1-(4-fluoro-3-nitrophenyl)-N,N-dimethylmethanamine | 697305-64-9

• 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: 1-(4-fluoro-3-nitrophenyl)-N,N-dimethylmethanamine
• 英文别名: (4-fluoro-3-nitrobenzyl)dimethylamine
• CAS: 697305-64-9
• 化学式: C₉H₁₁FN₂O₂
• 分子量: 198.197
• InChiKey: NEWHVKQUJKNPII-UHFFFAOYSA-N

物化性质

• 沸点：
  273.6±25.0 °C(Predicted)
• 密度：
  1.222±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  49.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-fluoro-3-nitrophenyl)-N,N-dimethylmethanamine 在 盐酸 、 tin(II) chloride dihdyrate 、 溶剂黄146 作用下， 以 水 、 1,2-二氯乙烷 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  4-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazole and -pyrazole derivatives as potent and selective inhibitors of transforming growth factor-β type I receptor kinase

  摘要：

  A series of 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazoles and -pyrazoles 14a-c, 15a-c, 16a, 16b, 19a-d, 21a, and 21b has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. Among them, the pyrazole derivative 21b inhibited ALK5 phosphorylation with an IC50 value of 0.018 mu M and showed 95% inhibition at 0.03 mu M in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct. The 21b showed a high selectivity index of 284 against p38 alpha MAP kinase. The binding pose of 21b generated by docking analysis reveals that it fits well into the ATP binding cavity of ALK5 by forming several hydrogen bond interactions. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.03.022
• 作为产物：
  描述：

  4-氟-3-硝基苄醇 在 三溴化磷 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 2.42h， 生成 1-(4-fluoro-3-nitrophenyl)-N,N-dimethylmethanamine
  参考文献：
  名称：

  4-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazole and -pyrazole derivatives as potent and selective inhibitors of transforming growth factor-β type I receptor kinase

  摘要：

  A series of 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazoles and -pyrazoles 14a-c, 15a-c, 16a, 16b, 19a-d, 21a, and 21b has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. Among them, the pyrazole derivative 21b inhibited ALK5 phosphorylation with an IC50 value of 0.018 mu M and showed 95% inhibition at 0.03 mu M in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct. The 21b showed a high selectivity index of 284 against p38 alpha MAP kinase. The binding pose of 21b generated by docking analysis reveals that it fits well into the ATP binding cavity of ALK5 by forming several hydrogen bond interactions. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.03.022

文献信息

• [EN] AMINE COMPOUNDS<br/>[FR] DERIVES D'INDOLE SERVANT D'ANTAGONISTE DE SOMATOSTATINE
  申请人：TAKEDA CHEMICAL INDUSTRIES LTD

  公开号：WO2004046107A1

  公开（公告）日：2004-06-03

  The present invention provide a compound of the formula (I) wherein ring A represents an aromatic ring optionally having substituents; B, Y and Ya are the same or different and each represents a bond, etc.; R1 and R2 are the same or different and each represents a hydrogen atom, etc.; R3 represents a hydrogen atom, etc.; R4 and R5 are the same or different and each represents a hydrogen, etc.; R6 represents an indolyl group optionally having substituents; and Z and Za are the same or different and each represents a hydrogen atom, etc.; or a salt thereof or a prodrug thereof, having a somatostatin receptor binding inhibition activity and is useful for preventing and/or treating diseases associated with somatostatin.

  本发明提供了一种公式(I)的化合物，其中环A代表一个具有可选取代基的芳香环；B、Y和Ya相同或不同，分别代表一个键等；R1和R2相同或不同，每个代表一个氢原子等；R3代表一个氢原子等；R4和R5相同或不同，每个代表一个氢等；R6代表一个可选有取代基的吲哚基团；Z和Za相同或不同，每个代表一个氢原子等；或其盐或前药，具有生长抑素受体结合抑制活性，并且用于预防或治疗与生长抑素相关的疾病。
• Indole derivatives as somatostatin agonists or antagonists
  申请人：Abe Hidenori

  公开号：US20060223826A1

  公开（公告）日：2006-10-05

  The present invention provide a compound of the formula (I) wherein ring A represents an aromatic ring optionally having substituents; B, Y and Ya are the same or different and each represents a bond, etc.; R 1 and R 2 are the same or different and each represents a hydrogen atom, etc.; R 3 represents a hydrogen atom, etc.; R 4 and R 5 are the same or different and each represents a hydrogen, etc.; R 6 represents an indolyl group optionally having substituents; and Z and Za are the same or different and each represents a hydrogen atom, etc.; or a salt thereof or a prodrug thereof, having a somatostatin receptor binding inhibition activity and is useful for preventing and/or treating diseases associated with somatostatin.

