3-((diethylamino)methyl)-4-hydroxybenzaldehyde

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-((diethylamino)methyl)-4-hydroxybenzaldehyde
• 英文别名: 3-(Diethylaminomethyl)-4-hydroxybenzaldehyde
• 化学式: C₁₂H₁₇NO₂
• 分子量: 207.272
• InChiKey: WTRUVRCKAUTZTO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-((diethylamino)methyl)-4-hydroxybenzaldehyde 以 乙醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 (Z)-N’-((E)-3,5-bis((diethylamino)methyl)-4-hydroxybenzylidene)-3-hydroxy-3-(phenanthrene-9-yl)propanehydrazonamide
  参考文献：
  名称：

  3-Hydroxy-N′-arylidenepropanehydrazonamides with Halo-Substituted Phenanthrene Scaffolds Cure P. berghei Infected Mice When Administered Perorally

  摘要：

  Structural optimization of 3-hydroxy-N'-arylidenepropanehydrazonamides provided new analogs with nanomolar to subnanomolar antiplasmodial activity against asexual blood stages of Plasmodium falciparum, excellent parasite selectivity, and nanomolar activity against the earliest forms of gametocyte development. Particularly, derivatives with a 1,3-dihalo-6-trifluoromethylphenanthrene moiety showed outstanding in vivo properties and demonstrated in part curative activity in the Plasmodium berghei mouse model when administered perorally.

  DOI：

  10.1021/acs.jmedchem.7b00140
• 作为产物：
  描述：

  聚合甲醛 、 对羟基苯甲醛 、 二乙胺 在 盐酸 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 生成 3-((diethylamino)methyl)-4-hydroxybenzaldehyde
  参考文献：
  名称：

  具有肿瘤选择性毒性的新型不对称 3,5-双（亚苄基）-4-哌啶酮

  摘要：

  两个系列的新型不对称 3,5-bis(benzylidene)-4 哌啶酮2a – f和3a – e被设计为候选抗肿瘤药物。这些化合物对两种结肠癌以及几种口腔鳞状细胞癌显示出强大的细胞毒性。这些化合物对各种非恶性细胞的毒性较小，从而产生较大的选择性指数 (SI) 数据。许多化合物对 CEM 淋巴瘤和 HL-60 白血病细胞也具有细胞毒性。代表性化合物诱导凋亡细胞死亡，其特征是在一些 OSCC 细胞中 caspase-3 激活和 subG1 积累，以及 CEM 细胞中线粒体膜电位的去极化。进一步的调查旨在发现 SI 值是否与烯烃碳原子上的原子电荷相关。ADME（吸收、分布、代谢、

  DOI：

  10.3390/molecules27196718

文献信息

• Novel 3-benzylidene/benzylphthalide Mannich base derivatives as potential multifunctional agents for the treatment of Alzheimer’s disease
  作者：Zhongcheng Cao、Qing Song、Guangjun Yu、Zhuoling Liu、Shiqing Cong、Zhenghuai Tan、Yong Deng

  DOI：10.1016/j.bmc.2021.116074

  日期：2021.4

  Alzheimer’s disease, a series of 3-benzylidene/benzylphthalide Mannich base derivatives were designed, synthesized and evaluated. The biological screening results indicated that most of these derivatives exhibited good multifunctional activities. Among them, compound (Z)-13c raised particular interest because of its excellent multifunctional bioactivities. It displayed excellent EeAChE and HuAChE inhibition

  为了发现治疗阿尔茨海默病的新型多功能药物，设计、合成和评估了一系列 3-亚苄基/苄基苯酞曼尼希碱衍生物。生物筛选结果表明，这些衍生物大多表现出良好的多功能活性。其中，化合物( Z )-13c因其优异的多功能生物活性而引起了人们的特别关注。它显示出优异的Ee AChE 和Hu AChE 抑制（IC 50  = 9.18 × 10 -5和 6.16 × 10 -4 μM，分别），良好的 MAO-B 抑制活性（IC 50 = 5.88 μM）和高抗氧化活性（ORAC = 2.05 Trolox 当量）。此外，它还表现出良好的抗血小板聚集活性、中等的自身和Cu 2+诱导的A β 1-42聚集抑制效力、对A β 1-42原纤维的解聚能力、生物金属螯合能力、适当的BBB渗透性和显着的神经保护作用。此外，( Z )-13c还可以改善东莨菪碱诱导的小鼠学习记忆障碍。这些多功能特性突出了化合物( Z )-13c作为进一步开发抗
• 2-取代甲基-4-取代氨基甲基苯酚类衍生物及其医药用途
  申请人：中国人民解放军军事科学院军事医学研究院

