5-溴-1-甲基-4-氧代-1,4-二氢吡啶-3-羧酸甲酯 | 1052114-84-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 5-溴-1-甲基-4-氧代-1,4-二氢吡啶-3-羧酸甲酯
• 英文名称: methyl 5-bromo-1-methyl-4-oxo-1,4-dihydropyridine-3-carboxylate
• 英文别名: methyl 5-bromo-1-methyl-4-oxopyridine-3-carboxylate
• CAS: 1052114-84-7
• 化学式: C₈H₈BrNO₃
• 分子量: 246.06
• InChiKey: WONREHDSAPUCDS-UHFFFAOYSA-N

物化性质

• 沸点：
  296.5±40.0 °C(Predicted)
• 密度：
  1.656±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-溴-1-甲基-4-氧代-1,4-二氢吡啶-3-羧酸甲酯 在 四(三苯基膦)钯 、 sodium carbonate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 N-(5-((6,7-dimethoxyquinolin-4-yl)oxy)pyridin-2-yl)-5-(4-fluorophenyl)-1-methyl-4-oxo-1,4-dihydropyridine-3-carboxamide
  参考文献：
  名称：

  [EN] QUINOLINE COMPOUNDS AS INHIBITORS OF TAM AND MET KINASES
  [FR] COMPOSÉS DE QUINOLÉINE UTILISÉS EN TANT QU'INHIBITEURS DE KINASES TAM ET MET

  摘要：

  本文提供的是Formula (I)的化合物或其药用盐，其中X1、X2、X3、R1、R2、R3、R4、R5、R6和R7的定义如本文所述，这些化合物是一种或多种TAM激酶和/或c-Met激酶的抑制剂，可用于治疗和预防可以用TAM激酶抑制剂和/或c-Met激酶抑制剂治疗的疾病。

  公开号：

  WO2020141470A1
• 作为产物：
  描述：

  5-溴-4-羟基吡啶-3-甲酸 、 碘甲烷 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.33h， 以86%的产率得到5-溴-1-甲基-4-氧代-1,4-二氢吡啶-3-羧酸甲酯
  参考文献：
  名称：

  Discovery of Pyrrolopyridine−Pyridone Based Inhibitors of Met Kinase: Synthesis, X-ray Crystallographic Analysis, and Biological Activities

  摘要：

  Conformationally constrained 2-pyridone analogue 2 is a potent Met kinase inhibitor with an IC(50) value of 1.8 nM. Further SAR of the 2-pyridone based inhibitors of Met kinase led to potent 4-pyridone and pyridine N-oxide inhibitors Such as 3 and 4. The X-ray crystallographic data of the inhibitor 2 bound to the ATP binding site of Met kinase protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues showed potent anti proliferative activities against the Met dependent GTL-16 gastric carcinoma cell line. Compound 2 also inhibited Flt-3 and VEGFR-2 kinases with IC(50) values of 4 and 27 nM, respectively. It possesses a favorable pharmacokinetic profile in mice and demonstrates significant in vivo antitumor activity in the GTI-16 human gastric carcinoma xenograft model.

  DOI：

  10.1021/jm800476q

文献信息

• [EN] PYRAZOLO[3,4-b]PYRIDINE COMPOUNDS AS INHIBITORS OF TAM AND MET KINASES<br/>[FR] COMPOSÉS PYRAZOLO[3,4-B]PYRIDINE UTILISÉS EN TANT QU'INHIBITEURS DE KINASES TAM ET MET
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2020047184A1

  公开（公告）日：2020-03-05

  Provided herein are compounds of the Formula (I): and stereoisomers, tautomers and pharmaceutically acceptable salts thereof, wherein R1, R2, R9, X1 and G are as defined herein, which are inhibitors of one or more TAM kinases and/or c-Met kinase, and are useful in the treatment and prevention of diseases which can be treated with a TAM kinase inhibitor and/or a c-Met kinase inhibitor.

  本文提供了Formula (I)的化合物及其立体异构体、互变异构体和药学上可接受的盐，其中R1、R2、R9、X1和G如本文所定义，它们是一种或多种TAM激酶和/或c-Met激酶的抑制剂，并且在治疗和预防可以用TAM激酶抑制剂和/或c-Met激酶抑制剂治疗的疾病中非常有用。
• PYRAZOLO[3,4-B]PYRIDINE COMPOUNDS AS INHIBITORS OF TAM AND MET KINASES
  申请人：Array BioPharma Inc.

  公开号：EP3843850A1

  公开（公告）日：2021-07-07
• QUINOLINE COMPOUNDS AS INHIBITORS OF TAM AND MET KINASES
  申请人：Array BioPharma Inc.

  公开号：EP3906234A1

  公开（公告）日：2021-11-10
• PYRAZOLO[3,4-b]PYRIDINE COMPOUNDS AS INHIBITORS OF TAM AND MET KINASES
  申请人：Array BioPharma Inc.

  公开号：US20200079770A1

  公开（公告）日：2020-03-12

  Provided herein are compounds of the Formula I: and stereoisomers, tautomers and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 9 , X 1 and G are as defined herein, which are inhibitors of one or more TAM kinases and/or c-Met kinase, and are useful in the treatment and prevention of diseases which can be treated with a TAM kinase inhibitor and/or a c-Met kinase inhibitor.