3,4-二氯苯基乙酰苯胺 | 27816-82-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3,4-二氯苯基乙酰苯胺
• 英文名称: N-(3,4-dichloro-phenyl)-2-phenyl-acetamide
• 英文别名: 3',4'-Dichlorophenylacetanilide；N-(3,4-dichlorophenyl)-2-phenylacetamide
• CAS: 27816-82-6
• 化学式: C₁₄H₁₁Cl₂NO
• mdl: MFCD00043753
• 分子量: 280.153
• InChiKey: WOLDJAKASQLODM-UHFFFAOYSA-N

物化性质

• 熔点：
  132 °C
• 沸点：
  469.6±45.0 °C(Predicted)
• 密度：
  1.352±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  3,4-二氯苯基乙酰苯胺 在 草酰氯 、 potassium tert-butylate 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.34h， 生成 1-(3,4-dichloro-phenyl)-3-morpholin-4-yl-4-phenyl-pyrrole-2,5-dione
  参考文献：
  名称：

  An Optimized RAD51 Inhibitor That Disrupts Homologous Recombination without Requiring Michael Acceptor Reactivity

  摘要：

  Homologous recombination (HR) is an essential process in cells that provides repair of DNA double-strand breaks and lesions that block DNA replication. RAD51 is an evolutionarily conserved protein that is central to HR. Overexpression of RAD51 protein is common in cancer cells and represents a potential therapeutic target in oncology. We previously described a chemical inhibitor of RAD51, called RI-1 (referred to as compound 1 in this report). The chloromaleimide group of this compound is thought to act as a Michael acceptor and react with the thiol group on C319 of RAD51, using a conjugate addition-elimination mechanism. In order to reduce the likelihood of off-target effects and to improve compound stability in biological systems, we developed an analogue of compound 1 that lacks maleimide-based reactivity but retains RAD51 inhibitory activity. This compound, 1-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)-4-morpholino-1H-pyrrole-2,5-dione, named RI-2 (referred to as compound 7a in this report), appears to bind reversibly to the same site on the RAD51 protein as does compound 1. Like compound 1, compound 7a specifically inhibits HR repair in human cells.

  DOI：

  10.1021/jm301565b
• 作为产物：
  描述：

  苯乙酸 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.25h， 生成 3,4-二氯苯基乙酰苯胺
  参考文献：
  名称：

  An Optimized RAD51 Inhibitor That Disrupts Homologous Recombination without Requiring Michael Acceptor Reactivity

  摘要：

  Homologous recombination (HR) is an essential process in cells that provides repair of DNA double-strand breaks and lesions that block DNA replication. RAD51 is an evolutionarily conserved protein that is central to HR. Overexpression of RAD51 protein is common in cancer cells and represents a potential therapeutic target in oncology. We previously described a chemical inhibitor of RAD51, called RI-1 (referred to as compound 1 in this report). The chloromaleimide group of this compound is thought to act as a Michael acceptor and react with the thiol group on C319 of RAD51, using a conjugate addition-elimination mechanism. In order to reduce the likelihood of off-target effects and to improve compound stability in biological systems, we developed an analogue of compound 1 that lacks maleimide-based reactivity but retains RAD51 inhibitory activity. This compound, 1-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)-4-morpholino-1H-pyrrole-2,5-dione, named RI-2 (referred to as compound 7a in this report), appears to bind reversibly to the same site on the RAD51 protein as does compound 1. Like compound 1, compound 7a specifically inhibits HR repair in human cells.

  DOI：

  10.1021/jm301565b

文献信息

• [EN] METHODS AND COMPOSITIONS INVOLVING RAD51 INHIBITORS<br/>[FR] PROCÉDÉS ET COMPOSITIONS IMPLIQUANT DES INHIBITEURS DE RAD51
  申请人：UNIV CHICAGO

  公开号：WO2014085545A1

  公开（公告）日：2014-06-05

  The present invention concerns methods and compositions involving inhibitors and of RAD51, a protein involved in homologous recombination. In some embodiments, there are methods for sensitizing cells to the effects of DNA damaging agents, which can have particular applications for cancer patients. In some embodiments of the invention, the RAD51 inhibitor is a small molecule that directly affects RAD51 activity, such as its ability to promote filament formation.

