3-benzyl-N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-2-oxopyrrolidine-1-carboxamide | 1361573-13-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-benzyl-N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-2-oxopyrrolidine-1-carboxamide
• 英文别名: 3-benzyl-N-[4-(6,7-dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]-2-oxopyrrolidine-1-carboxamide
• CAS: 1361573-13-8
• 化学式: C₂₉H₂₆FN₃O₅
• 分子量: 515.541
• InChiKey: XNEDFTVHEMGHBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  90
• 氢给体数：
  1
• 氢受体数：
  7

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	4-[(6,7-dimethoxyquinolin-4-yl)oxy]-3-fluoroaniline	347161-74-4	C17H15FN2O3	314.316

反应信息

• 作为产物：
  描述：

  3-苄基吡咯烷-2-酮 在 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-benzyl-N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-2-oxopyrrolidine-1-carboxamide
  参考文献：
  名称：

  Structure-Based Design of Novel Class II c-Met Inhibitors: 1. Identification of Pyrazolone-Based Derivatives

  摘要：

  Deregulation of c-Met receptor tyrosine kinase activity leads to tumorigenesis and metastasis in animal models. More importantly, the identification of activating mutations in c-Met, as well as MET gene amplification in human cancers, points to c-Met as an important target for cancer therapy. We have previously described two classes of c-Met kinase inhibitors (class I and class II) that differ in their binding modes and selectivity profiles. The class II inhibitors tend to have activities on multiple kinases. Knowledge of the binding mode of these molecules in the c-Met protein led to the design and evaluation of several new class II c-Met inhibitors that utilize various 5-membered cyclic carboxamides to conformationally restrain key pharmacophoric groups within the molecule. These investigations resulted in the identification of a potent and novel class of pyrazolone c-Met inhibitors with good in vivo activity.

  DOI：

  10.1021/jm201330u

文献信息

• Structure-Based Design of Novel Class II c-Met Inhibitors: 1. Identification of Pyrazolone-Based Derivatives
  作者：Mark H. Norman、Longbin Liu、Matthew Lee、Ning Xi、Ingrid Fellows、Noel D. D’Angelo、Celia Dominguez、Karen Rex、Steven F. Bellon、Tae-Seong Kim、Isabelle Dussault

  DOI：10.1021/jm201330u

  日期：2012.3.8

  Deregulation of c-Met receptor tyrosine kinase activity leads to tumorigenesis and metastasis in animal models. More importantly, the identification of activating mutations in c-Met, as well as MET gene amplification in human cancers, points to c-Met as an important target for cancer therapy. We have previously described two classes of c-Met kinase inhibitors (class I and class II) that differ in their binding modes and selectivity profiles. The class II inhibitors tend to have activities on multiple kinases. Knowledge of the binding mode of these molecules in the c-Met protein led to the design and evaluation of several new class II c-Met inhibitors that utilize various 5-membered cyclic carboxamides to conformationally restrain key pharmacophoric groups within the molecule. These investigations resulted in the identification of a potent and novel class of pyrazolone c-Met inhibitors with good in vivo activity.