Department of Medicinal Chemistry, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Department of Medicinal Chemistry, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Eur J Med Chem. 2016 Nov 29;124:36-48. doi: 10.1016/j.ejmech.2016.08.024. Epub 2016 Aug 13.
The design, synthesis, SAR, and biological profile of a substituted 4-morpholine sulfonamide series of γ-secretase inhibitors (GSIs) were described. In several cases, the resulting series of GSIs reduced CYP liabilities and improved γ-secretase inhibition activity compared to our previous research series. Selected compounds demonstrated significant reduction of amyloid-β (Aβ) after acute oral dosing in a transgenic animal model of Alzheimer's disease (AD).
描述了一系列取代的 4-吗啉磺酰胺γ-分泌酶抑制剂（GSIs）的设计、合成、SAR 和生物学特征。在几种情况下，与我们之前的研究系列相比，所得的 GSI 系列降低了 CYP 的负担并提高了 γ-分泌酶抑制活性。在阿尔茨海默病（AD）的转基因动物模型中，选定的化合物在急性口服给药后显著减少了淀粉样蛋白-β（Aβ）的产生。