  公开号：CN109503488A

  公开（公告）日：2019-03-22

  本发明涉及式(I)所示的一类2‑取代甲基‑4‑取代氨基甲基苯酚衍生物及其在药物学上可接受的盐、异构体、前药和药物组合物，此类化合物可重活化有机磷毒剂抑制的乙酰胆碱酯酶，其中R1为(对位取代基R1为酰胺，取代酰胺，取代氨基，甲酸甲酯或甲酸乙酯)，R2为咪唑，吡咯，哌啶，哌嗪，N甲基哌嗪或C1～C3双取代的氨基。本发明还公开了所述化合物的制各及其作为药物的应用，特别是作为有机磷毒剂中毒解毒药物及作为治疗阿尔兹海默症药物的应用。
• Discovery of Novel Non-Oxime Reactivators Showing In Vivo Antidotal Efficiency for Sarin Poisoned Mice
  作者：Zhao Wei、Xinlei Zhang、Huifang Nie、Lin Yao、Yanqin Liu、Zhibing Zheng、Qin Ouyang

  DOI：10.3390/molecules27031096

  日期：——

  inhibited human acetylcholinesterase was discovered. It was found that aromatic groups coupled to Mannich phenols and the introduction of imidazole to the ortho position of phenols would dramatically enhance reactivation efficiency. Moreover, the in vivo experiment was conducted, and the results demonstrated that Mannich phenol L10R1 (30 mg/kg, ip) could afford 100% 48 h survival for mice of 2*LD50

  一类新型高效非肟化合物对 VX 表现出有希望的再激活功效，并且发现了沙林抑制的人乙酰胆碱酯酶。发现与曼尼希酚偶联的芳香基团和在酚的邻位引入咪唑会显着提高再活化效率。此外，进行了体内实验，结果表明，曼尼希酚 L10R1 (30 mg/kg, ip) 可以为 2*LD50 沙林暴露的小鼠提供 100% 的 48 h 存活率，这对于开发非具有中心效率的肟再活化剂。
• Novel in vivo active anti-malarials based on a hydroxy-ethyl-amine scaffold
  作者：Claire-Lise Ciana、Romain Siegrist、Hamed Aissaoui、Léo Marx、Sophie Racine、Solange Meyer、Christoph Binkert、Ruben de Kanter、Christoph Fischli、Sergio Wittlin、Christoph Boss

  DOI：10.1016/j.bmcl.2012.11.118

  日期：2013.2

  A novel series of anti-malarials, based on a hydroxy-ethyl-amine scaffold, initially identified as peptidomimetic protease inhibitors is described. Combination of the hydroxy-ethyl-amine anti-malarial phramacophore with the known Mannich base pharmacophore of amodiaquine (57) resulted in promising in vivo active novel derivatives. (c) 2012 Elsevier Ltd. All rights reserved.
• Synthesis and in Vitro Anticancer Activity of the First Class of Dual Inhibitors of REV-ERBβ and Autophagy
  作者：Esther Torrente、Chiara Parodi、Luisa Ercolani、Claudia De Mei、Alessio Ferrari、Rita Scarpelli、Benedetto Grimaldi

  DOI：10.1021/acs.jmedchem.5b00511

  日期：2015.8.13

  Autophagy inhibition is emerging as a promising anticancer strategy. We recently reported that the circadian nuclear receptor REV-ERB beta plays an unexpected role in sustaining cancer cell survival when the autophagy flux is compromised. We also identified 4-[[[1-(2-fluorophenyl)cyclopentynamino]methyl]-2-[(4-methylpiperazin-1-yl)methyl]phenol, 1 (ARN5187), as a novel dual inhibitor of REV-ERB beta and autophagy. 1 had improved cytotoxicity against BT-474 breast cancer cells compared to chloroquine, a clinically relevant autophagy inhibitor. Here, we present the results of structure activity studies, based around 1, that disclose the first class of dual inhibitors of REV-ERB beta and autophagy. This study led to identification of 18 and 28, which were more effective REV-ERB beta antagonists than 1 and were more cytotoxic to BT-474. The combination of optimal chemical and structural moieties of these analogs generated 30, which elicited 15-fold greater REV-ERB beta inhibitory and cytotoxic activities compared to 1. Furthermore, 30 induced death in a panel of tumor cell lines at doses 5-50 times lower than an equitoxic amount of chloroquine but did not affect the viability of normal mammary epithelial cells.