Design, synthesis, and evaluation of leu*ala hydroxyethylene-based non-peptide beta-secretase (bace) inhibitors
文献类型：期刊论文
| 作者 | Xiao, K; Li, X; Li, JY; Ma, LP; Hu, B; Yu, HP; Fu, Y; Wang, R; Ma, ZQ; Qiu, BY |
| 刊名 | Bioorganic & medicinal chemistry
 |
| 出版日期 | 2006-07-01 |
| 卷号 | 14期号:13页码:4535-4551 |
| 关键词 | Bace Non-peptide inhibitor Combinatorial synthesis Hydrogen bond |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2006.02.024 |
| 通讯作者 | Wang, r() |
| 英文摘要 | With the aim of developing small molecular non-peptide p-secretase (bace) inhibitors, leu*ala hydroxyethylene (he) was investigated as a scaffold to design and synthesize a series of compounds. taking advantage of efficient combinatorial synthesis approaches and molecular modeling, extensive structure-activity relationship (sar) studies were carried out on the n- and c-terminal residues of the leu*ala he scaffold. isobutyl amine was found to be an optimal c-cap, and suitable hydroxylalkylamines at the 3-position and nitro or methyl(methylsulfonyl)amine at the 5-position of isophthalamide as the n-terminus could form additional hydrogen bonds with bace active sites and help improve potency. many new potent non-peptide bace inhibitors were identified in this study. among them, compounds 37 and 44 exhibited excellent enzyme-inhibiting potency, comparable to that of om99-2, and obvious inhibitory effects in cell-based assay with low molecular weights (< 600). (c) 2006 elsevier ltd. all rights reserved. |
| WOS关键词 | HUMAN BRAIN ; PROTEASE INHIBITORS ; ALZHEIMERS-DISEASE ; POTENT INHIBITORS ; GENERATION ; PEPTIDES ; ISOSTERE ; DRUGS |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| WOS类目 | Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Chemistry, Organic |
| 语种 | 英语 |
| WOS记录号 | WOS:000238182500021 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2379742 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Wang, R |
| 作者单位 | 1.Chinese Acad Sci, Grad Sch, State Key Lab Drug Res, Shanghai Inst Mat Med,Shanghai Inst Biol Sci, Shanghai 201203, Peoples R China 2.Natl Ctr Drug Screening, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xiao, K,Li, X,Li, JY,et al. Design, synthesis, and evaluation of leu*ala hydroxyethylene-based non-peptide beta-secretase (bace) inhibitors[J]. Bioorganic & medicinal chemistry,2006,14(13):4535-4551. |
| APA | Xiao, K.,Li, X.,Li, JY.,Ma, LP.,Hu, B.,...&Shen, JK.(2006).Design, synthesis, and evaluation of leu*ala hydroxyethylene-based non-peptide beta-secretase (bace) inhibitors.Bioorganic & medicinal chemistry,14(13),4535-4551. |
| MLA | Xiao, K,et al."Design, synthesis, and evaluation of leu*ala hydroxyethylene-based non-peptide beta-secretase (bace) inhibitors".Bioorganic & medicinal chemistry 14.13(2006):4535-4551. |
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来源：中国科学院大学
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