基于羟基亚乙基的β-分泌酶抑制剂的合成

基于羟基亚乙基的β-分泌酶抑制剂的合成

杨晓鸣, 邹晓民, 傅翌秋, 牟科, 徐萍^*

北京大学药学院药物化学系北京大学天然药物及仿生药物国家重点实验室, 北京 100083

收稿日期:2006-01-25 修回日期:2006-05-10 出版日期:2006-06-15 发布日期:2006-06-15
通讯作者: 徐萍*

Synthesis of Hydroxyethylene-based β-Secretase Inhibitors

YANG Xiao-ming, ZOU Xiao-min, FU Yi-qiu, MOU Ke, XU Ping^*

Department of Medicinal Chemistry, School of Pharmaceutical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083, China

Received:2006-01-25 Revised:2006-05-10 Online:2006-06-15 Published:2006-06-15
Contact: XU Ping*

摘要/Abstract

摘要： 目的深入探讨基于羟基亚乙基二肽的β-分泌酶抑制剂的合成方法。方法综合使用多种有机合成反应来合成拟肽类β-分泌酶抑制剂,包括亲核性加成反应、有机金属试剂协助的取代反应、催化氢化反应、传统多肽偶联反应等。结果以目标化合物之一化合物13作为模型物, 通过成功合成化合物13建立了反应条件优化的合成方法。结论本文建立的合成方法可用于构建β-分泌酶抑制剂化学库, 发现新的有效化合物。

关键词: β-分泌酶, β-分泌酶, β-分泌酶, 拟肽类, 拟肽类, 拟肽类, 羟乙基二肽电子等排体, 羟乙基二肽电子等排体, 羟乙基二肽电子等排体, 合成, 合成, 合成

Abstract: Aim To discuss in depth the synthesis of hydroxyethylene dipeptide-based β-secretase inhibitors; Methods Organic reactions such as nucleophilic addition and substitution assisted by organometallic agents, catalytic hydrogenation, and classic peptide coupling were used to synthesize peptidomimetic β-secretase inhibitors. Results Ideal reaction conditions and potential problems were investigated, and one of the designed β-secretase inhibitors 13 (as a model) was synthesized successfully; Conclusion This approach might be used to build up the β-secretase inhibitor library and to search for new molecular candidates.

Key words: β-secretase, β-secretase, peptidomimetics, peptidomimetics, hydroxyethylene dipeptide isostere, hydroxyethylene dipeptide isostere, synthesis, synthesis

中图分类号:

R916

Supporting:

Foundation item: National Natural Science Foundation of China (20272004 and 20572006) , and 985 Program, Ministry of Education of China.
^*Corresponding author. Tel.: 86-10-82801505; fax: 86-10-62015584

杨晓鸣, 邹晓民, 傅翌秋, 牟科, 徐萍^*. 基于羟基亚乙基的β-分泌酶抑制剂的合成[J]. .

YANG Xiao-ming, ZOU Xiao-min, FU Yi-qiu, MOU Ke, XU Ping^*. Synthesis of Hydroxyethylene-based β-Secretase Inhibitors[J]. .

参考文献

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