discoveryofpotentsecretasebace1inhibitorsbythesynthesisofisophthalamidecontaininghybrids

	discoveryofpotentsecretasebace1inhibitorsbythesynthesisofisophthalamidecontaininghybrids
	Yiping ZHU 1; Kun XIAO 1; Haiping YU 2; Lanping MA 1; Bing XIONG 1; Haiyan ZHANG 1; Xin WANG 1; Jingya LI 2; Jia LI 2; Jingkang SHEN 1
刊名	actapharmacologicasinica
	2009
卷号	030 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
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/288103]
专题	中国科学院上海药物研究所
作者单位	1.中国科学院上海药物研究所 2.The National Center for Drug Screening
推荐引用方式 GB/T 7714	Yiping ZHU,Kun XIAO,Haiping YU,et al. discoveryofpotentsecretasebace1inhibitorsbythesynthesisofisophthalamidecontaininghybrids[J]. actapharmacologicasinica,2009,030(002):259.
APA	Yiping ZHU.,Kun XIAO.,Haiping YU.,Lanping MA.,Bing XIONG.,...&Jingkang SHEN.(2009).discoveryofpotentsecretasebace1inhibitorsbythesynthesisofisophthalamidecontaininghybrids.actapharmacologicasinica,030(002),259.
MLA	Yiping ZHU,et al."discoveryofpotentsecretasebace1inhibitorsbythesynthesisofisophthalamidecontaininghybrids".actapharmacologicasinica 030.002(2009):259.