2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxylic acid | 1272758-11-8

• 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: 2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxylic acid
• 英文别名: 2-oxo-1-[3-(trifluoromethyl)phenyl]pyridine-3-carboxylic acid
• CAS: 1272758-11-8
• 化学式: C₁₃H₈F₃NO₃
• 分子量: 283.207
• InChiKey: KFEISZAWONWZCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxylic acid 、 N1-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)benzene-1,4-diamine 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 二氯甲烷 为溶剂， 反应 3.0h， 以84%的产率得到2-oxo-N-(4-(9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-ylamino)phenyl)-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-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
• 作为产物：
  描述：

  2-羟基烟酸 在 氯化亚砜 、 caesium carbonate 、 2-环己酮甲酸乙酯 、 copper(I) bromide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 37.0h， 生成 2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxylic acid
  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

• 2-PYRIDINE DERIVATIVES AS INHIBITORS OF NEUTROPHILE ELASTASE
  申请人：Brimert Thomas

  公开号：US20090105239A1

  公开（公告）日：2009-04-23

  The invention provides compounds of formula wherein R 1 , R 3 , R 4 , R 5 , R 6 , R 14 , X, W and Z are as defined in the specification and optical isomers, racemates and tautomers thereof, and pharmaceutically acceptable salts thereof; together with processes for their preparation, pharmaceutical compositions containing them and their use in therapy. The compounds are inhibitors of human neutrophil elastase.

  本发明提供了式中R1，R3，R4，R5，R6，R14，X，W和Z如规范中所定义的化合物及其光学异构体，外消旋体和互变异构体，以及其药学上可接受的盐；以及它们的制备方法，包含它们的制药组合物和它们在治疗中的应用。这些化合物是人类中性粒细胞弹性蛋白酶的抑制剂。