2,4-bis(benzyloxy)-5-isopropylaniline | 1383717-80-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,4-bis(benzyloxy)-5-isopropylaniline
• 英文别名: 1,5-Bis-benzyloxy-2-isopropyl-4-amino-benzene；2,4-bis(phenylmethoxy)-5-propan-2-ylaniline
• CAS: 1383717-80-3
• 化学式: C₂₃H₂₅NO₂
• 分子量: 347.457
• InChiKey: PABSDEBPYZCAJX-UHFFFAOYSA-N

物化性质

• 沸点：
  524.5±50.0 °C(Predicted)
• 密度：
  1.116±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  44.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,4-bis(benzyloxy)-5-isopropylaniline 在 chloro(pentamethylcyclopentadienyl)ruthenium(II) tetramer 亚硝酸特丁酯 、 叠氮基三甲基硅烷 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 27.5h， 生成 1-(2,4-bis-benzyloxy-5-isopropyl-phenyl)-5-(4-methanesulfonyloxy-methyl-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid methyl ester
  参考文献：
  名称：

  [EN] ARYL TRIAZOLE COMPOUNDS WITH ANTITUMOURAL ACTIVITY
  [FR] COMPOSÉS ARYL TRIAZOLE AYANT UNE ACTIVITÉ ANTI-TUMORALE

  摘要：

  本发明涉及具有抗肿瘤活性的Formula I的芳基三唑衍生物，作为一个可能的生物靶标，通过分子伴侣热休克蛋白90（Hsp90）的抑制作用。该发明包括在医学上使用这些化合物，涉及癌症疾病以及其他需要抑制Hsp90的疾病，以及含有这些化合物的药物组合物。

  公开号：

  WO2012084602A1
• 作为产物：
  描述：

  2-(2,4-bis(benzyloxy)phenyl)propan-2-ol 在 三乙基硅烷 、 硝酸 、 铁粉 、 氯化铵 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 5.67h， 生成 2,4-bis(benzyloxy)-5-isopropylaniline
  参考文献：
  名称：

  [EN] HEAT SHOCK PROTEIN 90 INHIBITORS
  [FR] INHIBITEURS DE LA PROTÉINE DE CHOC THERMIQUE 90

  摘要：

  以下是公式（I）中所示的取代芳香化合物：（公式I）。公式（I）中每个变量的定义出现在规范中。还披露了含有其中一种取代芳香化合物的药物组合物。进一步披露了使用这些化合物中的一种来治疗与HSP90相关的医疗状况的方法。

  公开号：

  WO2018171575A1

文献信息

• Design and Synthesis of Hsp90 Inhibitors with B‐Raf and PDHK1 Multi‐Target Activity
  作者：Luca Pinzi、Francesca Foschi、Michael S. Christodoulou、Daniele Passarella、Giulio Rastelli

  DOI：10.1002/open.202100131

  日期：2021.12

  ad hoc ligands has been designed by integrating molecular fragments of known inhibitors of anticancer drug targets. The compounds were docked into the respective targets, and six derivatives were synthesized to be in vitro tested. Molecular dynamics studies were finally performed to provide further insights into the structural basis of the experimentally observed activities.

  多任务配体：通过整合已知抗癌药物靶标抑制剂的分子片段，设计了一组特设配体。将这些化合物对接到各自的靶标上，合成了六种衍生物进行体外测试。最终进行了分子动力学研究，以进一步了解实验观察到的活动的结构基础。
• ARYL TRIAZOLE COMPOUNDS WITH ANTITUMOURAL ACTIVITY
  申请人：Giannini Giuseppe

  公开号：US20140329812A1

  公开（公告）日：2014-11-06

  The present invention relates to aryl triazole derivatives of Formula I having antitumoural activity through, as one possible biological target, the molecular chaperone heat shock protein 90 (Hsp90) inhibition. The invention includes the use of such compounds in medicine, in relation to cancer disease as well as other diseases where an inhibition of Hsp90 is responsive, and the pharmaceutical composition containing such compounds.

