(S)-N-(3-methylbenzyl)-1-(2-((3,4,5-trimethoxyphenyl)amino)-4-pyrimidinyl)-3-piperidinecarboxamide | 1347756-41-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-N-(3-methylbenzyl)-1-(2-((3,4,5-trimethoxyphenyl)amino)-4-pyrimidinyl)-3-piperidinecarboxamide
• 英文别名: (3S)-N-[(3-methylphenyl)methyl]-1-[2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]piperidine-3-carboxamide
• CAS: 1347756-41-5
• 化学式: C₂₇H₃₃N₅O₄
• 分子量: 491.59
• InChiKey: OZNRQZFKHOJXCQ-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  97.8
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (S)-3-哌啶甲酸乙酯 在 lithium hydroxide monohydrate 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 二甲基亚砜 、 1,2-二氯乙烷 为溶剂， 反应 115.0h， 生成 (S)-N-(3-methylbenzyl)-1-(2-((3,4,5-trimethoxyphenyl)amino)-4-pyrimidinyl)-3-piperidinecarboxamide
  参考文献：
  名称：

  Rapid Development of Piperidine Carboxamides as Potent and Selective Anaplastic Lymphoma Kinase Inhibitors

  摘要：

  Piperidine carboxamide 1 was identified as a novel inhibitor of anaplastic lymphoma kinase (ALK enzyme assay IC50 = 0.174 mu M) during high throughput screening, with selectivity over the related kinase insulin-like growth factor-1 (IGF1R). The X-ray cocrystal structure of 1 with the ALK kinase domain revealed an unusual DFG-shifted conformation, allowing access to an extended hydrophobic pocket. Structure-activity relationship (SAR) studies were focused on the rapid parallel optimization of both the right- and left-hand side of the molecule, culminating in molecules with improved potency and selectivity over IGF1R.

  DOI：

  10.1021/jm201565s

文献信息

• PYRIMIDINE COMPOUNDS THAT INHIBIT ANAPLASTIC LYMPHOMA KINASE
  申请人：Bryan Marian C.

  公开号：US20130158019A1

  公开（公告）日：2013-06-20

  Compounds of Formula I are useful inhibitors of anaplastic lymphoma kinase. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

  公式I的化合物是阻断无形淋巴瘤激酶的有用抑制剂。公式I的化合物具有以下结构：其中变量的定义在此提供。
• US8716281B2
  申请人：——

  公开号：US8716281B2

  公开（公告）日：2014-05-06