low micromolar range. According to our biological results and docking studies, it can be asserted that the stereochemistry around the OH group in the central hydroxyethylamino linker does not significantly influence the BACE1 inhibitory activity of this type of molecules.
β-分泌酶（BACE1）已被广泛认为是治疗阿尔茨海默病的可能治疗靶点之一。在本文中，我们报告了新型、各种取代的 N-(3-(4-苯并二氢吡咯-1-基)-2-羟丙基)芳基磺酰胺的合成和 BACE1 抑制活性。每个对映异构体都分别在 BACE1 抑制测定中进行了评估，并获得了低微摩尔范围内的 IC50 值。根据我们的生物学结果和对接研究，可以断言，在中央羟乙基氨基连接子中的 OH 基团周围的立体化学结构不会显著影响此类分子的 BACE1 抑制活性。
