Design, Synthesis and Bioactivity of NYX-2925 L-Proline Derivatives as N-Methyl-D-aspartate (NMDA) Receptor Partial Agonists
文献类型：期刊论文
| 作者 | Wu Youjin3,4; Jin Zhengsheng3; Liu Yongjia1,3; Huang Wenqian1,2,3; Zhao Guilong1,2,3,4 |
| 刊名 | CHINESE JOURNAL OF ORGANIC CHEMISTRY
 |
| 出版日期 | 2024-04-01 |
| 卷号 | 44期号:4页码:1247-1263 |
| 关键词 | N-methyl-D-aspartate (NMDA) receptor partial agonist NYX-2925 synthesis bioactivity |
| ISSN号 | 0253-2786 |
| DOI | 10.6023/cjoc202310010 |
| 通讯作者 | Zhao Guilong(zhao_guilong@126.com) |
| 英文摘要 | N-Methyl-D-aspartate (NMDA) receptors belong to a family of ligand-gated ionotropic glutamate receptors and represent an important class of excitary receptors in central nervous system, which are critical for neuropathic pain, learning and memory. NYX-2925 is a lead compound of NMDA receptor partial agonist which is essentially a dipeptide mimetic with a novel spirocyclic beta-lactam functionality. In the present study, 10 novel derivatives of three different classes were designed based on NYX-2925 by a ring-opening strategy of the spirocyclic beta-lactam and synthesized. All these compounds were characterzied by H-1 NMR, C-13 NMR, F-19 NMR and high-resolution mass spectrometery (HRMS), and subjected to an in vitro assay of their effect on human NR1/NR2B NMDA receptor current determined by whole-cell manual patch-clamp technique. The preliminary results indicated that both NYX-2925 and the synthesized 10 compounds displayed no significant effects on NMDA receptor except (R)-N-((2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl)-2-benzyl-1-isobutyrylpyrrolidine-2-carboxamide (1g) displayed a moderate antagonistic effect, suggesting that the unique structure of NYX-2925 is not a preferred lead structure for the design of NMDA receptor partial agonists. The findings revealed in the present study should be valuable for the future design of NMDA receptor modulators based on the novel structure of dipeptide mimetic with a novel spirocyclic beta-lactam represented by NYX-2925. |
| WOS关键词 | NEUROPATHIC PAIN |
| 资助项目 | Zhongshan Municipal Natural Science Foundation[200805173640573] ; Zhongshan Municipal Natural Science Foundation[210730214049987] ; Guangdong Basic and Applied Basic Research Foundation[2021A1515010197] ; Guangdong Basic and Applied Basic Research Foundation[2023A1515012259] ; Creative Research Group of Zhongshan City[CXTD2022011] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001263874200014 |
| 出版者 | SCIENCE PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/312264]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhao Guilong |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Guangdong 528400, Peoples R China 4.Zunyi Med Univ, Sch Pharm, Zunyi 563003, Guizhou, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu Youjin,Jin Zhengsheng,Liu Yongjia,et al. Design, Synthesis and Bioactivity of NYX-2925 L-Proline Derivatives as N-Methyl-D-aspartate (NMDA) Receptor Partial Agonists[J]. CHINESE JOURNAL OF ORGANIC CHEMISTRY,2024,44(4):1247-1263. |
| APA | Wu Youjin,Jin Zhengsheng,Liu Yongjia,Huang Wenqian,&Zhao Guilong.(2024).Design, Synthesis and Bioactivity of NYX-2925 L-Proline Derivatives as N-Methyl-D-aspartate (NMDA) Receptor Partial Agonists.CHINESE JOURNAL OF ORGANIC CHEMISTRY,44(4),1247-1263. |
| MLA | Wu Youjin,et al."Design, Synthesis and Bioactivity of NYX-2925 L-Proline Derivatives as N-Methyl-D-aspartate (NMDA) Receptor Partial Agonists".CHINESE JOURNAL OF ORGANIC CHEMISTRY 44.4(2024):1247-1263. |
入库方式： OAI收割
来源：上海药物研究所
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