3',4'-difluoro-[1,1'-biphenyl]-3-amine | 866108-75-0

• 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: 3',4'-difluoro-[1,1'-biphenyl]-3-amine
• 英文别名: 3-(3,4-Difluorophenyl)aniline
• CAS: 866108-75-0
• 化学式: C₁₂H₉F₂N
• 分子量: 205.207
• InChiKey: PGBITXQZBBLNRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 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：
  3

反应信息

• 作为反应物：
  描述：

  3',4'-difluoro-[1,1'-biphenyl]-3-amine 在 三甲基溴硅烷 作用下， 以 乙腈 为溶剂， 反应 20.0h， 生成 [[3-(3,4-Difluorophenyl)anilino]-phosphono-methyl]phosphonic acid
  参考文献：
  名称：

  Bisphosphonate Inhibition of the Exopolyphosphatase Activity of the Trypanosoma brucei Soluble Vacuolar Pyrophosphatase

  摘要：

  Trypanosoma brucei, the causative agent of African trypanosomiasis, contains a soluble, vacuolar pyrophosphatase, TbVSP1, not present in humans, which is essential for the growth of bloodstream forms in their mammalian host. Here, we report the inhibition of a recombinant TbVSP1 expressed in Escherichia coli by a panel of 81 bisphosphonates. The IC50 values were found to vary from similar to 2 to 850 mu M. We then used 3D QSAR (comparative molecular field and comparative molecular similarity index; CoMFA and CoMSIA) methods to analyze the enzyme inhibition results. The R-2 values for the experimental versus the QSAR-predicted activities were 0.78 or 0.61 for CoMFA and 0.79 or 0.68 for CoMSIA, for two different alignments. The root-mean-square (rms) pIC(50) error for the best CoMFA model was 0.41 for five test sets of five activity predictions, which translates to a factor of similar to 2.6 error in IC50 prediction. For CoMSIA, the rms pIC(50) error and error factors were 0.35 and 2.2, respectively. In general, the most active compounds contained both a single aromatic ring and a hydrogen bond donor feature. Thirteen of the more potent compounds were then tested in vivo in a mouse model of T. brucei infection. The most active compound in vivo provided a 40% protection from death with no apparent side effects, suggesting that further development of such compounds may be of interest.

  DOI：

  10.1021/jm058220g
• 作为产物：
  描述：

  3-溴-N-乙酰苯胺 在 盐酸 、 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 甲苯 为溶剂， 反应 10.0h， 生成 3',4'-difluoro-[1,1'-biphenyl]-3-amine
  参考文献：
  名称：

  Bisphosphonate Inhibition of the Exopolyphosphatase Activity of the Trypanosoma brucei Soluble Vacuolar Pyrophosphatase

  摘要：

  Trypanosoma brucei, the causative agent of African trypanosomiasis, contains a soluble, vacuolar pyrophosphatase, TbVSP1, not present in humans, which is essential for the growth of bloodstream forms in their mammalian host. Here, we report the inhibition of a recombinant TbVSP1 expressed in Escherichia coli by a panel of 81 bisphosphonates. The IC50 values were found to vary from similar to 2 to 850 mu M. We then used 3D QSAR (comparative molecular field and comparative molecular similarity index; CoMFA and CoMSIA) methods to analyze the enzyme inhibition results. The R-2 values for the experimental versus the QSAR-predicted activities were 0.78 or 0.61 for CoMFA and 0.79 or 0.68 for CoMSIA, for two different alignments. The root-mean-square (rms) pIC(50) error for the best CoMFA model was 0.41 for five test sets of five activity predictions, which translates to a factor of similar to 2.6 error in IC50 prediction. For CoMSIA, the rms pIC(50) error and error factors were 0.35 and 2.2, respectively. In general, the most active compounds contained both a single aromatic ring and a hydrogen bond donor feature. Thirteen of the more potent compounds were then tested in vivo in a mouse model of T. brucei infection. The most active compound in vivo provided a 40% protection from death with no apparent side effects, suggesting that further development of such compounds may be of interest.

  DOI：

  10.1021/jm058220g

文献信息

• [EN] SUBSTITUTED N-([1,1'-BIPHENYL]-3-YL)-[1,1'-BIPHENYL]-3-CARBOXAMIDE ANALOGS AS INHIBITORS FOR BETA-CATENIN/B-CELL LYMPHOMA 9 INTERACTIONS<br/>[FR] ANALOGUES DE N-([1,1'-BIPHÉNYL]-3-YL)-[1,1'-BIPHÉNYL]-3-CARBOXAMIDE SUBSTITUÉ UTILISÉS EN TANT QU'INHIBITEURS DES INTERACTIONS BÊTA-CATÉNINE/LYMPHOME À CELLULES B 9
  申请人：UNIV UTAH RES FOUND

  公开号：WO2016168524A1

  公开（公告）日：2016-10-20

  In one aspect, the invention relates to substituted N-([1,1'-biphenyl]-3-yl)-[1,1'- biphenyl]-3-carboxamide analogues, derivatives thereof, and related compound; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders, e.g., various tumors and cancers, associated with β-Catenin/BCL9 protein-protein interaction dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，该发明涉及替代N-([1,1'-联苯基]-3-基)-[1,1'-联苯基]-3-羧酰胺类似物，其衍生物以及相关化合物；制备这些化合物的合成方法；包括这些化合物的药物组合物；以及使用这些化合物和组合物治疗与β-Catenin/BCL9蛋白质相互作用功能障碍相关的疾病，例如各种肿瘤和癌症的方法。本摘要旨在作为在特定领域进行搜索的扫描工具，并不打算限制本发明。
• [EN] HETEROCYCLIC DERIVATIVES AND USE THEREOF<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES ET LEUR UTILISATION
  申请人：C & C RES LAB

  公开号：WO2014196793A1

  公开（公告）日：2014-12-11

  A heterocyclic derivative represented by formula (I), or a pharmaceutically acceptable salt or a stereoisomer thereof, which has an inhibitory effect on the activation of STAT3 protein, and is useful for the prevention or treatment of diseases associated with the activation of STAT3 protein.

  由式(I)表示的杂环衍生物，或其药用可接受的盐或立体异构体，对STAT3蛋白激活具有抑制作用，并可用于预防或治疗与STAT3蛋白激活相关的疾病。
• [EN] PYRAZOLO[4,3-D]PYRIMIDINES AS KINASE INHIBITORS<br/>[FR] PYRAZOLO[4,3-D]PYRIMIDINES UTILES EN TANT QU'INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2014060112A1

  公开（公告）日：2014-04-24

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及具有式（I）的新化合物，其能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复的激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体。这些化合物可用于治疗多种疾病。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和激素相关疾病。
• Novel kinase inhibitors
  申请人：Thormann Michael

  公开号：US20120329785A1

  公开（公告）日：2012-12-27

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases.

  本发明涉及式（I）的新型化合物，这些化合物能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复的激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体。这些化合物可用于治疗各种疾病。
• NOVEL KINASE INHIBITORS
  申请人：ORIGENIS GMBH

  公开号：US20150259340A1

  公开（公告）日：2015-09-17

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及式（I）的新型化合物，能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复的激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体。这些化合物可用于治疗各种疾病。这些疾病包括自身免疫性疾病、炎症性疾病、骨病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和与激素相关的疾病。