  本发明涉及涉及RAD51抑制剂和RAD51的方法和组合物，RAD51是参与同源重组的蛋白质。在某些实施例中，有一些方法可以使细胞对DNA损伤剂的影响变得更敏感，这对癌症患者可能具有特殊应用。在本发明的某些实施例中，RAD51抑制剂是一种直接影响RAD51活性的小分子，例如其促进丝状物形成的能力。
• METHODS AND COMPOSITIONS INVOLVING RAD51 INHIBITORS
  申请人：The University of Chicago

  公开号：US20150306069A1

  公开（公告）日：2015-10-29

  The present invention concerns methods and compositions involving inhibitors and of RAD51, a protein involved in homologous recombination. In some embodiments, there are methods for sensitizing cells to the effects of DNA damaging agents, which can have particular applications for cancer patients. In some embodiments of the invention, the RAD51 inhibitor is a small molecule that directly affects RAD51 activity, such as its ability to promote filament formation.

  本发明涉及抑制剂和RAD51的组合物的方法，RAD51是参与同源重组的蛋白质。在某些实施例中，有方法使细胞对DNA损伤剂的影响更为敏感，这可以特别应用于癌症患者。在本发明的某些实施例中，RAD51抑制剂是一种直接影响RAD51活性的小分子，例如其促进丝状物形成的能力。
• Methods and compositions involving RAD51 inhibitors
  申请人：The University of Chicago

  公开号：US10912761B2

  公开（公告）日：2021-02-09

  The present invention concerns methods and compositions involving inhibitors and of RAD51, a protein involved in homologous recombination. In some embodiments, there are methods for sensitizing cells to the effects of DNA damaging agents, which can have particular applications for cancer patients. In some embodiments of the invention, the RAD51 inhibitor is a small molecule that directly affects RAD51 activity, such as its ability to promote filament formation.

  本发明涉及 RAD51（一种参与同源重组的蛋白质）的抑制剂和组合物。在某些实施方案中，有使细胞对 DNA 损伤剂的作用敏感的方法，这对癌症患者有特殊的应用价值。在本发明的某些实施方案中，RAD51 抑制剂是一种直接影响 RAD51 活性的小分子，如其促进细丝形成的能力。
• An Optimized RAD51 Inhibitor That Disrupts Homologous Recombination without Requiring Michael Acceptor Reactivity
  作者：Brian Budke、Jay H. Kalin、Michal Pawlowski、Anna S. Zelivianskaia、Megan Wu、Alan P. Kozikowski、Philip P. Connell

  DOI：10.1021/jm301565b

  日期：2013.1.10

  Homologous recombination (HR) is an essential process in cells that provides repair of DNA double-strand breaks and lesions that block DNA replication. RAD51 is an evolutionarily conserved protein that is central to HR. Overexpression of RAD51 protein is common in cancer cells and represents a potential therapeutic target in oncology. We previously described a chemical inhibitor of RAD51, called RI-1 (referred to as compound 1 in this report). The chloromaleimide group of this compound is thought to act as a Michael acceptor and react with the thiol group on C319 of RAD51, using a conjugate addition-elimination mechanism. In order to reduce the likelihood of off-target effects and to improve compound stability in biological systems, we developed an analogue of compound 1 that lacks maleimide-based reactivity but retains RAD51 inhibitory activity. This compound, 1-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)-4-morpholino-1H-pyrrole-2,5-dione, named RI-2 (referred to as compound 7a in this report), appears to bind reversibly to the same site on the RAD51 protein as does compound 1. Like compound 1, compound 7a specifically inhibits HR repair in human cells.

表征谱图