1-(4-fluorophenyl)-N-[3-fluoro-4-(7H-purin-6-ylamino)phenyl]-2-oxopyridine-3-carboxamide | 1428155-41-2

• 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-fluorophenyl)-N-[3-fluoro-4-(7H-purin-6-ylamino)phenyl]-2-oxopyridine-3-carboxamide
• CAS: 1428155-41-2
• 化学式: C₂₃H₁₅F₂N₇O₂
• 分子量: 459.415
• InChiKey: BBFKYIGXPPTHCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-羟基烟酸 在 氯化亚砜 、 caesium carbonate 、 N,N-二异丙基乙胺 、 2-环己酮甲酸乙酯 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 、 copper(I) bromide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 44.0h， 生成 1-(4-fluorophenyl)-N-[3-fluoro-4-(7H-purin-6-ylamino)phenyl]-2-oxopyridine-3-carboxamide
  参考文献：
  名称：

  Inhibitors of the TAM subfamily of tyrosine kinases: Synthesis and biological evaluation

  摘要：

  The TAM subfamily of Receptor Tyrosine Kinases (RTKs) contains three human proteins of therapeutical interest, Axl, Mer, and Tyro3. Our goal was to design a type II inhibitor specific for this family, i.e. able to interact with the allosteric pocket and with the hinge region of the kinase. We report the synthesis of several series of purine analogues of BMS-777607. The structural diversity of the designed inhibitors was expected to modify the interactions formed in the binding site and consequently to modulate their selectivity profiles. The most potent inhibitor 6g exhibits K(d)s of 39, 42, 65 and 200 nM against Axl, Mer, Met and Tyro3 respectively. Analysis of the affinity of 6g for active and inactive forms of Abl1, an RTK protein that does not belong to the TAM subfamily, together with the binding modes of 6g predicted by docking studies, indicates that 6g displays some selectivity for the TAM family and may act as a type II inhibitor. Crown Copyright (C) 2012 Published by Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.005

文献信息

• MERTK DEGRADERS AND USES THEREOF
  申请人：Kymera Therapeutics, Inc.

  公开号：US20220356185A1

  公开（公告）日：2022-11-10

  The present invention provides compounds, compositions thereof, and methods of using the same.
• [EN] MERTK DEGRADERS AND USES THEREOF<br/>[FR] AGENTS DE DÉGRADATION DE MERTK ET LEURS UTILISATIONS
  申请人：KYMERA THERAPEUTICS INC

  公开号：WO2021011871A1

  公开（公告）日：2021-01-21

  The present invention provides compounds, compositions thereof, and methods of using the same.
• Inhibitors of the TAM subfamily of tyrosine kinases: Synthesis and biological evaluation
  作者：Rosa M. Suárez、Franciane Chevot、Andrea Cavagnino、Nicolas Saettel、François Radvanyi、Sandrine Piguel、Isabelle Bernard-Pierrot、Véronique Stoven、Michel Legraverend

  DOI：10.1016/j.ejmech.2012.06.005

  日期：2013.3

  The TAM subfamily of Receptor Tyrosine Kinases (RTKs) contains three human proteins of therapeutical interest, Axl, Mer, and Tyro3. Our goal was to design a type II inhibitor specific for this family, i.e. able to interact with the allosteric pocket and with the hinge region of the kinase. We report the synthesis of several series of purine analogues of BMS-777607. The structural diversity of the designed inhibitors was expected to modify the interactions formed in the binding site and consequently to modulate their selectivity profiles. The most potent inhibitor 6g exhibits K(d)s of 39, 42, 65 and 200 nM against Axl, Mer, Met and Tyro3 respectively. Analysis of the affinity of 6g for active and inactive forms of Abl1, an RTK protein that does not belong to the TAM subfamily, together with the binding modes of 6g predicted by docking studies, indicates that 6g displays some selectivity for the TAM family and may act as a type II inhibitor. Crown Copyright (C) 2012 Published by Elsevier Masson SAS. All rights reserved.