羟亚乙基拟肽类人β-分泌酶抑制剂的合成和活性

羟亚乙基拟肽类人β-分泌酶抑制剂的合成和活性

马超, 王月华, 杨晓鸣, 邹晓民, 吕杨, 杜冠华, 徐萍^*

1.北京大学药学院药物化学系, 北京 100191; 2. 中国医学科学院药物研究所, 北京 100050

收稿日期:2008-04-19 修回日期:2008-08-10 出版日期:2008-09-15 发布日期:2008-09-15
通讯作者: 徐萍*

Synthesis and activity of hydroxyethylene peptidomimetic inhibitors of human β-secretase

Chao Ma, Yue-Hua Wang, Xiao-Ming Yang, Xiao-Min Zou,Yang Lü, Guan-Hua Du, Ping Xu^*

1. Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China;
2. Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China

Received:2008-04-19 Revised:2008-08-10 Online:2008-09-15 Published:2008-09-15
Contact: Ping Xu*

摘要/Abstract

摘要：

本文设计并合成了一系列含Leu*Ala羟亚乙基二肽电子等排体的β-分泌酶拟肽类抑制剂, 并测定了β-分泌酶抑制活性。活性最强的化合物N9显示59.66% (10 mg/mL) 抑制率。化合物N9可经计算化学方法进一步优化。

关键词: β-分泌酶抑制剂, β-分泌酶抑制剂, β-分泌酶抑制剂, 羟亚乙基等排体, 羟亚乙基等排体, 羟亚乙基等排体, 合成, 合成, 合成, 生物活性, 生物活性, 生物活性, , ,

Abstract: A series of β-secretase peptidomimetic inhibitors with Leu*Ala hydroxyethylene dipeptide isostere were synthesized and their β-secretase inhibitory activities were measured. The most potent compound N9 showed an inhibitory rate of 59.66% (10 mg/mL). Compound N9 might be further modified by means of computational chemical methodology.

Key words: β-Secretase inhibitors, β-Secretase inhibitors, Hydroxyethylene isostere, Hydroxyethylene isostere, Synthesis, Synthesis, Bioactivity, Bioactivity

Supporting: Foundation items: National Natural Science Foundation of China (Grant No. 30772650 and 20772008).
^*Corresponding author. Tel.: 86-10-82801505; fax: 86-10-62015584

马超, 王月华, 杨晓鸣, 邹晓民, 吕杨, 杜冠华, 徐萍^*
. 羟亚乙基拟肽类人β-分泌酶抑制剂的合成和活性
[J]. .

Chao Ma, Yue-Hua Wang, Xiao-Ming Yang, Xiao-Min Zou,Yang Lü, Guan-Hua Du, Ping Xu^*. Synthesis and activity of hydroxyethylene peptidomimetic inhibitors of human β-secretase
[J]. .