Efficient synthesis and reaction pathway studies of novel fused morpholine oxadiazolines for use as gamma secretase modulators
Efficient synthesis and reaction pathway studies of novel fused morpholine oxadiazolines for use as gamma secretase modulators
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DOI：
10.1016/j.tetlet.2012.09.070
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发表时间：
2012-11-21
影响因子：
1.8
通讯作者：
Buevich, Alexei
中科院分区：
文献类型：
--
作者：
Huang, Xianhai;Pissarnitski, Dmitri;Buevich, Alexei
为了确定治疗阿尔茨海默病的最佳γ分泌酶调节剂先导化合物，完成了融合吗啉恶二唑啉核心结构的有效合成。为关键的分子内环化反应提出了反应途径，并设计了化学来探索这些假设。实现了强效 GSM 27 的高度非对映选择性合成。为了进一步改进合成，开发了第二条路线，成功解决了稠合七元环副产物的形成，并为加速未来的 SAR 研究提供了机会。 (C) 2012 Elsevier Ltd. 保留所有权利。
An efficient synthesis of fused morpholine oxadiazoline core structures was accomplished in an effort to identify optimum gamma secretase modulator leads in the treatment of Alzheimer's disease. Reaction pathways were proposed for the key intramolecular cyclization reaction, and chemistry was designed to probe these hypotheses. A highly diastereoselective synthesis of potent GSM 27 was achieved. To further improve the synthesis, a second route was developed which successfully addressed the formation of a fused seven-member ring by-product, and provided opportunities to accelerate future SAR studies. (C) 2012 Elsevier Ltd. All rights reserved.