2-[3-(4-fluoro-benzyl)-3H-imidazo[4,5-b]pyridin-2-ylmethyl]-isoindole-1,3-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-[3-(4-fluoro-benzyl)-3H-imidazo[4,5-b]pyridin-2-ylmethyl]-isoindole-1,3-dione
• 英文别名: 2-{[3-(4-fluorobenzyl)-3H-imidazo[4,5-b]pyridin-2-yl]methyl}-1H-isoindole-1,3(2H)-dione；2-[[3-[(4-fluorophenyl)methyl]imidazo[4,5-b]pyridin-2-yl]methyl]isoindole-1,3-dione
• 化学式: C₂₂H₁₅FN₄O₂
• 分子量: 386.385
• InChiKey: NUCSQXWJTMYRMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  68.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[3-(4-fluoro-benzyl)-3H-imidazo[4,5-b]pyridin-2-ylmethyl]-isoindole-1,3-dione 在 一水合肼 作用下， 以 乙醇 为溶剂， 以97%的产率得到[3-[(4-Fluorophenyl)methyl]imidazo[4,5-b]pyridin-2-yl]methanamine
  参考文献：
  名称：

  [EN] AUTOTAXIN INHIBITORY COMPOUNDS
  [FR] COMPOSÉS INHIBITEURS DE L'AUTOTAXINE

  摘要：

  本发明涉及式I的化合物，其中A1、A2、A3、R1、R2、R3、R4、R5、R6、L、Ar和Q分别如本文所定义。本发明的化合物是自体脂肪酶（ATX）酶活性的抑制剂。本发明还涉及制备这些化合物的方法，包括含有它们的药物组合物，以及它们在治疗增殖性疾病（如癌症）以及其他ATX活性所涉及的疾病或症状（例如纤维化）中的用途。

  公开号：

  WO2016124939A1
• 作为产物：
  描述：

  N²-<(4-fluorophenyl)methyl>-2,3-pyridinamine 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 27.0h， 生成 2-[3-(4-fluoro-benzyl)-3H-imidazo[4,5-b]pyridin-2-ylmethyl]-isoindole-1,3-dione
  参考文献：
  名称：

  [EN] AUTOTAXIN INHIBITORY COMPOUNDS
  [FR] COMPOSÉS INHIBITEURS DE L'AUTOTAXINE

  摘要：

  本发明涉及式I的化合物，其中A1、A2、A3、R1、R2、R3、R4、R5、R6、L、Ar和Q分别如本文所定义。本发明的化合物是自体脂肪酶（ATX）酶活性的抑制剂。本发明还涉及制备这些化合物的方法，包括含有它们的药物组合物，以及它们在治疗增殖性疾病（如癌症）以及其他ATX活性所涉及的疾病或症状（例如纤维化）中的用途。

  公开号：

  WO2016124939A1

文献信息

• [EN] AUTOTAXIN INHIBITORY COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS DE L'AUTOTAXINE
  申请人：CANCER REC TECH LTD

  公开号：WO2016124939A1

  公开（公告）日：2016-08-11

  The present invention relates to compounds of formula I, wherein A1, A2, A3, R1, R2, R3, R4, R5, R6, L, Ar and Q are each as defined herein. The compounds of the present invention are inhibitors of autotaxin (ATX) enzyme activity. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions (e.g. fibrosis) in which ATX activity is implicated.

  本发明涉及式I的化合物，其中A1、A2、A3、R1、R2、R3、R4、R5、R6、L、Ar和Q分别如本文所定义。本发明的化合物是自体脂肪酶（ATX）酶活性的抑制剂。本发明还涉及制备这些化合物的方法，包括含有它们的药物组合物，以及它们在治疗增殖性疾病（如癌症）以及其他ATX活性所涉及的疾病或症状（例如纤维化）中的用途。
• Autotaxin inhibitory compounds
  申请人：CANCER RESEARCH TECHNOLOGY LIMITED

  公开号：US10654846B2

  公开（公告）日：2020-05-19

  The present invention relates to compounds of formula I, wherein A1, A2, A3, R1, R2, R3, R4, R5, R6, L, Ar and Q are each as defined herein. The compounds of the present invention are inhibitors of autotaxin (ATX) enzyme activity. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions (e.g. fibrosis) in which ATX activity is implicated.

  本发明涉及式 I 的化合物，其中 A1、A2、A3、R1、R2、R3、R4、R5、R6、L、Ar 和 Q 各如本文所定义。本发明的化合物是自体免疫球蛋白（ATX）酶活性的抑制剂。本发明还涉及制备这些化合物的工艺、包含这些化合物的药物组合物，以及它们在治疗增殖性疾病（如癌症）和其他涉及 ATX 活性的疾病或病症（如纤维化）中的用途。
• AUTOTAXIN INHIBITORY COMPOUNDS
  申请人：CANCER RESEARCH TECHNOLOGY LIMITED

  公开号：US20180016274A1

  公开（公告）日：2018-01-18

  The present invention relates to compounds of formula I, wherein A 1 , A 2 , A 3 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , L, Ar and Q are each as defined herein. The compounds of the present invention are inhibitors of autotaxin (ATX) enzyme activity. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions (e.g. fibrosis) in which ATX activity is implicated.
• Autotaxin Inhibitory Compunds
  申请人：Cancer Research Technology Limited

  公开号：US20200283435A1

  公开（公告）日：2020-09-10

  The present invention relates to compounds of formula I wherein A 1 , A 2 , A 3 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , L, Ar and Q are each as defined herein. The compounds of the present invention are inhibitors of autotaxin (ATX) enzyme activity. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions (e.g. fibrosis) in which ATX activity is implicated.
• Discovery of potent inhibitors of the lyso phospholipase autotaxin
  作者：Pritom Shah、Anne Cheasty、Caroline Foxton、Tony Raynham、Muddasar Farooq、Irene Farre Gutierrez、Aurore Lejeune、Michelle Pritchard、Andrew Turnbull、Leon Pang、Paul Owen、Susan Boyd、Alexandra Stowell、Allan Jordan、Niall M. Hamilton、James R. Hitchin、Martin Stockley、Ellen MacDonald、Mar Jimenez Quesada、Elisabeth Trivier、Jana Skeete、Huib Ovaa、Wouter H. Moolenaar、Hamish Ryder

  DOI：10.1016/j.bmcl.2016.10.036

  日期：2016.11

  The autotaxin-lysophosphatidic acid (ATX-LPA) axis has been implicated in several disease conditions including inflammation, fibrosis and cancer. This makes ATX an attractive drug target and its inhibition may lead to useful therapeutic agents. Through a high throughput screen (HTS) we identified a series of small molecule inhibitors of ATX which have subsequently been optimized for potency, selectivity and developability properties. This has delivered drug-like compounds such as 9v (CRT0273750) which modulate LPA levels in plasma and are suitable for in vivo studies.)(Tray crystallography has revealed that these compounds have an unexpected binding mode in that they do not interact with the active site zinc ions but instead occupy the hydrophobic LPC pocket extending from the active site of ATX together with occupying the LPA 'exit' channel. (C) 2016 Elsevier Ltd. All rights reserved.