Discovery of potent β-secretase （bace-1） inhibitors by the synthesis of isophthalamide-containing hybrids
文献类型：期刊论文
| 作者 | Yiping ZHU2; Kun XIAO2; Haiping YU1; Lanping MA2 ; Bing XIONG2; Haiyan ZHANG2; Xin WANG2; Jingya LI1; Jia LI1; Jingkang SHEN2
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| 刊名 | 中国药理学报：英文版
 |
| 出版日期 | 2009 |
| 卷号 | 30.0期号:002页码:259 |
| 关键词 | 蛋白酶 抑制剂 生物进化 分子模型 |
| ISSN号 | 1671-4083 |
| 英文摘要 | Aim： The aim of this study was to design and synthesize a series of high activity compounds against aspartyl protease β-secretase （BACE-1） bearing hydroxyethylene （HE） framework. Methods： First, we designed the small library based on our previous work and rational analysis. Subsequently, thirteen compounds were selected and synthesized using skilled solid phase synthetic methods to explore the relationship between structure and activity. We then used molecular modeling to explain the possible binding mode. Results： Thirteen new compounds （6-18） have been designed, synthesized and bioassayed. Their structures were determined by nuclear magnetic resonance （NMR） spectra, low-and high-resolution mass spectra and optical rotation. Most compounds have shown moderate to excellent activities, and compound 10, which contains fewer amino acids and amide bonds than GRL-7234, was about 5-fold more potent than the control compound 4 discovered by Merck. The molecular modeling results have indicated the possible binding mode and explained the difference between compounds 10 and 16, providing direction for further study. Conclusion： This study yielded several high activity compounds bearing fewer amino acids and amide bonds than previous compounds, providing insight into the further development of potent BACE-1 inhibitors for the treatment of Alzheimer＇s disease. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/294024]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.The National Center for Drug Screening 2.中国科学院上海药物研究所 |
| 推荐引用方式 GB/T 7714 | Yiping ZHU,Kun XIAO,Haiping YU,等. Discovery of potent β-secretase （bace-1） inhibitors by the synthesis of isophthalamide-containing hybrids[J]. 中国药理学报：英文版,2009,30.0(002):259. |
| APA | Yiping ZHU.,Kun XIAO.,Haiping YU.,Lanping MA.,Bing XIONG.,...&Jingkang SHEN.(2009).Discovery of potent β-secretase （bace-1） inhibitors by the synthesis of isophthalamide-containing hybrids.中国药理学报：英文版,30.0(002),259. |
| MLA | Yiping ZHU,et al."Discovery of potent β-secretase （bace-1） inhibitors by the synthesis of isophthalamide-containing hybrids".中国药理学报：英文版 30.0.002(2009):259. |
入库方式： OAI收割
来源：上海药物研究所
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