3′-fluorobiphenyl-3,4-diamine | 471240-30-9

• 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: 3′-fluorobiphenyl-3,4-diamine
• 英文别名: 5'-fluorobiphenyl-3,4-diamine；3'-fluoro-[1,1'-biphenyl]-3,4-diamine；3'-Fluoro-[1,1'-biphenyl]-3,4-diamine；4-(3-fluorophenyl)benzene-1,2-diamine
• CAS: 471240-30-9
• 化学式: C₁₂H₁₁FN₂
• 分子量: 202.231
• InChiKey: GOKJBZYEDJBACN-UHFFFAOYSA-N

物化性质

• 沸点：
  372.3±32.0 °C(Predicted)
• 密度：
  1.236±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 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：
  52
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3′-fluorobiphenyl-3,4-diamine 在 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成
  参考文献：
  名称：

  Identification of novel HDAC inhibitors through cell based screening and their evaluation as potential anticancer agents

  摘要：

  A series of benzimidazole based HDAC inhibitors have been rationally designed, synthesized and screened. The SAR of this new chemotype is described. The lead compound, 11e, showed strong activity in several cellular assays and demonstrated in vivo efficacy in mouse xenograft pancreatic cancer models. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.001
• 作为产物：
  描述：

  5-溴-2-硝基苯胺 在 四(三苯基膦)钯 、 palladium on activated charcoal 、 甲酸铵 、 potassium carbonate 作用下， 生成 3′-fluorobiphenyl-3,4-diamine
  参考文献：
  名称：

  Identification of novel HDAC inhibitors through cell based screening and their evaluation as potential anticancer agents

  摘要：

  A series of benzimidazole based HDAC inhibitors have been rationally designed, synthesized and screened. The SAR of this new chemotype is described. The lead compound, 11e, showed strong activity in several cellular assays and demonstrated in vivo efficacy in mouse xenograft pancreatic cancer models. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.001

文献信息

• [EN] PYRAZOLE DERIVATIVES AS MODULATORS OF THE WNT/B-CATENIN SIGNALING PATHWAY<br/>[FR] DÉRIVÉS DE PYRAZOLE UTILISÉS COMME MODULATEURS DE LA VOIE DE SIGNALISATION WNT/β-CATÉNINE
  申请人：SAMUMED LLC

  公开号：WO2020150545A1

  公开（公告）日：2020-07-23

  Pyrazole compounds (I) for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of a pyrazole compounds, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis Alzheimer's disease, lung disease, inflammation, auto-immune diseases and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as neurological conditions/disorders/diseases linked to overexpression of DYRK1A.

  本发明涉及用于治疗各种疾病和病理的吡唑化合物（I）。更具体地，本公开涉及使用吡唑化合物，在治疗通过激活Wnt途径信号特征的疾病（例如癌症、异常细胞增殖、血管生成、阿尔茨海默病、肺部疾病、炎症、自身免疫疾病和骨关节炎）中，调节由Wnt途径信号介导的细胞事件，以及与DYRK1A过度表达相关的神经症状/疾病。
• Discovery of New Benzothiazole-Based Inhibitors of Breakpoint Cluster Region-Abelson Kinase Including the T315I Mutant
  作者：Seunghee Hong、Jinhee Kim、Sun-Mi Yun、Hyunseung Lee、Yoonsu Park、Soon-Sun Hong、Sungwoo Hong

  DOI：10.1021/jm301891t

  日期：2013.5.9

  The existence of drug resistance caused by mutations in the break-point cluster region-Abelson tyrosine kinase (Bcr-Abl) kinase domain remains a clinical challenge due to limited effective treatment options for chronic myeloid leukemia (CML). Herein we report a novel series of benzothiazole-based inhibitors that are effective against wild-type and T315I mutant Bcr-Abl kinases. The original hit compound, nocodazole, was extensively modified through a structure-based drug design strategy, especially by varying the groups at the C2 and C6 positions of the scaffold. In addition, the introduction of water-solubilizing groups at the terminal ethyl group resulted in enhanced physicochemical properties and potency in cellular inhibition. Several compounds inhibited the kinase activity of both wild-type Bcr-Abl and the T315I mutant with IC50 values in the picomolar range and exhibited good antiproliferative effects on Ba/F3 cell lines transformed with either wild-type or T315I mutant Bcr-Abl.
• Discovery of Picomolar ABL Kinase Inhibitors Equipotent for Wild Type and T315I Mutant via Structure-Based de Novo Design
  作者：Hwangseo Park、Seunghee Hong、Jinhee Kim、Sungwoo Hong

  DOI：10.1021/ja311756u

  日期：2013.6.5

  Although the constitutively activated break-point cluster region-Abelson (ABL) tyrosine kinase is known to cause chronic myelogenous leukemia (CML), the prevalence of drug-resistant ABL mutants has made it difficult to develop effective anti-CML drugs. With the aim to identify new lead compounds for anti-CML drugs, we carried out a structure-based de novo design using the scoring function improved by implementing an accurate solvation free energy term. This approach led to the identification of ABL inhibitors equipotent for the wild type and the most drug-resistant T315I mutant of ABL at the picomolar level. Decomposition analysis of the binding free energy showed that a decrease in the desolvation cost for binding in the ATP-binding site could be as important as the strengthening of enzyme-inhibitor interaction to enhance the potency of an ABL inhibitor with structural modifications. A similar energetic feature was also observed in free energy perturbation (FEP) calculations. Consistent with the previous experimental and computational studies, the hydrogen bond interactions with the backbone groups of Met318 proved to be the most significant binding forces to stabilize the inhibitors in the ATP-binding sites of the wild type and T315I mutant. The results of molecular dynamics simulations indicated that the dynamic stabilities of the hydrogen bonds between the inhibitors and Met318 should also be considered in designing the potent common inhibitors of the wild-type and T315I mutant of ABL.
• Identification of novel HDAC inhibitors through cell based screening and their evaluation as potential anticancer agents
  作者：Tong Wang、Mario Sepulveda、Paul Gonzales、Stephen Gately

  DOI：10.1016/j.bmcl.2013.07.001

  日期：2013.9

  A series of benzimidazole based HDAC inhibitors have been rationally designed, synthesized and screened. The SAR of this new chemotype is described. The lead compound, 11e, showed strong activity in several cellular assays and demonstrated in vivo efficacy in mouse xenograft pancreatic cancer models. (C) 2013 Elsevier Ltd. All rights reserved.