8-甲氧基-4-氧代-1,4-二氢-1,5-萘啶-3-羧酸乙酯 | 64761-20-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 8-甲氧基-4-氧代-1,4-二氢-1,5-萘啶-3-羧酸乙酯
• 英文名称: Ethyl-8-methoxy-1,5-naphthyridin-4(1H)-on-3-carboxylat
• 英文别名: 8-methoxy-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic acid ethyl ester；Ethyl 8-methoxy-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylate；ethyl 8-methoxy-4-oxo-1H-1,5-naphthyridine-3-carboxylate
• CAS: 64761-20-2
• 化学式: C₁₂H₁₂N₂O₄
• 分子量: 248.238
• InChiKey: HUKDPUKPNGGPIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  8-甲氧基-4-氧代-1,4-二氢-1,5-萘啶-3-羧酸乙酯 在 喹啉 、 氢溴酸 、 三溴氧磷 作用下， 以 乙腈 为溶剂， 反应 6.0h， 生成 4,8-dibromo-1,5-naphthyridine
  参考文献：
  名称：

  Novel multifunctional organic semiconductor materials based on 4,8-substituted 1,5-naphthyridine: synthesis, single crystal structures, opto-electrical properties and quantum chemistry calculation

  摘要：

  一系列4,8取代的1,5-萘啶（1a–1h）已成功合成，通过4,8-二溴-1,5-萘啶（4）与相应的硼酸（2a–2h）在催化性醋酸钯的存在下进行铃木交叉偶联反应，收率为41.4%–75.8%，并得到良好表征。它们在热稳定性方面表现优异，具有高相变温度（高于186°C）。化合物1b、1e和1f分别在单斜晶系中结晶，空间群为P21/c、P21/c和P21/n。所有化合物表现出最低能量吸收带（λmaxAbs: 294–320 nm），揭示了较低的光学带隙（2.77–3.79 eV）。这些材料在二氯甲烷稀溶液中发出蓝色荧光，λmaxEm范围为434–521 nm，在固态中为400–501 nm。4,8取代的1,5-萘啶1a–1h的估计电子亲合能（EA）为2.38–2.72 eV，适合用作电子传输材料，而离子化势（IP）为4.85–5.04 eV，促进了优良的孔注入/孔传输材料特性。使用DFT B3LYP/6-31G*进行的量子化学计算显示，最低未占分子轨道（LUMO）几乎相同，范围为−2.39至−2.19 eV，最高占分子轨道（HOMO）范围为−5.33至−6.84 eV。这些结果表明，具有简单结构的4,8取代1,5-萘啶1a–1h可能是开发高效OLED的有希望的蓝色发射（或蓝绿色发射）材料、电子传输材料以及孔注入/孔传输材料。

  DOI：

  10.1039/c2ob25926e
• 作为产物：
  描述：

  4-羟基-3-硝基吡啶 在 palladium on activated charcoal 、 氢气 、 potassium carbonate 作用下， 以 甲醇 、 二苯醚 、 乙醇 、 丙酮 为溶剂， 40.0~100.0 ℃ 、482.64 kPa 条件下， 反应 3.42h， 生成 8-甲氧基-4-氧代-1,4-二氢-1,5-萘啶-3-羧酸乙酯
  参考文献：
  名称：

  Second generation of diazachrysenes: Protection of Ebola virus infected mice and mechanism of action

  摘要：

  Ebola virus (EBOV) causes a deadly hemorrhagic fever in humans and non-human primates. There is currently no FDA-approved vaccine or medication to counter this disease. Here, we report on the design, synthesis and anti-viral activities of two classes of compounds which show high potency against EBOV in both in vitro cell culture assays and in vivo mouse models Ebola viral disease. These compounds incorporate the structural features of cationic amphiphilic drugs (CAD), i.e they possess both a hydrophobic domain and a hydrophilic domain consisting of an ionizable amine functional group. These structural features enable easily diffusion into cells but once inside an acidic compartment their amine groups became protonated, ionized and remain trapped inside the acidic compartments such as late endosomes and lysosomes. These compounds, by virtue of their lysomotrophic functions, blocked EBOV entry. However, unlike other drugs containing a CAD moiety including chloroquine and amodiaquine, compounds reported in this study display faster kinetics of accumulation in the lysosomes, robust expansion of late endosome/lysosomes, relatively more potent suppression of lysosome fusion with other vesicular compartments and inhibition of cathepsins activities, all of which play a vital role in anti-EBOV activity. Furthermore, the diazachrysene 2 (ZSML08) that showed most potent activity against EBOV in in vitro cell culture assays also showed significant survival benefit with 100% protection in mouse models of Ebola virus disease, at a low dose of 10 mg/kg/day. Lastly, toxicity studies in vivo using zebrafish models suggest no developmental defects or toxicity associated with these compounds. Overall, these studies describe two new pharmacophores that by virtue of being potent lysosomotrophs, display potent anti-EBOV activities both in vitro and in vivo animal models of EBOV disease. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.10.061

文献信息

• [EN] NEUROLOGICALLY-ACTIVE COMPOUNDS<br/>[FR] COMPOSÉS NEUROLOGIQUEMENT ACTIFS
  申请人：PRANA BIOTECHNOLOGY LTD

  公开号：WO2004031161A1

  公开（公告）日：2004-04-15

  The present invention relates to neurologically-active compounds, being heterocyclic compounds having two fused 6-membered rings with a nitrogen atom at position 1 and a hydroxy or mercapto group at position 8 with at least one ring being aromatic. Also disclosed are processes for the preparation of these compounds and their use as pharmaceutical or veterinary agents, in particular for the treatment of neurological conditions, more specifically neurodegenerative conditions such as Alzheimer's disease.

  本发明涉及具有两个融合的6元环，其中第1位置有一个氮原子，第8位置有一个羟基或巯基基团的神经活性化合物，其中至少一个环是芳香环。还公开了制备这些化合物的方法以及它们作为药物或兽药剂的用途，特别是用于治疗神经系统疾病，更具体地说是神经退行性疾病，如阿尔茨海默病。
• NEUROLOGICALLY ACTIVE COMPOUNDS
  申请人：Barnham Kevin Jeffrey

  公开号：US20100160346A1

  公开（公告）日：2010-06-24

  The present invention relates to neurologically-active compounds, processes for their preparation and their use as pharmaceutical or veterinary agents, in particular for the treatment of neurological conditions, more specifically neurodegenerative conditions such as Alzheimer's disease.

  本发明涉及神经活性化合物，其制备方法以及它们作为制药或兽医制剂的用途，特别是用于治疗神经系统疾病，更具体地说是神经退行性疾病，如阿尔茨海默病。
• BROWN S. B.; DEWAR M. J. S., J. ORG. CHEM. 1978, 43, NO 7, 1331-1337
  作者：BROWN S. B.、 DEWAR M. J. S.

  DOI：——

  日期：——
• US7692011B2
  申请人：——

  公开号：US7692011B2

  公开（公告）日：2010-04-06