4-hydroxy-3-[(4-methylpiperazin-1-yl)methyl]benzaldehyde

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-hydroxy-3-[(4-methylpiperazin-1-yl)methyl]benzaldehyde
• 英文别名: 4-Formyl-2-[(4-methylpiperazin-1-ium-1-yl)methyl]phenolate
• 化学式: C₁₃H₁₈N₂O₂
• 分子量: 234.298
• InChiKey: RSGCVVRIRVIRDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-hydroxy-3-[(4-methylpiperazin-1-yl)methyl]benzaldehyde 在 盐酸 、 三乙酰氧基硼氢化钠 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 生成 4-[[[1-(2-fluorophenyl)-1-methylethyl]amino]methyl]-2-[(4-methylpiperazin-1-yl)methyl]phenol trihydrochloride
  参考文献：
  名称：

  Synthesis and in Vitro Anticancer Activity of the First Class of Dual Inhibitors of REV-ERBβ and Autophagy

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.5b00511
• 作为产物：
  描述：

  N-甲基哌嗪 、 聚合甲醛 、 对羟基苯甲醛 在 盐酸 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 生成 4-hydroxy-3-[(4-methylpiperazin-1-yl)methyl]benzaldehyde
  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

• [EN] DIARYLALKYLAMINE REV-ERB ANTAGONISTS AND THEIR USE AS MEDICAMENTS<br/>[FR] ANTAGONISTES DIARYLALKYLAMINES DE REV-ERB ET LEUR UTILISATION COMME MÉDICAMENTS
  申请人：FOND ISTITUTO ITALIANO DI TECNOLOGIA

  公开号：WO2015052283A1

  公开（公告）日：2015-04-16

  The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof : It further discloses a pharmaceutical composition comprising the compounds of Formula (I) and their uses as anti-proliferative and pro-apoptotic agents for cancer therapy.

  本发明涉及式（I）的化合物或其药用可接受的盐或溶剂：还揭示了一种包括式（I）化合物的药物组合物，以及它们作为抗增殖和促凋亡剂用于癌症治疗的用途。
• Metal Complexes with Nitronyl Nitroxide Substituted Phenolate Ligands Providing New Magnetic Exchange Interaction Pathways − Synthesis, Structures, Magnetic Dilution Studies, and Ab Initio Calculations
  作者：Ulrich Schatzschneider、Thomas Weyhermüller、Eva Rentschler

  DOI：10.1002/1099-0682(200109)2001:10<2569::aid-ejic2569>3.0.co;2-3

  日期：2001.9

  The synthesis and magnetic properties of seven new nitronyl nitroxide substituted phenolates with chelating amine groups are reported. Copper(II) and nickel(II) complexes prepared with these ligands are structurally and magnetically characterized, showing exchange interactions between the metal and the radical ligands through the phenolate oxygen. Magnetically diluted samples are prepared by embedding

  报道了七种新的具有螯合胺基团的硝酰基硝基氧取代酚盐的合成和磁性。用这些配体制备的铜 (II) 和镍 (II) 配合物在结构和磁性上都进行了表征，显示出金属和自由基配体之间通过酚氧的交换相互作用。通过将化合物嵌入聚（氯乙烯）薄膜中以抑制分子间交换相互作用来制备磁性稀释样品。该方法首次以定量方式用于分离自由基-金属系统中的分子内和分子间交换相互作用。DFT 计算进一步证实了实验确定的基态。
• DIARYLALKYLAMINE REV-ERB ANTAGONISTS AND THEIR USE AS MEDICAMENTS
  申请人：FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA

  公开号：US20160237057A1

  公开（公告）日：2016-08-18

  The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof: It further discloses a pharmaceutical composition comprising the compounds of Formula (I) and their uses as anti-proliferative and pro-apoptotic agents for cancer therapy.

  本发明涉及式（I）的化合物或其药学上可接受的盐或溶剂：它进一步揭示了包含式（I）化合物的制药组合物以及它们作为抗增殖和促凋亡剂用于癌症治疗的用途。
• 3-Hydroxy-<i>N</i>′-arylidenepropanehydrazonamides with Halo-Substituted Phenanthrene Scaffolds Cure <i>P. berghei</i> Infected Mice When Administered Perorally
  作者：Michael Leven、Tanja C. Knaab、Jana Held、Sandra Duffy、Stephan Meister、Christoph Fischli、Diane Meitzner、Ursula Lehmann、Beate Lungerich、Krystina Kuna、Petra Stahlke、Michael J. Delves、Mirko Buchholz、Elizabeth A. Winzeler、Vicky M. Avery、Benjamin Mordmüller、Sergio Wittlin、Thomas Kurz

  DOI：10.1021/acs.jmedchem.7b00140

  日期：2017.7.27

  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.
• US9611245B2
  申请人：——

  公开号：US9611245B2

  公开（公告）日：2017-04-04