3-{[4-(四甲基-1,3,2-二氧杂硼硼烷基-2-基)-1H-吡唑-1-基]甲基}氮杂环丁烷-1-羧酸叔丁酯 | 877399-31-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 中文名称: 3-{[4-(四甲基-1,3,2-二氧杂硼硼烷基-2-基)-1H-吡唑-1-基]甲基}氮杂环丁烷-1-羧酸叔丁酯
• 英文名称: tert-butyl 3-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)methyl)azetidine-1-carboxylate
• 英文别名: tert-butyl 3-{[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]methyl}azetidine-1-carboxylate；tert-butyl 3-[[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]methyl]azetidine-1-carboxylate
• CAS: 877399-31-0
• 化学式: C₁₈H₃₀BN₃O₄
• 分子量: 363.265
• InChiKey: DOHIZYSNAUZWCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.05
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  65.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-{[4-(四甲基-1,3,2-二氧杂硼硼烷基-2-基)-1H-吡唑-1-基]甲基}氮杂环丁烷-1-羧酸叔丁酯 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 6-{7-fluoroimidazo[1,2-a]pyridin-3-yl}-N-{[4-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]methyl}pyrimidin-4-amine 、 sodium carbonate 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-[(4-{1-[(azetidin-3-yl)methyl]-1H-pyrazol-4-yl}phenyl)methyl]-6-{7-methoxyimidazo[1,2-a]pyridin-3-yl}pyrimidin-4-amine trifluoroacetate
  参考文献：
  名称：

  WO2021013864A5

  摘要：

  公开号：

  WO2021013864A5
• 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 、 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex 、 potassium acetate 、 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 生成 3-{[4-(四甲基-1,3,2-二氧杂硼硼烷基-2-基)-1H-吡唑-1-基]甲基}氮杂环丁烷-1-羧酸叔丁酯
  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。
• [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
• [EN] BIFUNCTIONAL COMPOUNDS THAT DEGRADE ALK AND USES THEREOF<br/>[FR] COMPOSÉS BIFONCTIONNELS DÉGRADANT ALK ET LEURS UTILISATIONS
  申请人：[en]DANA-FARBER CANCER INSTITUTE, INC.

  公开号：WO2023278325A1

  公开（公告）日：2023-01-05

  Disclosed are bifunctional compounds (degraders) that target ALK for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the bifunctional compounds to treat diseases and disorders characterized or mediated by aberrant ALK activity.
• WO2021013864A5
  申请人：——

  公开号：WO2021013864A5

  公开（公告）日：2023-07-31
• 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)
  作者：J. Jean Cui、Michelle Tran-Dubé、Hong Shen、Mitchell Nambu、Pei-Pei Kung、Mason Pairish、Lei Jia、Jerry Meng、Lee Funk、Iriny Botrous、Michele McTigue、Neil Grodsky、Kevin Ryan、Ellen Padrique、Gordon Alton、Sergei Timofeevski、Shinji Yamazaki、Qiuhua Li、Helen Zou、James Christensen、Barbara Mroczkowski、Steve Bender、Robert S. Kania、Martin P. Edwards

  DOI：10.1021/jm2007613

  日期：2011.9.22

  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.