6-(2-(dimethoxymethyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine | 1352609-89-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并吡啶类
• 英文名称: 6-(2-(dimethoxymethyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine
• 英文别名: 6-[2-(dimethoxymethyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl]-[1,2,4]triazolo[1,5-a]pyridine
• CAS: 1352609-89-2
• 化学式: C₁₈H₁₈N₆O₂
• 分子量: 350.38
• InChiKey: KXRJQMOWXOUNST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  90.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-(2-(dimethoxymethyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine 在 溶剂黄146 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 8.0h， 生成 ALK4/ALK5抑制剂
  参考文献：
  名称：

  双酮类化合物的制备方法和咪唑类衍生物的制备方法

  摘要：

  本公开提供一种双酮类化合物的制备方法和咪唑类衍生物的制备方法，属于医药技术领域。该双酮类化合物的制备方法无需采用氯化氧锆等对人有严重危害的化学品，降低了对人体和环境的危害。不仅如此，在制备过程中避免大量应用酸，避免产生大量酸性废水进而减少废水处理量并降低环境污染。

  公开号：

  CN114573576A
• 作为产物：
  描述：

  6-甲基-2-吡啶甲醛 在 ziconium(IV) oxychloride octahydrate 、 ammonium acetate 、 氢溴酸 、 caesium carbonate 、 二甲基亚砜 作用下， 以 四氢呋喃 、 甲醇 、 甲基叔丁基醚 、 水 、 异丙醇 为溶剂， 反应 7.0h， 生成 6-(2-(dimethoxymethyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine
  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

文献信息

• [EN] PYRIDINYLIMIDAZOLES<br/>[FR] PYRIDINYLIMIDAZOLES
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO2001062756A1

  公开（公告）日：2001-08-30

  Compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R1, R2 and R3 represent various functional groups, and one of X1 and X2 is N and the other is NR10; and their use as pharmaceuticals.

  公式（I）的化合物及其药学上可接受的盐，其中R1、R2和R3代表各种功能基团，X1和X2中的一个是N，另一个是NR10；以及它们作为药物的用途。
• 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。
• 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.