2-甲基-2-丙基(6-氯-2-吡嗪基)氨基甲酸酯 | 652153-48-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 2-甲基-2-丙基(6-氯-2-吡嗪基)氨基甲酸酯
• 英文名称: (6-chloropyrazin-2-yl)carbamic acid tert-butyl ester
• 英文别名: Tert-butyl (6-chloropyrazin-2-YL)carbamate；tert-butyl N-(6-chloropyrazin-2-yl)carbamate
• CAS: 652153-48-5
• 化学式: C₉H₁₂ClN₃O₂
• 分子量: 229.666
• InChiKey: CFNQQJOHQAKFCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  64.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-甲基-2-丙基(6-氯-2-吡嗪基)氨基甲酸酯 在 2,6-二叔丁基-4-甲基苯酚 四(三苯基膦)钯 、 六甲基二锡 、 caesium carbonate 、 lithium chloride 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 [4-(6-{tert-Butoxycarbonyl-[3-(tert-butyl-dimethyl-silanyloxy)-propyl]-amino}-pyrazin-2-yl)-[1,3,5]triazin-2-yl]-(3-chloro-phenyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and Identification of [1,3,5]Triazine-pyridine Biheteroaryl as a Novel Series of Potent Cyclin-Dependent Kinase Inhibitors

  摘要：

  On the basis of previous studies, we identified pyrazine-pyridine A as a potent vascular endothelial growth factor inhibitor and pyrimidine-pyridine B as a moderately potent cyclin dependent kinase (CDK) inhibitor. A proposed combination of CGP-60474 and compound B led to the discovery of [1,3,5]triazine-pyridine as a new series of potent CDK inhibitors. Palladium-catalyzed C-C bond formation reactions, particularly the Negishi coupling reaction, were used to assemble various triazine-heteroaryl analogues effectively. Among them, compound 20 displayed high inhibitory potency at CDK1 IC50 = 0.021 mu M), CDK2, and CDK5 and submicromolar potency at CDK4, CDK6, and CDK7. Compound 20 also displayed high potency at GSK-3 beta. It demonstrated potent antiproliferative activity on various tumor cell lines, including HeLa, HCT-116, U937, and A375. When 20 was administered intraperitoneally at 150 and 125 mg/kg to nude mice bearing human A375 xenografts, the compound produced a significant survival increase. Molecular docking studies were conducted in an attempt to enhance the understanding of the observed structure-activity relationship.

  DOI：

  10.1021/jm040214h
• 作为产物：
  描述：

  6-氯吡嗪-2-羧酸 、 叔丁醇 在 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 3.5h， 以57%的产率得到2-甲基-2-丙基(6-氯-2-吡嗪基)氨基甲酸酯
  参考文献：
  名称：

  [EN] SUBSTITUTED TRIAZINE KINASE INHIBITORS
  [FR] INHIBITEURS DES KINASES A BASE DE TRIAZINE SUBSTITUEE

  摘要：

  本发明提供了替代的1,3,5-三嗪化合物作为激酶抑制剂，并提供了一种治疗或改善激酶介导的疾病的方法。

  公开号：

  WO2004009562A1

文献信息

• US7205298B2
  申请人：——

  公开号：US7205298B2

  公开（公告）日：2007-04-17
• Synthesis and Identification of [1,3,5]Triazine-pyridine Biheteroaryl as a Novel Series of Potent Cyclin-Dependent Kinase Inhibitors
  作者：Gee-Hong Kuo、Alan DeAngelis、Stuart Emanuel、Aihua Wang、Yan Zhang、Peter J. Connolly、Xin Chen、Robert H. Gruninger、Catherine Rugg、Angel Fuentes-Pesquera、Steven A. Middleton、Linda Jolliffe、William V. Murray

  DOI：10.1021/jm040214h

  日期：2005.7.1

  On the basis of previous studies, we identified pyrazine-pyridine A as a potent vascular endothelial growth factor inhibitor and pyrimidine-pyridine B as a moderately potent cyclin dependent kinase (CDK) inhibitor. A proposed combination of CGP-60474 and compound B led to the discovery of [1,3,5]triazine-pyridine as a new series of potent CDK inhibitors. Palladium-catalyzed C-C bond formation reactions, particularly the Negishi coupling reaction, were used to assemble various triazine-heteroaryl analogues effectively. Among them, compound 20 displayed high inhibitory potency at CDK1 IC50 = 0.021 mu M), CDK2, and CDK5 and submicromolar potency at CDK4, CDK6, and CDK7. Compound 20 also displayed high potency at GSK-3 beta. It demonstrated potent antiproliferative activity on various tumor cell lines, including HeLa, HCT-116, U937, and A375. When 20 was administered intraperitoneally at 150 and 125 mg/kg to nude mice bearing human A375 xenografts, the compound produced a significant survival increase. Molecular docking studies were conducted in an attempt to enhance the understanding of the observed structure-activity relationship.
• [EN] SUBSTITUTED TRIAZINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DES KINASES A BASE DE TRIAZINE SUBSTITUEE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2004009562A1

  公开（公告）日：2004-01-29

  The present invention provides substituted 1,3,5-triazine compounds as kinase inhibitors and a method for treating or ameliorating a kinase mediated disorder.

  本发明提供了替代的1,3,5-三嗪化合物作为激酶抑制剂，并提供了一种治疗或改善激酶介导的疾病的方法。