LCRF-0004 | 1229611-73-7

• 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: LCRF-0004
• 英文别名: N-(3-fluoro-4-((2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yl)oxy)phenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide；N-[3-fluoro-4-[2-(1-methylimidazol-4-yl)thieno[3,2-b]pyridin-7-yl]oxyphenyl]-1-phenyl-5-(trifluoromethyl)pyrazole-4-carboxamide
• CAS: 1229611-73-7
• 化学式: C₂₈H₁₈F₄N₆O₂S
• 分子量: 578.55
• InChiKey: DVRMYRDLCLUXQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  41
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  LCRF-0004 、 碘甲烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 ET007-059
  参考文献：
  名称：

  Design and synthesis of close analogs of LCRF-0004, a potent and selective RON receptor tyrosine kinase inhibitor

  摘要：

  New carboxamide head group analogs of thieno[3,2-b] pyridine-based kinase inhibitor LCRF-0004 were designed and synthesized. Potent and selective inhibitors of RON enzyme versus c-Met RTK were obtained. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.04.056
• 作为产物：
  描述：

  3-fluoro-4-(2-(1-methyl-1H-imidazol-4-yl)thienthio[3,2-b]pyridine-7-oxy)aniline 、 1-苯基-5-三氟甲基-1H-吡唑-4-羧酸 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 LCRF-0004
  参考文献：
  名称：

  Identification of a novel series of potent RON receptor tyrosine kinase inhibitors

  摘要：

  A novel series of N-(3-fluoro-4-(2-substituted-thieno[3,2-b]pyridin-7-yloxy) phenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamides targeting RON receptor tyrosine kinase was designed and synthesized. SAR study of the series allowed us to identify compounds possessing either inhibitory activity of RON kinase enzyme in the low nanomolar range with low residual activity against the closely related c-Met or potent dual inhibitory activity against RON and c-Met, - with no significant activity against VEGFR2 in both cases. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.03.073

文献信息

• INHIBITORS OF PROTEIN TYROSINE KINASE ACTIVITY
  申请人：Saavedra Mario Oscar

  公开号：US20080064718A1

  公开（公告）日：2008-03-13

  This invention relates to compounds that inhibit protein tyrosine kinase activity. In particular the invention relates to compounds that inhibit the protein tyrosine kinase activity of growth factor receptors, resulting in the inhibition of receptor signaling, for example, the inhibition of VEGF receptor signaling and HGF receptor signaling. More particularly, the invention relates to compounds, compositions and methods for the inhibition of VEGF receptor signaling and HGF receptor signaling. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

  本发明涉及抑制蛋白酪氨酸激酶活性的化合物。特别是，本发明涉及抑制生长因子受体蛋白酪氨酸激酶活性的化合物，从而抑制受体信号传导，例如抑制VEGF受体信号和HGF受体信号的传导。更具体地，本发明涉及用于抑制VEGF受体信号和HGF受体信号的化合物、组合物和方法。本发明还提供了用于治疗细胞增殖性疾病和病状的组合物和方法。
• [EN] METHODS AND COMPOSITIONS FOR TREATING CANCER<br/>[FR] MÉTHODES ET COMPOSITIONS DE TRAITEMENT DU CANCER
  申请人：ENGINE BIOSCIENCES PTE LTD

  公开号：WO2021126995A1

  公开（公告）日：2021-06-24

  The present disclosure provides lethal gene pair targets for cancer treatment, along with methods and compositions for regulating their expression and activity. Gene pairs disclosed herein include tyrosine kinase genes (e.g., SRC, RON, and YES). Also provided are methods and compositions for regulating tyrosine kinase activity, including RON specific pyrazole benzamide inhibitors and methods for gene regulation.
• Design and synthesis of close analogs of LCRF-0004, a potent and selective RON receptor tyrosine kinase inhibitor
  作者：Stéphane L. Raeppel、Franck Raeppel、Eric Therrien

  DOI：10.1016/j.bmcl.2015.04.056

  日期：2015.6

  New carboxamide head group analogs of thieno[3,2-b] pyridine-based kinase inhibitor LCRF-0004 were designed and synthesized. Potent and selective inhibitors of RON enzyme versus c-Met RTK were obtained. (C) 2015 Elsevier Ltd. All rights reserved.
• Identification of a novel series of potent RON receptor tyrosine kinase inhibitors
  作者：Stéphane Raeppel、Frédéric Gaudette、Michael Mannion、Stephen Claridge、Oscar Saavedra、Ljubomir Isakovic、Robert Déziel、Normand Beaulieu、Carole Beaulieu、Isabelle Dupont、Hannah Nguyen、James Wang、A. Robert Macleod、Christiane Maroun、Jeffrey M. Besterman、Arkadii Vaisburg

  DOI：10.1016/j.bmcl.2010.03.073

  日期：2010.5

  A novel series of N-(3-fluoro-4-(2-substituted-thieno[3,2-b]pyridin-7-yloxy) phenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxamides targeting RON receptor tyrosine kinase was designed and synthesized. SAR study of the series allowed us to identify compounds possessing either inhibitory activity of RON kinase enzyme in the low nanomolar range with low residual activity against the closely related c-Met or potent dual inhibitory activity against RON and c-Met, - with no significant activity against VEGFR2 in both cases. (C) 2010 Elsevier Ltd. All rights reserved.