2-amino-N-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridine-3-carboxamide | 1394930-19-8

• 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: 2-amino-N-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridine-3-carboxamide
• 英文别名: 2-amino-N-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridine-3-carboxamide
• CAS: 1394930-19-8
• 化学式: C₂₂H₂₃Cl₂FN₆O
• 分子量: 477.369
• InChiKey: UAAGAPAGCIEIPW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  97.9
• 氢给体数：
  3
• 氢受体数：
  6

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-) 、 三氟乙酸 作用下， 以 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.33h， 生成 2-amino-N-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-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

• Synthesis and biological evaluation of 2-amino-5-aryl-3-benzylthiopyridine scaffold based potent c-Met inhibitors
  作者：Dengyou Zhang、Xiaowei Zhang、Jing Ai、Yun Zhai、Zhongjie Liang、Ying Wang、Yi Chen、Chunpu Li、Fei Zhao、Hualiang Jiang、Meiyu Geng、Cheng Luo、Hong Liu

  DOI：10.1016/j.bmc.2013.07.032

  日期：2013.11

  2-amino-3-benzylthiopyridines against c-Met were designed by means of bioisosteric replacement and docking analysis. Optimization of the 2-amino-3-benzylthiopyridine scaffold led to the identification of compound (R)-10b displaying c-Met inhibition with an IC50 up to 7.7 nM. In the cytotoxic evaluation, compound (R)-10b effectively inhibited the proliferation of c-Met addictive human cancer cell lines

  一系列的2-氨基Ñ -benzylpyridine -3- carboxnamides，2-氨基Ñ针对c-Met的-benzylpyridine -3-磺酰胺和2-氨基-3- benzylthiopyridines通过生物电子等排更换和对接分析来设计。对2-氨基-3-苄基硫代吡啶骨架的优化导致鉴定化合物（R）-10b，其显示出c-Met抑制，IC 50高达7.7 nM。在细胞毒性评估中，化合物（R）-10b有效抑制c-Met上瘾的人类癌细胞系的增殖（IC 50从0.19到0.71μM）和c-Met激活介导的细胞转移。在100 mg / Kg的剂量下，（R）-10b明显抑制了NIH-3T3 / TPR-Met异种移植模型中的肿瘤生长（45％）。值得注意的是，（R）-10b可以克服c-Met激活介导的吉非替尼耐药性，这表明其在药物组合中的潜在用途。综上所述，首先公开了2-氨基-3-苄基硫代吡啶
• [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.