7-(2-fluoro-4-iodo-phenylamino)-6-methyl-5-oxo-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid | 1150098-37-5

• 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
• 英文名称: 7-(2-fluoro-4-iodo-phenylamino)-6-methyl-5-oxo-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid
• 英文别名: 7-(2-Fluoro-4-iodophenylamino)-6-methyl-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylic acid；7-(2-fluoro-4-iodoanilino)-6-methyl-5-oxo-2,3-dihydro-1H-indolizine-8-carboxylic acid
• CAS: 1150098-37-5
• 化学式: C₁₆H₁₄FIN₂O₃
• 分子量: 428.202
• InChiKey: JDHMGQJGTAMMDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-(2-fluoro-4-iodo-phenylamino)-6-methyl-5-oxo-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 7-(2-Fluoro-4-iodo-phenylamino)-6-methyl-5-oxo-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid (2-hydroxy-ethoxy)-amide
  参考文献：
  名称：

  Design and synthesis of orally available MEK inhibitors with potent in vivo antitumor efficacy

  摘要：

  The structure-based design, synthesis, and biological evaluation of two novel series of potent and selective MEK kinase inhibitors are described herein. The elaboration of a lead pyrrole derivative to a bicyclic dihydroindolone core provided compounds with high potency and good drug-like pharmaceutical properties. Further scaffold modification afforded a series of dihydroindolizinone inhibitors, including an orally available advanced preclinical MEK inhibitor with potent in vivo antitumor efficacy. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.026
• 作为产物：
  描述：

  7-chloro-6-methyl-5-oxo-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid ethyl ester 在 甲醇 、 sodium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 生成 7-(2-fluoro-4-iodo-phenylamino)-6-methyl-5-oxo-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid
  参考文献：
  名称：

  Design and synthesis of orally available MEK inhibitors with potent in vivo antitumor efficacy

  摘要：

  The structure-based design, synthesis, and biological evaluation of two novel series of potent and selective MEK kinase inhibitors are described herein. The elaboration of a lead pyrrole derivative to a bicyclic dihydroindolone core provided compounds with high potency and good drug-like pharmaceutical properties. Further scaffold modification afforded a series of dihydroindolizinone inhibitors, including an orally available advanced preclinical MEK inhibitor with potent in vivo antitumor efficacy. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.026

文献信息

• Heterocyclic Compounds as MEK Inhibitors
  申请人：Chikkanna Dinesh

  公开号：US20090275606A1

  公开（公告）日：2009-11-05

  The present invention relates to compounds of formula I and pharmaceutically acceptable salts. These compounds can act as potential MEK inhibitors in the treatment of hyperproliferative diseases, like cancer and inflammation. The present invention also reveals methods of preparation thereof.

  本发明涉及公式I的化合物和药用盐。这些化合物可以作为潜在的MEK抑制剂，用于治疗癌症和炎症等过度增殖性疾病。本发明还揭示了其制备方法。
• MAPK/ERK KINASE INHIBITORS
  申请人：Adams MarK

  公开号：US20090124595A1

  公开（公告）日：2009-05-14

  Compounds of the following formula are provided for use with MEK: wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.

  提供以下公式的化合物供与甲酮使用：其中变量如本文所定义。还提供包含这些化合物的药物组合物、工具箱和制造物品；制备这些化合物有用的方法和中间体；以及使用这些化合物的方法。
• MAPK/ERK kinase inhibitors
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US08022057B2

  公开（公告）日：2011-09-20

  Compounds of the following formula are provided for use with MEK: wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.

  提供以下式子的化合物，用于与MEK配合使用：其中变量如此处所定义。同时提供包含此类化合物的药物组合物、套件和制造品；有用于制造此类化合物的中间体和方法；以及使用该类化合物的方法。
• US8022057B2
  申请人：——

  公开号：US8022057B2

  公开（公告）日：2011-09-20
• [EN] MAPK/ERK KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA MAPK/ERK KINASE
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2009064675A1

  公开（公告）日：2009-05-22

  Compounds of the following Formula (I) are provided for use with MEK: wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.