1,1-Dimethylethyl 3-[[4-[6-amino-5-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-3-pyridinyl]-1H-pyrazol-1-yl]methyl]-1-azetidinecarboxylate | 877399-32-1

• 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: 1,1-Dimethylethyl 3-[[4-[6-amino-5-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-3-pyridinyl]-1H-pyrazol-1-yl]methyl]-1-azetidinecarboxylate
• 英文别名: tert-butyl 3-[[4-[6-amino-5-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-3-yl]pyrazol-1-yl]methyl]azetidine-1-carboxylate
• CAS: 877399-32-1
• 化学式: C₂₅H₂₈Cl₂FN₅O₃
• 分子量: 536.433
• InChiKey: OQZGQPDIZCADIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  95.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1,1-Dimethylethyl 3-[[4-[6-amino-5-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-3-pyridinyl]-1H-pyrazol-1-yl]methyl]-1-azetidinecarboxylate 在 DOWEX 50WX₂-400 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以78%的产率得到5-(1-(azetidin-3-ylmethyl)-1H-pyrazol-4-yl)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine
  参考文献：
  名称：

  Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors

  摘要：

  提供了式1的对映纯化合物，以及它们的合成和使用方法。优选化合物是c-Met蛋白激酶的强效抑制剂，并且在治疗异常细胞生长紊乱，如癌症方面具有用处。

  公开号：

  US20060046991A1
• 作为产物：
  描述：

  3-羟甲基氮杂环丁烷-1-羧酸叔丁酯 在 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex 、 potassium acetate 、 sodium hydride 、 sodium carbonate 、 三乙胺 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 生成 1,1-Dimethylethyl 3-[[4-[6-amino-5-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-3-pyridinyl]-1H-pyrazol-1-yl]methyl]-1-azetidinecarboxylate
  参考文献：
  名称：

  Structure Based Drug Design of Crizotinib (PF-02341066), a Potent and Selective Dual Inhibitor of Mesenchymal–Epithelial Transition Factor (c-MET) Kinase and Anaplastic Lymphoma Kinase (ALK)

  摘要：

  Because of the critical roles of aberrant signaling in cancer, both c-MET and ALK receptor tyrosine kinases are attractive oncology targets for therapeutic intervention. The cocrystal structure of 3 (PHA-665752), bound to c-MET kinase domain, revealed a novel ATP site environment, which served as the target to guide parallel, multiattribute drug design. A novel 2-amino-5-aryl-3-benzyloxypyridine series was created to more effectively make the key interactions achieved with 3. In the novel series, the 2-aminopyridine core allowed a 3-benzyloxy group to reach into the same pocket as the 2,6-dichlorophenyl group of 3 via a more direct vector and thus with a better ligand efficiency (LE). Further optimization of the lead series generated the clinical candidate crizotinib (PF-02341066), which demonstrated potent in vitro and in vivo c-MET kinase and ALK inhibition, effective tumor growth inhibition, and good pharmaceutical properties.

  DOI：

  10.1021/jm2007613

文献信息

• Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors
  申请人：Cui Jean Jingrong

  公开号：US20060046991A1

  公开（公告）日：2006-03-02

  Enantiomerically pure compound of formula 1 are provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.

  提供了式1的对映纯化合物，以及它们的合成和使用方法。优选化合物是c-Met蛋白激酶的强效抑制剂，并且在治疗异常细胞生长紊乱，如癌症方面具有用处。
• Pyrazole-substituted aminoheteroaryl compounds as protein kinase inhibitors
  申请人：Cui Jean Jingrong

  公开号：US20060128724A1

  公开（公告）日：2006-06-15

  Compounds of formula 1 are provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.

  提供了化学式1的化合物，以及它们的合成和使用方法。首选的化合物是c-Met蛋白激酶的强效抑制剂，并且在治疗异常细胞生长障碍，例如癌症方面非常有用。
• ENANTIOMERICALLY PURE AMINOHETEROARYL COMPOUNDS AS PROTEIN KINASE INHIBITORS
  申请人：CUI Jingrong Jean

  公开号：US20140288086A1

  公开（公告）日：2014-09-25

  Enantiomerically pure compound of formula 1 are provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.

  本发明提供了公式1的对映纯化合物，以及它们的合成和使用方法。首选化合物是c-Met蛋白激酶的强效抑制剂，可用于治疗异常细胞增生性疾病，例如癌症。
• [EN] PYRAZOLE-SUBSTITUTED AMINOHETEROARYL COMPOUNDS AS PROTEIN KINASE INHIBITORS<br/>[FR] COMPOSES AMINOHETEROARYLE A SUBSTITUTION PYRAZOLE SERVANT D'INHIBITEURS DE PROTEINE KINASE
  申请人：PFIZER

  公开号：WO2006021881A3

  公开（公告）日：2006-05-18
• PYRAZOLE-SUBSTITUTED AMINOHETEROARYL COMPOUNDS AS PROTEIN KINASE INHIBITORS
  申请人：Pfizer Inc.

  公开号：EP1784396B8

  公开（公告）日：2011-04-20