tert-butyl-3-(2-(4-(N-methylpropionamido)phenylamino)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-ylamino)piperidine-1-carboxylate | 1254783-88-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: tert-butyl-3-(2-(4-(N-methylpropionamido)phenylamino)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-ylamino)piperidine-1-carboxylate
• 英文别名: tert-butyl 3-[[2-[4-[methyl(propanoyl)amino]anilino]-9-(oxan-2-yl)purin-6-yl]amino]piperidine-1-carboxylate
• CAS: 1254783-88-4
• 化学式: C₃₀H₄₂N₈O₄
• 分子量: 578.715
• InChiKey: QTHIWAZLLASPLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl-3-(2-(4-(N-methylpropionamido)phenylamino)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-ylamino)piperidine-1-carboxylate 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 N-(4-(6-(1-acryloylpiperidin-3-ylamino)-9H-purin-2-ylamino)phenyl)-N-methylpropionamide
  参考文献：
  名称：

  Discovery of selective irreversible inhibitors for EGFR-T790M

  摘要：

  Targeting the epidermal growth factor receptor kinase (EGFR) with ATP-competitive kinase inhibitors results in dramatic but short-lived responses in patients with EGFR mutant non small cell lung cancer. A series of novel covalent EGFR kinase inhibitors with selectivity for the clinically relevant T790M 'gatekeeper' resistance mutation relative to wild-type EGFR were discovered by library screening. A representative compound 3i was obtained through a systematic SAR study guided by mutant EGFR-dependent cellular proliferation assays. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.036
• 作为产物：
  描述：

  4-硝基丙酰苯胺 在 tris-(dibenzylideneacetone)dipalladium(0) 、 10% palladium on activated charcoal 、 氢气 、 sodium hydride 、 sodium t-butanolate 、 1,3-双(2,6-二异丙基苯基)氯化咪唑鎓 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl-3-(2-(4-(N-methylpropionamido)phenylamino)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-ylamino)piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of selective irreversible inhibitors for EGFR-T790M

  摘要：

  Targeting the epidermal growth factor receptor kinase (EGFR) with ATP-competitive kinase inhibitors results in dramatic but short-lived responses in patients with EGFR mutant non small cell lung cancer. A series of novel covalent EGFR kinase inhibitors with selectivity for the clinically relevant T790M 'gatekeeper' resistance mutation relative to wild-type EGFR were discovered by library screening. A representative compound 3i was obtained through a systematic SAR study guided by mutant EGFR-dependent cellular proliferation assays. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.036

文献信息

• EGFR INHIBITORS AND METHODS OF TREATING DISORDERS
  申请人：Gray Nathanael S.

  公开号：US20120094999A1

  公开（公告）日：2012-04-19

  The present invention relates to novel pyrimidine, pyrrolo-pyrimidine, pyrrolo-pyridine, pyridine, purine and triazine compounds which are able to modulate epidermal growth factor receptor (EGFR), including Her-kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.

  本发明涉及新型嘧啶，吡咯嘧啶，吡咯吡啶，吡啶，嘌呤和三嗪化合物，这些化合物能够调控表皮生长因子受体（EGFR），包括Her-kinases，并且在治疗各种疾病，障碍或条件中使用这些化合物。
• [EN] EGFR INHIBITORS AND METHODS OF TREATING DISORDERS<br/>[FR] INHIBITEURS D'EGFR ET PROCÉDÉS DE TRAITEMENT DE TROUBLES
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2010129053A8

  公开（公告）日：2011-12-15
• EGFR Inhibitors and Methods of Treating Disorders
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US20190040065A1

  公开（公告）日：2019-02-07

  The present invention relates to novel pyrimidine, pyrrolo-pyrimidine, pyrrolo-pyridine, pyridine, purine and triazine compounds which are able to modulate epidermal growth factor receptor (EGFR), including Her-kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.
• US9908884B2
  申请人：——

  公开号：US9908884B2

  公开（公告）日：2018-03-06
• Discovery of selective irreversible inhibitors for EGFR-T790M
  作者：Wenjun Zhou、Dalia Ercan、Pasi A. Jänne、Nathanael S. Gray

  DOI：10.1016/j.bmcl.2010.12.036

  日期：2011.1

  Targeting the epidermal growth factor receptor kinase (EGFR) with ATP-competitive kinase inhibitors results in dramatic but short-lived responses in patients with EGFR mutant non small cell lung cancer. A series of novel covalent EGFR kinase inhibitors with selectivity for the clinically relevant T790M 'gatekeeper' resistance mutation relative to wild-type EGFR were discovered by library screening. A representative compound 3i was obtained through a systematic SAR study guided by mutant EGFR-dependent cellular proliferation assays. (C) 2010 Elsevier Ltd. All rights reserved.