  本发明提供了一种化合物(I)的公式，其中环A代表一种芳香环，可选地具有取代基; B、Y和Ya相同或不同，每个代表一种键等; R1和R2相同或不同，每个代表一个氢原子等; R3代表一个氢原子等; R4和R5相同或不同，每个代表一个氢等; R6代表一种吲哚基，可选地具有取代基; Z和Za相同或不同，每个代表一个氢原子等; 或其盐或前药，具有生长抑素受体结合抑制活性，并用于预防和/或治疗与生长抑素相关的疾病。
• Discovery of <i>N</i>-((4-([1,2,4]Triazolo[1,5-<i>a</i>]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1<i>H</i>-imidazol-2-yl)methyl)-2-fluoroaniline (EW-7197): A Highly Potent, Selective, and Orally Bioavailable Inhibitor of TGF-β Type I Receptor Kinase as Cancer Immunotherapeutic/Antifibrotic Agent
  作者：Cheng Hua Jin、Maddeboina Krishnaiah、Domalapally Sreenu、Vura B. Subrahmanyam、Kota S. Rao、Hwa Jeong Lee、So-Jung Park、Hyun-Ju Park、Kiho Lee、Yhun Yhong Sheen、Dae-Kee Kim

  DOI：10.1021/jm500115w

  日期：2014.5.22

  A series of 2-substituted-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyriclin-2-yl)imidazoles was synthesized and evaluated to optimize a prototype inhibitor of TGF-beta type I receptor kinase (ALK5), 6. Combination of replacement of a quinoxalin-6-yl moiety of 6 with a [1,2,4]triazolo[1,5-a]pyridin-6-yl moiety, insertion of a methyleneamino linker, and a o-F substituent in the phenyl ring markedly increased ALK5 inhibitory activity, kinase selectivity, and oral bioavailability. The 12b (EW-7197) inhibited ALKS with IC50 value of 0.013 mu M in a kinase assay and with IC50 values of 0.0165 and 0.0121 mu M in HaCaT (3TP-luc) stable cells and 4T1 (3TP-luc) stable cells, respectively, in a luciferase assay. Selectivity profiling of 12b using a panel of 320 protein kinases revealed that it is a highly selective ALKS/ALK4 inhibitor. Pharmacokinetic study with 12b center dot HCl in rats showed an oral bioavailability of 51% with high systemic exposure (AUC) of 1426 ng x h/mL and maximum plasma concentration (C-max) of 1620 ng/mL. Rational optimization of 6 has led to the identification of a highly potent, selective, and orally bioavailable ALK5 inhibitor 12b.
• INDOLE DERIVATIVES AS SOMATOSTATIN AGONISTS OR ANTAGONISTS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1562898A1

  公开（公告）日：2005-08-17
• 4-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazole and -pyrazole derivatives as potent and selective inhibitors of transforming growth factor-β type I receptor kinase
  作者：Cheng Hua Jin、Maddeboina Krishnaiah、Domalapally Sreenu、Vura Bala Subrahmanyam、Hyun-Ju Park、So-Jung Park、Yhun Yhong Sheen、Dae-Kee Kim

  DOI：10.1016/j.bmc.2014.03.022

  日期：2014.5

  A series of 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazoles and -pyrazoles 14a-c, 15a-c, 16a, 16b, 19a-d, 21a, and 21b has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. Among them, the pyrazole derivative 21b inhibited ALK5 phosphorylation with an IC50 value of 0.018 mu M and showed 95% inhibition at 0.03 mu M in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct. The 21b showed a high selectivity index of 284 against p38 alpha MAP kinase. The binding pose of 21b generated by docking analysis reveals that it fits well into the ATP binding cavity of ALK5 by forming several hydrogen bond interactions. (C) 2014 Elsevier Ltd. All rights reserved.