2-amino-N-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-5-(2-oxo-1,3-dihydroindol-5-yl)pyridine-3-carboxamide | 1394930-25-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-amino-N-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-5-(2-oxo-1,3-dihydroindol-5-yl)pyridine-3-carboxamide
• CAS: 1394930-25-6
• 化学式: C₂₂H₁₇Cl₂FN₄O₂
• 分子量: 459.307
• InChiKey: YXLSVZWTQLJCDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  97.1
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基烟酸 在 四(三苯基膦)钯 、 potassium fluoride dihydrate 、 溴 、 溶剂黄146 、 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 乙二醇二甲醚 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.33h， 生成 2-amino-N-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-5-(2-oxo-1,3-dihydroindol-5-yl)pyridine-3-carboxamide
  参考文献：
  名称：

  Discovery of novel 2-aminopyridine-3-carboxamides as c-Met kinase inhibitors

  摘要：

  A series of 2-aminopyridine-3-carboxamide derivatives against c-Met were designed and synthesized by employing bioisosteric replacement of heterocyclic moieties with the amide bond. The structure-activity relationship (SAR) at various positions of the scaffold was explored. In this study, a promising compound (S)-24o with a c-Met IC50 of 0.022 mu M was identified. The compound exhibited dose-dependent inhibition of the phosphorylation of c-Met as well as downstream signaling in EBC-1 cells. Furthermore, the interactive binding model of (S)-24o with c-Met was elucidated by virtue of a molecular modeling study. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.007

文献信息

• [EN] NEW AMINOPYRIDINE COMPOUNDS, THE PREPARATION METHOD, THE PHARMACEUTICAL COMPOSITIONS COMPRISING THESE COMPOUNDS AND THE USES THEREOF<br/>[FR] NOUVEAUX COMPOSÉS D'AMINOPYRIDINE, LE PROCÉDÉ DE PRÉPARATION, LES COMPOSITIONS PHARMACEUTIQUES COMPRENANT CES COMPOSÉS ET LES UTILISATIONS DE CEUX-CI
  申请人：SHANGHAI INST MATERIA MEDICA

  公开号：WO2012129967A1

  公开（公告）日：2012-10-04

  本发明涉及药物化学和药物治疗学领域，具体涉及作为受体酪氨酸激酶MET抑制剂的通式I的化合物，其对映异构体、非对映异构体、外消旋体及其混合物或其可药用的盐，其制备方法、含此类化合物的药物组合物及用途。
• Discovery of novel 2-aminopyridine-3-carboxamides as c-Met kinase inhibitors
  作者：Dengyou Zhang、Jing Ai、Zhongjie Liang、Chunpu Li、Xia Peng、YinChun Ji、Hualiang Jiang、Meiyu Geng、Cheng Luo、Hong Liu

  DOI：10.1016/j.bmc.2012.07.007

  日期：2012.9

  A series of 2-aminopyridine-3-carboxamide derivatives against c-Met were designed and synthesized by employing bioisosteric replacement of heterocyclic moieties with the amide bond. The structure-activity relationship (SAR) at various positions of the scaffold was explored. In this study, a promising compound (S)-24o with a c-Met IC50 of 0.022 mu M was identified. The compound exhibited dose-dependent inhibition of the phosphorylation of c-Met as well as downstream signaling in EBC-1 cells. Furthermore, the interactive binding model of (S)-24o with c-Met was elucidated by virtue of a molecular modeling study. (C) 2012 Elsevier Ltd. All rights reserved.