1-(2-fluoro-3-nitrophenyl)-N,N-dimethylmethanamine | 1352609-95-0

• 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: 1-(2-fluoro-3-nitrophenyl)-N,N-dimethylmethanamine
• CAS: 1352609-95-0
• 化学式: C₉H₁₁FN₂O₂
• 分子量: 198.197
• InChiKey: VNLQSPKJOYBTRS-UHFFFAOYSA-N

物化性质

• 沸点：
  269.2±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-(2-fluoro-3-nitrophenyl)-N,N-dimethylmethanamine 在 盐酸 、 铁粉 、 potassium carbonate 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以91%的产率得到3-((dimethylamino)methyl)-2-fluoroaniline
  参考文献：
  名称：

  2-pyridyl substituted imidazoles as therapeutic ALK5 and/or ALK4 inhibitors

  摘要：

  这项发明涉及取代基为2-吡啶基的咪唑类化合物，它们是转化生长因子-β（TGF-β）类型I受体（ALK5）和/或激活素类型I受体（ALK4）的抑制剂，以及其制备方法和在医学中的应用，具体用于治疗和预防由这些受体介导的疾病状态。

  公开号：

  US08080568B1
• 作为产物：
  描述：

  2-氟-3-硝基苯甲酸 在 硼烷四氢呋喃络合物 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 1-(2-fluoro-3-nitrophenyl)-N,N-dimethylmethanamine
  参考文献：
  名称：

  [EN] IMINOTETRAHYDROPYRIMIDINONE DERIVATIVES AS PLASMEPSIN V INHIBITORS
  [FR] DÉRIVÉS D'IMINOTÉTRAHYDROPYRIMIDINONE UTILISÉS COMME INHIBITEURS DE PLASMEPSINE V

  摘要：

  一系列在6-位置被苯基取代的2-亚氨基-6-甲基四氢嘧啶-4(1H)-酮衍生物，该苯基再通过一个可选取代的不饱和融合双环环系统进行间位取代，该环系统含有至少一个氮原子，作为血液型质体蛋白酶V活性的选择性抑制剂，对于药物制剂特别有益，尤其在治疗疟疾方面。

  公开号：

  WO2017089453A1

文献信息

• 2-PYRIDYL SUBSTITUTED IMIDAZOLES AS THERAPEUTIC ALK5 AND/OR ALK4 INHIBITORS
  申请人：Kim Dae-Kee

  公开号：US20110319406A1

  公开（公告）日：2011-12-29

  This invention relates to 2-pyridyl substituted imidazoles which are inhibitors of the transforming growth factor-β (TGF-β) type I receptor (ALK5) and/or the activin type I receptor (ALK4), methods for their preparation, and their use in medicine, specifically in the treatment and prevention of a disease state mediated by these receptors.

  本发明涉及2-吡啶基取代咪唑类化合物，其为转化生长因子-β（TGF-β）类型I受体（ALK5）和/或激活素类型I受体（ALK4）的抑制剂，以及其制备方法和在医学上的应用，特别是用于治疗和预防由这些受体介导的疾病状态。
• 2-Pyridyl substituted imidazoles as therapeutic Alk5 and/or Alk4 inhibitors
  申请人：Ewha University-Industry Collaboration Foundation

  公开号：EP2947081A1

  公开（公告）日：2015-11-25

  This invention relates to 2-pyridyl substituted imidazoles (I) which are inhibitors of the transforming growth factor-β (TGF-β) type I receptor (ALK5) and/or the activin type I receptor (ALK4), methods for their preparation, and their use in medicine, specifically in the treatment and prevention of a disease state mediated by these receptors.

  本发明涉及作为转化生长因子-β（TGF-β）Ⅰ型受体（ALK5）和/或激活素Ⅰ型受体（ALK4）抑制剂的 2-吡啶基取代的咪唑（I）、其制备方法及其在医学中的用途，特别是在治疗和预防由这些受体介导的疾病状态中的用途。
• Iminotetrahydropyrimidinone derivatives as plasmepsin V inhibitors
  申请人：UCB Biopharma SPRL

  公开号：US11136310B2

  公开（公告）日：2021-10-05

  A series of 2-imino-6-methyltetrahydropyrimidin-4(1H)-one derivatives, substituted in the 6-position by a phenyl moiety which in turn is meta-substituted by an optionally substituted unsaturated fused bicyclic ring system containing at least one nitrogen atom, being selective inhibitors of plasmepsin V activity, are beneficial as pharmaceutical agents, especially in the treatment of malaria.

  一系列 2-亚氨基-6-甲基四氢嘧啶-4(1H)-酮衍生物，在 6 位被苯基取代，而苯基又被含有至少一个氮原子的任选取代的不饱和融合双环体系元取代，是胰蛋白酶 V 活性的选择性抑制剂，可用作药物，特别是治疗疟疾。
• 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.
• 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.