  本发明涉及公式I的芳基三唑衍生物，通过作为可能的生物靶点之一，分子伴侣热休克蛋白90（Hsp90）抑制具有抗肿瘤活性。本发明包括将这些化合物用于医学，与癌症疾病以及其他需要抑制Hsp90的疾病有关，并且包含这些化合物的制药组合物。
• Aryl triazole compounds with antitumoural activity
  申请人：Giannini Giuseppe

  公开号：US09302998B2

  公开（公告）日：2016-04-05

  The present invention relates to aryl triazole derivatives of Formula I having antitumoural activity through, as one possible biological target, the molecular chaperone heat shock protein 90 (Hsp90) inhibition. The invention includes the use of such compounds in medicine, in relation to cancer disease as well as other diseases where an inhibition of Hsp90 is responsive, and the pharmaceutical composition containing such compounds.

  本发明涉及具有抗肿瘤活性的公式I的芳基三唑衍生物，其通过分子伴侣热休克蛋白90（Hsp90）抑制作为一种可能的生物靶标。本发明包括在医学上使用这些化合物，涉及癌症以及其他需要抑制Hsp90的疾病，以及含有这些化合物的制药组合物。
• Synthesis and Evaluation of New Hsp90 Inhibitors Based on a 1,4,5-Trisubstituted 1,2,3-Triazole Scaffold
  作者：Maurizio Taddei、Serena Ferrini、Luca Giannotti、Massimo Corsi、Fabrizio Manetti、Giuseppe Giannini、Loredana Vesci、Ferdinando M. Milazzo、Domenico Alloatti、Mario B. Guglielmi、Massimo Castorina、Maria L. Cervoni、Marcella Barbarino、Rosanna Foderà、Valeria Carollo、Claudio Pisano、Silvia Armaroli、Walter Cabri

  DOI：10.1021/jm401536b

  日期：2014.3.27

  Ruthenium catalyzed 1,3-cycloaddition (click chemistry) of an azido moiety installed on dihydroxycumene scaffold with differently substituted aryl propiolates gave a new family of 1,4,5-trisubstituted triazole carboxylic acid derivatives that showed high affinity toward Hsp90 associated with cell proliferation inhibition, both in nanomolar range. The 1,5 arrangement of the resorcinol, the aryl moieties, and the presence of an alkyl (secondary) amide in position 4 of the triazole ring were essential to get high activity. Docking simulations suggested that the triazoles penetrate the Hsp90 ATP binding site. Some 1,4,5-trisubstituted triazole carboxamides induced dramatic depletion of the examined client proteins and a very strong increase in the expression levels of the chaperone Hsp70. In vitro metabolic stability and in vivo preliminary studies on selected compounds have shown promising results comparable to the potent Hsp90 inhibitor NVP-AUY922. One of them, (compound 18, SST0287CL1) was selected for further investigation as the most promising drug candidate.
• 4,5,6,7-Tetrahydro-isoxazolo-[4,5-c]-pyridines as a new class of cytotoxic Hsp90 inhibitors
  作者：Riccardo Baruchello、Daniele Simoni、Paolo Marchetti、Riccardo Rondanin、Stefania Mangiola、Cristiana Costantini、Maria Meli、Giuseppe Giannini、Loredana Vesci、Valeria Carollo、Tiziana Brunetti、Gianfranco Battistuzzi、Manlio Tolomeo、Walter Cabri

  DOI：10.1016/j.ejmech.2014.01.056

  日期：2014.4

  Hsp90 is considered an interesting therapeutic target for anticancer drug development. Here we describe a new class of 4,5,6,7-tetrahydro-isoxazolo-[4,5-c]pyridine compounds. A small library of derivatives has been synthesized and investigated. Some reported compounds show interesting properties combining both notable binding to Hsp90 and potent cell growth inhibitory activity. N-5 substitution with a 2,4 resorcinol carboxamide appears crucial for activity. Moreover, a derivative bearing a hydroxamic acid residue bound to C-3 amide portion was found to inhibit both Hsp90 and HDAC6. (C) 2014 Elsevier Masson SAS. All rights reserved.