4-氨基-3,5-二氯联苯 | 405058-01-7

• 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: 4-氨基-3,5-二氯联苯
• 英文名称: 3',5'-dichloro-[1,1'-biphenyl]-4-amine
• 英文别名: 4-amino-3′,5′-dichlorobiphenyl；3',5'-dichloro-biphenyl-4-ylamine；3'.5'-Dichlor-4-amino-diphenyl；3',5'-Dichlor-biphenyl-4-ylamin；4-Amino-3',5'-dichlorobiphenyl；4-(3,5-dichlorophenyl)aniline
• CAS: 405058-01-7
• 化学式: C₁₂H₉Cl₂N
• 分子量: 238.116
• InChiKey: IELLSGLWKOTCFM-UHFFFAOYSA-N

物化性质

• 沸点：
  370.6±27.0 °C(Predicted)
• 密度：
  1.316±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2921499090

反应信息

• 作为反应物：
  描述：

  4-氨基-3,5-二氯联苯 在 盐酸 作用下， 生成 3,4',5-三氯联苯
  参考文献：
  名称：

  Hinkel; Hey, Journal of the Chemical Society, 1928, p. 2787,2789

  摘要：

  DOI：
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 盐酸 、 tin(ll) chloride 作用下， 生成 4-氨基-3,5-二氯联苯
  参考文献：
  名称：

  Hinkel; Hey, Journal of the Chemical Society, 1928, p. 2787,2789

  摘要：

  DOI：

文献信息

• [EN] SMALL MOLECULE INDUCERS OF REACTIVE OXYGEN SPECIES AND INHIBITORS OF MITOCHONDRIAL ACTIVITY<br/>[FR] INDUCTEURS DE PETITES MOLÉCULES DE DÉRIVES RÉACTIFS DE L'OXYGÈNE ET INHIBITEURS DE L'ACTIVITÉ MITOCHONDRIALE
  申请人：UNIV MICHIGAN REGENTS

  公开号：WO2017155991A1

  公开（公告）日：2017-09-14

  This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a quinazolinedione structure which function as reactive oxygen species (ROS) inducers and inhibitors of mitochondrial activity within cancer cells (e.g., pancreatic cancer cells), and their use as therapeutics for the treatment of cancer (e.g., pancreatic cancer) and other diseases.

  这项发明属于药物化学领域。具体来说，该发明涉及一类具有喹唑啉二酮结构的小分子，其作为活性氧（ROS）诱导剂和对癌细胞（例如胰腺癌细胞）内线粒体活性的抑制剂，并将它们用作治疗癌症（例如胰腺癌）和其他疾病的药物。
• A Novel Redox Modulator Induces a GPX4-Mediated Cell Death That Is Dependent on Iron and Reactive Oxygen Species
  作者：Shuai Hu、Mario Sechi、Pankaj Kumar Singh、Lipeng Dai、Sean McCann、Duxin Sun、Mats Ljungman、Nouri Neamati

  DOI：10.1021/acs.jmedchem.0c01016

  日期：2020.9.10

  modulators have been developed as an attractive approach to treat cancer. Herein, we report the synthesis, identification, and biological evaluation of a quinazolinedione reactive oxygen species (ROS) inducer, QD394, with significant cytotoxicity in pancreatic cancer cells. QD394 shows a transcriptomic profile remarkably similar to napabucasin, a cancer stemness inhibitor. Both small molecules inhibit

  氧化还原调节剂已被开发为治疗癌症的有吸引力的方法。在此，我们报告了喹唑啉二酮活性氧 (ROS) 诱导剂 QD394 的合成、鉴定和生物学评估，该诱导剂在胰腺癌细胞中具有显着的细胞毒性。QD394 显示出与癌症干性抑制剂 napabucasin 非常相似的转录组学特征。这两种小分子都抑制 STAT3 磷酸化，增加细胞 ROS，并降低 GSH/GSSG 比率。此外，QD394 导致铁和 ROS 依赖性、GPX4 介导的细胞死亡，表明铁死亡是主要机制。重要的是，QD394 降低了 LRPPRC 和 PNPT1 的表达，这两种蛋白质参与线粒体 RNA 分解代谢过程，并且都与胰腺癌患者的总生存期呈负相关。药代动力学指导的先导优化产生了衍生物 QD394-Me，与 QD394 相比，它在小鼠中显示出改善的血浆稳定性和降低的毒性。总体而言，QD394 和 QD394-Me 代表了新型 ROS 诱导药物样化合物，值得进一步开发用于治疗胰腺癌。
• Small molecule inducers of reactive oxygen species and inhibitors of mitochondrial activity
  申请人：The Regents of the University of Michigan

  公开号：US10781183B2

  公开（公告）日：2020-09-22

  This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a quinazolinedione structure which function as reactive oxygen species (ROS) inducers and inhibitors of mitochondrial activity within cancer cells (e.g., pancreatic cancer cells), and their use as therapeutics for the treatment of cancer (e.g., pancreatic cancer) and other diseases.

  本发明属于药物化学领域。特别是，本发明涉及一类新的具有喹唑啉二酮结构的小分子，它们在癌细胞（如胰腺癌细胞）中可作为活性氧（ROS）诱导剂和线粒体活性抑制剂，并可用作治疗癌症（如胰腺癌）和其他疾病的疗法。
• Species-Selective Pyrimidineamine Inhibitors of <i>Trypanosoma brucei S</i>-Adenosylmethionine Decarboxylase
  作者：Oleg A. Volkov、Anthony J. Brockway、Stephen A. Wring、Michael Peel、Zhe Chen、Margaret A. Phillips、Jef K. De Brabander

  DOI：10.1021/acs.jmedchem.7b01654

  日期：2018.2.8

  New therapeutic options are needed for treatment of human African trypanosomiasis (HAT) caused by protozoan parasite Trypanosoma brucei. S-Adenosylmethionine decarboxylase (AdoMetDC) is an essential enzyme in the polyamine pathway of T. brucei. Previous attempts to target this enzyme were thwarted by the lack of brain penetration of the most advanced series. Herein, we describe a T. brucei AdoMetDC inhibitor series based on a pyrimidineamine pharmacophore that we identified by target-based high-throughput screening. The pyrimidineamines showed selectivity for T. brucei AdoMetDC over the human enzyme, inhibited parasite growth in whole-cell assay, and had good predicted blood-brain barrier penetration. The medicinal chemistry program elucidated structure-activity relationships within the series. Features of the series that were required for binding were revealed by determining the X-ray crystal structure of TbAdoMetDC bound to one analog. The pyrimidineamine series provides a novel starting point for an anti-HAT lead optimization.
• SMALL MOLECULE INDUCERS OF REACTIVE OXYGEN SPECIES AND INHIBITORS OF MITOCHONDRIAL ACTIVITY
  申请人：The Regents of The University of Michigan

  公开号：EP3426249A1

  公开（公告）日：2019-01-16