2-(cyclohexylamino)-N-(2,5-dihydroxyphenyl)acetamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(cyclohexylamino)-N-(2,5-dihydroxyphenyl)acetamide
• 化学式: C₁₄H₂₀N₂O₃
• 分子量: 264.324
• InChiKey: IFGKCXKKPDHRHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  81.6
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(cyclohexylamino)-N-(2,5-dihydroxyphenyl)acetamide 在 双氧水 、 氧气 作用下， 以 aq. phosphate buffer 为溶剂， 生成 、
  参考文献：
  名称：

  Design of a hydrogen peroxide-activatable agent that specifically targets cancer cells

  摘要：

  Some cancers, like acute myeloid leukemia (AML), use reactive oxygen species to endogenously activate cell proliferation and angiogenic signaling cascades. Thus many cancers display increases in reactive oxygen like hydrogen peroxide concentrations. To translate this finding into a therapeutic strategy we designed new hydrogen peroxide-activated agents with two key molecular pharmacophores. The first pharmacophore is a peroxide-acceptor and the second is a pendant amine. The acceptor is an N-(2,5-dihydroxyphenyl) acetamide susceptible to hydrogen peroxide oxidation. We hypothesized that selectivity between AML and normal cells could be achieved by tuning the pendant amine. Synthesis and testing of fourteen compounds that differed at the pendent amine led to the identification of an agent (14) with 2 mu M activity against AML cancer cells and an eleven fold-lower activity in healthy CD34+ blood stem cells. Interestingly, analysis shows that upon oxidation the pendant amine cyclizes, ejecting water, with the acceptor to give a bicyclic compound capable of reacting with nucleophiles. Preliminary mechanistic investigations show that AML cells made from addition of two oncogenes (NrasG12D and MLL-AF9) increase the ROS-status, is initially an anti-oxidant as hydrogen peroxide is consumed to activate the pro-drug, and cells respond by upregulating electrophilic defense as visualized by Western blotting of KEAP1. Thus, using this chemical approach we have obtained a simple, potent, and selective ROS-activated anti-AML agent. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.10.029
• 作为产物：
  描述：

  2-氯-N-(2,5-二甲氧基苯基)乙酰胺 在 三溴化硼 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 14.0h， 生成 2-(cyclohexylamino)-N-(2,5-dihydroxyphenyl)acetamide
  参考文献：
  名称：

  [EN] HYDROGEN PEROXIDE-ACTIVATED COMPOUNDS AS SELECTIVE ANTI-CANCER THERAPEUTICS
  [FR] COMPOSÉS ACTIVÉS PAR DU PEROXYDE D'HYDROGÈNE SERVANT D'AGENTS THÉRAPEUTIQUES ANTI-CANCÉREUX SÉLECTIFS

  摘要：

  提供的是以下式I的化合物：式I的化合物在过氧化氢的存在下被激活，因此是针对与升高活性氧种（ROS）相关的癌症的选择性抗癌治疗剂。还提供了用于治疗与ROS增加相关的癌症的方法和药物组合物。

  公开号：

  WO2016054486A1

文献信息

• Self‐Cyclizing Antioxidants to Prevent DNA Damage Caused by Hydroxyl Radical
  作者：Safnas F. AbdulSalam、Purujit N. Gurjar、Haizhou Zhu、Jing Liu、Emma S. Johnson、Ana Luisa Kadekaro、Julio Landero‐Figueroa、Edward J. Merino

  DOI：10.1002/cbic.201700341

  日期：2017.10.18

  Stable and selective antioxidants: We report a new class of self-cyclizing antioxidants to prevent hydroxyl-radical-mediated DNA damage. The lead agent lowers the levels of reactive oxygen in cells, and prevents the formation of oxazolone lesions (dZ) in cellular DNA upon exposure to oxidative-stress-inducing arsenic trioxide.

  稳定和选择性的抗氧化剂：我们报告了一种新型的自环抗氧化剂，可防止羟基自由基介导的DNA损伤。铅剂可降低细胞中活性氧的水平，并防止暴露于氧化应激诱导的三氧化二砷时细胞DNA中恶唑酮损伤（dZ）的形成。
• Hydrogen peroxide-activated compounds as selective anti-cancer therapeutics
  申请人：University of Cincinnati

  公开号：US10071954B2

  公开（公告）日：2018-09-11

  Provided are compounds according to the following Formula I: The Formula I compounds are activated in the presence of hydrogen peroxide and are therefore selective anti-cancer therapeutics for cancers associated with elevated reactive oxygen species (ROS). Also provided are methods and pharmaceutical compositions for treating cancers associated with increased ROS.

  本发明提供了符合下式 I 的化合物： 式 I 化合物在过氧化氢存在下被激活，因此是针对与活性氧（ROS）升高相关的癌症的选择性抗癌疗法。此外，还提供了治疗与 ROS 增高相关的癌症的方法和药物组合物。
• HYDROGEN PEROXIDE-ACTIVATED COMPOUNDS AS SELECTIVE ANTI-CANCER THERAPEUTICS
  申请人：University of Cincinnati

  公开号：EP3200780B1

  公开（公告）日：2020-02-19
• EP3200780A1
  申请人：——

  公开号：EP3200780A1

  公开（公告）日：2017-08-09
• Hydrogen Peroxide-Activated Compounds as Selective Anti-Cancer Therapeutics
  申请人：UNIVERSITY OF CINCINNATI

  公开号：US20160318849A1

  公开（公告）日：2016-11-03

  Provided are compounds according to the following Formula I: The Formula I compounds are activated in the presence of hydrogen peroxide and are therefore selective anti-cancer therapeutics for cancers associated with elevated reactive oxygen species (ROS). Also provided are methods and pharmaceutical compositions for treating cancers associated with increased ROS.