(S)-1-(2-(2,3-dihydro-1,4-benzodioxin-6-ylamino)-4-pyrimidinyl)-N-(4-methylbenzyl)-3-piperidinecarboxamide | 1347757-29-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: (S)-1-(2-(2,3-dihydro-1,4-benzodioxin-6-ylamino)-4-pyrimidinyl)-N-(4-methylbenzyl)-3-piperidinecarboxamide
• 英文别名: (S)-1-(2-(2,3-dihydrobenzo[B][1,4]dioxin-6-ylamino)pyrimidin-4-yl)-N-(4-methylbenzyl)piperidine-3-carboxamide；(3S)-1-[2-(2,3-dihydro-1,4-benzodioxin-6-ylamino)pyrimidin-4-yl]-N-[(4-methylphenyl)methyl]piperidine-3-carboxamide
• CAS: 1347757-29-2
• 化学式: C₂₆H₂₉N₅O₃
• 分子量: 459.548
• InChiKey: UIISEQIERCJOIL-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  88.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (S)-tert-butyl 3-(4-methylbenzylcarbamoyl)piperidine-1-carboxylate 在 盐酸 、 三乙胺 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 56.0h， 生成 (S)-1-(2-(2,3-dihydro-1,4-benzodioxin-6-ylamino)-4-pyrimidinyl)-N-(4-methylbenzyl)-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

• [EN] PYRIMIDINE COMPOUNDS THAT INHIBIT ANAPLASTIC LYMPHOMA KINASE<br/>[FR] COMPOSÉS PYRIMIDINE QUI INHIBENT LA KINASE DU LYMPHOME ANAPLASIQUE
  申请人：AMGEN INC

  公开号：WO2011143033A1

  公开（公告）日：2011-11-17

  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.

  Formula I的化合物是一种有用的间变性淋巴瘤激酶抑制剂。Formula I的化合物具有以下结构：变量的定义在此提供。
• 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。
• Pyrimidine compounds that inhibit anaplastic lymphoma kinase
  申请人：Bryan Marian C.

  公开号：US08716281B2

  公开（公告）日：2014-05-06

  The present invention describes pyrimidine compounds of Formula I that are useful as anaplastic lymphoma kinase inhibitors, pharmaceutically acceptable compositions thereof, and methods of using the same.

  本发明描述了公式I的嘧啶化合物，它们可用作间变性淋巴瘤激酶抑制剂，其药学上可接受的组合物以及使用它们的方法。
• US8716281B2
  申请人：——

  公开号：US8716281B2

  公开（公告）日：2014-05-06
• Rapid Development of Piperidine Carboxamides as Potent and Selective Anaplastic Lymphoma Kinase Inhibitors
  作者：Marian C. Bryan、Douglas A. Whittington、Elizabeth M. Doherty、James R. Falsey、Alan C. Cheng、Renee Emkey、Rachael L. Brake、Richard T. Lewis

  DOI：10.1021/jm201565s

  日期：2012.2.23

  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.