(S)-4-(2-((3-(bis(2-(((S)-2-(6-methoxynaphthalen-2-yl)propanoyl)oxy)ethyl)amino)propanoyl)oxy)ethyl)-16-(6-methoxynaphthalen-2-yl)-11-(2-(((S)-2-(6-methoxynaphthalen-2-yl)propanoyl)oxy)ethyl)-8,15-dioxo-7,14-dioxa-4,11-diazaheptadecanoic acid | 1443752-30-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (S)-4-(2-((3-(bis(2-(((S)-2-(6-methoxynaphthalen-2-yl)propanoyl)oxy)ethyl)amino)propanoyl)oxy)ethyl)-16-(6-methoxynaphthalen-2-yl)-11-(2-(((S)-2-(6-methoxynaphthalen-2-yl)propanoyl)oxy)ethyl)-8,15-dioxo-7,14-dioxa-4,11-diazaheptadecanoic acid
• CAS: 1443752-30-4
• 化学式: C₇₇H₈₉N₃O₁₈
• 分子量: 1344.56
• InChiKey: VPCMRXFOCPGATO-GQYFIECQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.27
• 重原子数：
  98.0
• 可旋转键数：
  39.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  241.74
• 氢给体数：
  1.0
• 氢受体数：
  20.0

反应信息

• 作为反应物：
  描述：

  benzyl 3-(bis(2-hydroxyethyl)amino)propanoate 、 (S)-4-(2-((3-(bis(2-(((S)-2-(6-methoxynaphthalen-2-yl)propanoyl)oxy)ethyl)amino)propanoyl)oxy)ethyl)-16-(6-methoxynaphthalen-2-yl)-11-(2-(((S)-2-(6-methoxynaphthalen-2-yl)propanoyl)oxy)ethyl)-8,15-dioxo-7,14-dioxa-4,11-diazaheptadecanoic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以64.4%的产率得到
  参考文献：
  名称：

  Design, synthesis and biological evaluation of enzymatically cleavable NSAIDs prodrugs derived from self-immolative dendritic scaffolds for the treatment of inflammatory diseases

  摘要：

  It has been reported that delivery systems based on dendritic prodrugs of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) improved the properties of drug molecules and reduced the side effects and irritation on the gastric mucosa. To find a more effective way in NSAIDs dendritic prodrugs, in this paper, three different dendritic scaffolds of enzymatically cleavable naproxen conjugates have been synthesized in a convergent approach and well characterized by NMR and MS techniques. These self-immolative dendritic NISADs prodrugs programmed to release multiple molecules of the potent naproxen after a single enzymatic activation step, and in 50% human plasma, the drug released from the compound T3 reaching 47.3% after 24 h in vitro assay. Moreover, all prodrugs were also found to maintain more significant anti-inflammatory activity, no significant cytotoxicity against HEK293 cells and less degree of ulcerogenic potential in vivo than their monomeric counterpart naproxen. These results provided an effective entry to the development of new dendritic NSAIDs prodrugs. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.006
• 作为产物：
  描述：

  在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 (S)-4-(2-((3-(bis(2-(((S)-2-(6-methoxynaphthalen-2-yl)propanoyl)oxy)ethyl)amino)propanoyl)oxy)ethyl)-16-(6-methoxynaphthalen-2-yl)-11-(2-(((S)-2-(6-methoxynaphthalen-2-yl)propanoyl)oxy)ethyl)-8,15-dioxo-7,14-dioxa-4,11-diazaheptadecanoic acid
  参考文献：
  名称：

  Design, synthesis and biological evaluation of enzymatically cleavable NSAIDs prodrugs derived from self-immolative dendritic scaffolds for the treatment of inflammatory diseases

  摘要：

  It has been reported that delivery systems based on dendritic prodrugs of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) improved the properties of drug molecules and reduced the side effects and irritation on the gastric mucosa. To find a more effective way in NSAIDs dendritic prodrugs, in this paper, three different dendritic scaffolds of enzymatically cleavable naproxen conjugates have been synthesized in a convergent approach and well characterized by NMR and MS techniques. These self-immolative dendritic NISADs prodrugs programmed to release multiple molecules of the potent naproxen after a single enzymatic activation step, and in 50% human plasma, the drug released from the compound T3 reaching 47.3% after 24 h in vitro assay. Moreover, all prodrugs were also found to maintain more significant anti-inflammatory activity, no significant cytotoxicity against HEK293 cells and less degree of ulcerogenic potential in vivo than their monomeric counterpart naproxen. These results provided an effective entry to the development of new dendritic NSAIDs prodrugs. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.006

文献信息

• Novel naproxen-peptide-conjugated amphiphilic dendrimer self-assembly micelles for targeting drug delivery to osteosarcoma cells
  作者：Yinbo Zhao、Qi Zeng、Fengbo Wu、Jing Li、Zhaoping Pan、Pengfei Shen、Lu Yang、Ting Xu、Lulu Cai、Li Guo

  DOI：10.1039/c6ra15022e

  日期：——

  The aim of the current study was to synthesize and prepare novel self-assembly micelles loaded with curcumin (Cur) based on naproxen (Nap)-conjugated amphiphilic peptide dendrimers.

  本研究的目的是基于萘普瑞昔（Nap）共轭的两性肽树状分子合成和制备载有姜黄素（Cur）的新型自组装胶束。