2',3-dichlorobiphenyl-4-amine | 1148126-06-0

• 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',3-dichlorobiphenyl-4-amine
• 英文别名: 2-Chloro-4-(2-chlorophenyl)aniline
• CAS: 1148126-06-0
• 化学式: C₁₂H₉Cl₂N
• 分子量: 238.116
• InChiKey: KZOFAYZZCKBNMV-UHFFFAOYSA-N

物化性质

• 熔点：
  45-47 °C
• 沸点：
  337.3±27.0 °C(predicted)
• 密度：
  1.316±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 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

反应信息

• 作为反应物：
  描述：

  5-甲基-4-异恶唑羰酰氯 、 2',3-dichlorobiphenyl-4-amine 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 以0.21 g的产率得到N-(2',3-dichlorobiphenyl-4-yl)-5-methylisoxazole-4-carboxamide
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Characterization of Inhibitors of Human and Plasmodium falciparum Dihydroorotate Dehydrogenases

  摘要：

  Pyrimidine biosynthesis is an attractive drug target in a variety of organisms, including humans and the malaria parasite Plasmodium falciparum. Dihydroorotate dehydrogenase, an enzyme catalyzing the only redox reaction of the pyrimidine biosynthesis pathway, is a well-characterized target for chemotherapeutical intervention. In this study, we have applied SPROUT-LeadOpt, a software package for structure-based drug discovery and lead optimization, to improve the binding of the active metabolite of the anti-inflammatory drug leflunomide to the target cavities of the P. falciparum and human dihydroorotate dehydrogenases. Following synthesis of a library of compounds based upon the SPROUT-optimized molecular scaffolds, a series of inhibitors generally showing good inhibitory activity was obtained, in keeping with the SPROUT-LeadOpt predictions. Furthermore, cocrystal structures of five of these SPROUT-designed inhibitors bound in the ubiquinone binding cavity of the human dihydroorotate dehydrogenase are also analyzed.

  DOI：

  10.1021/jm800963t
• 作为产物：
  描述：

  2-氯苯基硼酸 、 4-溴-2-氯苯胺 在 palladium diacetate 、 potassium carbonate 、 三苯基膦 作用下， 以 甲苯 为溶剂， 反应 24.0h， 以62%的产率得到2',3-dichlorobiphenyl-4-amine
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Characterization of Inhibitors of Human and Plasmodium falciparum Dihydroorotate Dehydrogenases

  摘要：

  Pyrimidine biosynthesis is an attractive drug target in a variety of organisms, including humans and the malaria parasite Plasmodium falciparum. Dihydroorotate dehydrogenase, an enzyme catalyzing the only redox reaction of the pyrimidine biosynthesis pathway, is a well-characterized target for chemotherapeutical intervention. In this study, we have applied SPROUT-LeadOpt, a software package for structure-based drug discovery and lead optimization, to improve the binding of the active metabolite of the anti-inflammatory drug leflunomide to the target cavities of the P. falciparum and human dihydroorotate dehydrogenases. Following synthesis of a library of compounds based upon the SPROUT-optimized molecular scaffolds, a series of inhibitors generally showing good inhibitory activity was obtained, in keeping with the SPROUT-LeadOpt predictions. Furthermore, cocrystal structures of five of these SPROUT-designed inhibitors bound in the ubiquinone binding cavity of the human dihydroorotate dehydrogenase are also analyzed.

  DOI：

  10.1021/jm800963t

文献信息

• [EN] NOVEL SMALL MOLECULE INHIBITORS OF TEAD TRANSCRIPTION FACTORS<br/>[FR] NOUVEAUX INHIBITEURS À PETITES MOLÉCULES DE FACTEURS DE TRANSCRIPTION TEAD
  申请人：MASSACHUSETTS GEN HOSPITAL

  公开号：WO2020190774A1

  公开（公告）日：2020-09-24

  The present disclosure compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the TEAD transcription factor, and are useful in the treatment of diseases related to the activity of TEAD transcription factor including, e.g., cancer and other diseases.

  本公开涉及化合物及其组合物和使用方法。这些化合物抑制TEAD转录因子的活性，并可用于治疗与TEAD转录因子活性相关的疾病，例如癌症和其他疾病。
• Structure-Based Design, Synthesis, and Characterization of Inhibitors of Human and <i>Plasmodium falciparum</i> Dihydroorotate Dehydrogenases
  作者：Matthew Davies、Timo Heikkilä、Glenn A. McConkey、Colin W. G. Fishwick、Mark R. Parsons、A. Peter Johnson

  DOI：10.1021/jm800963t

  日期：2009.5.14

  Pyrimidine biosynthesis is an attractive drug target in a variety of organisms, including humans and the malaria parasite Plasmodium falciparum. Dihydroorotate dehydrogenase, an enzyme catalyzing the only redox reaction of the pyrimidine biosynthesis pathway, is a well-characterized target for chemotherapeutical intervention. In this study, we have applied SPROUT-LeadOpt, a software package for structure-based drug discovery and lead optimization, to improve the binding of the active metabolite of the anti-inflammatory drug leflunomide to the target cavities of the P. falciparum and human dihydroorotate dehydrogenases. Following synthesis of a library of compounds based upon the SPROUT-optimized molecular scaffolds, a series of inhibitors generally showing good inhibitory activity was obtained, in keeping with the SPROUT-LeadOpt predictions. Furthermore, cocrystal structures of five of these SPROUT-designed inhibitors bound in the ubiquinone binding cavity of the human dihydroorotate dehydrogenase are also analyzed.