3-fluoro-2-oxo-1-phenylpyrrolidine-3-carboxylic acid | 1361572-88-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 3-fluoro-2-oxo-1-phenylpyrrolidine-3-carboxylic acid
• 英文别名: 3-Fluoro-2-oxo-1-phenylpyrrolidine-3-carboxylic acid
• CAS: 1361572-88-4
• 化学式: C₁₁H₁₀FNO₃
• 分子量: 223.204
• InChiKey: JRRMIHSWVATMGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-fluoro-2-oxo-1-phenylpyrrolidine-3-carboxylic acid 、 4-[(6,7-dimethoxyquinolin-4-yl)oxy]-3-fluoroaniline 在 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， 以91%的产率得到N-(4-((6,7-dimethoxynaphthalen-1-yl)oxy)-3-fluorophenyl)-3-fluoro-2-oxo-1-phenylpyrrolidine-3-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
• 作为产物：
  描述：

  methyl 3-fluoro-2-oxo-1-phenylpyrrolidine-3-carboxylate 在 甲醇 、 potassium hydroxide 作用下， 反应 4.0h， 生成 3-fluoro-2-oxo-1-phenylpyrrolidine-3-carboxylic acid
  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

• PYRROLIDINONES AS METAP-2 INHIBITORS
  申请人：Heinrich Timo

  公开号：US20130296274A1

  公开（公告）日：2013-11-07

  Compounds of the formula I in which R 1 , R 2 , R 3 and R 4 have the meanings indicated in Claim 1 , are inhibitors of methionine aminopeptidase and can be employed for the treatment of tumours.

  公式I中，R1、R2、R3和R4的含义如权利要求1所示的化合物是蛋氨酸氨肽酶的抑制剂，可用于治疗肿瘤。
• PYRROLIDINONE ALS METAP-2 INHIBITOREN
  申请人：Merck Patent GmbH

  公开号：EP2627631B1

  公开（公告）日：2015-12-16
• US8895535B2
  申请人：——

  公开号：US8895535B2

  公开（公告）日：2014-11-25
• 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.