(3-chlorophenyl)-(4-chloro-[1,3,5]triazin-2-yl)carbamic acid tert-butyl ester | 652153-34-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3-chlorophenyl)-(4-chloro-[1,3,5]triazin-2-yl)carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-(3-chlorophenyl)-N-(4-chloro-1,3,5-triazin-2-yl)carbamate
• CAS: 652153-34-9
• 化学式: C₁₄H₁₄Cl₂N₄O₂
• 分子量: 341.197
• InChiKey: JBBOFPCHHAMUDW-UHFFFAOYSA-N

物化性质

• 沸点：
  488.1±47.0 °C(Predicted)
• 密度：
  1.380±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  68.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3-chlorophenyl)-(4-chloro-[1,3,5]triazin-2-yl)carbamic acid tert-butyl ester 在 2,6-二叔丁基-4-甲基苯酚 四(三苯基膦)钯 、 六甲基二锡 、 三氟乙酸 、 lithium chloride 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 3-((4-(4-((3-chlorophenyl)amino)-1,3,5-triazin-2-yl)-2-pyridinyl)amino)-1-propanol
  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：

  3-氯苯胺 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 73.0h， 生成 (3-chlorophenyl)-(4-chloro-[1,3,5]triazin-2-yl)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

文献信息

• [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。
• Substituted triazine kinase inhibitors
  申请人：Janssen Pharmaceutica NV

  公开号：EP2256108A1

  公开（公告）日：2010-12-01

  The present invention provides substituted 1,3,5-triazine compounds of Formula (I): wherein X, Y and Z are independently selected from the group consisting of CH and N; wherein m is an integer from 2 to 5; wherein X, Y and Z include at least one CH atom and at least one N atom; and, wherein a N atom may simultaneously occupy only the X and Z positions; R1 is selected from the group consisting of hydrogen and NH2; and, R2 is selected from the group consisting of phenyl (wherein phenyl is substituted with one substituent selected from the group consisting of halogen and heterocyclyl) and 1,4-benzodioxinyl; and pharmaceutically acceptable salts thereof as kinase inhibitors and a method for treating or ameliorating a kinase mediated disorder.

  本发明提供了式 (I) 的取代 1,3,5 三嗪化合物： 其中 X、Y 和 Z 独立地选自由 CH 和 N 组成的组；其中 m 是 2 至 5 的整数；其中 X、Y 和 Z 包括至少一个 CH 原子和至少一个 N 原子；其中一个 N 原子可以同时只占据 X 和 Z 的位置； R1 选自由氢和 NH2 组成的组；以及 R2 选自苯基（其中苯基被一个选自卤素和杂环基的取代基取代）和 1,4-苯并二噁烷基； 及其药学上可接受的盐，作为激酶抑制剂和一种治疗或改善激酶介导的疾病的方法。
• SUBSTITUTED TRIAZINE KINASE INHIBITORS
  申请人：Janssen Pharmaceutica NV

  公开号：EP1546121B1

  公开（公告）日：2012-08-29
• 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.