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 |
| 文献子类 | Article |
| 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 |
| 语种 | 英语 |
| WOS记录号 | WOS:000238182500021 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273546]  |
| 专题 | 药物化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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