5-chloro-N2-(4-isopropoxy-2-(piperidin-4-yl)pyrimidin-5-yl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine | 1032903-43-7

• 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: 5-chloro-N2-(4-isopropoxy-2-(piperidin-4-yl)pyrimidin-5-yl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine
• 英文别名: 5-chloro-2-N-(2-piperidin-4-yl-4-propan-2-yloxypyrimidin-5-yl)-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine
• CAS: 1032903-43-7
• 化学式: C₂₅H₃₂ClN₇O₃S
• 分子量: 546.093
• InChiKey: UAVBPSVJXCTZOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-(异丙基磺酰基)苯胺 在 palladium diacetate 、 sodium hydride 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-chloro-N2-(4-isopropoxy-2-(piperidin-4-yl)pyrimidin-5-yl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Synthesis, Structure–Activity Relationships, and in Vivo Efficacy of the Novel Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor 5-Chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) Currently in Phase 1 and Phase 2 Clinical Trials

  摘要：

  The synthesis, preclinical profile, and in vivo efficacy in rat xenograft models of the novel and selective anaplastic lymphoma kinase inhibitor 15b (LDK378) are described. In this initial report, preliminary structure-activity relationships (SARs) are described as well as the rational design strategy employed to overcome the development deficiencies of the first generation ALK inhibitor 4 (TAE684). Compound 15b is currently in phase 1 and phase 2 clinical trials with substantial antitumor activity being observed in ALK-positive cancer patients.

  DOI：

  10.1021/jm400402q

文献信息

• COMPOUNDS AND COMPOSITIONS AS PROTEIN KINASE INHIBITORS
  申请人：Michellys Pierre-Yves

  公开号：US20080176881A1

  公开（公告）日：2008-07-24

  The invention provides novel pyrimidine and pyridine derivatives and pharmaceutical compositions thereof, and methods for using such compounds. For example, the pyrimidine and pyridine derivatives of the invention may be used to treat, ameliorate or prevent a condition which responds to inhibition of anaplastic lymphoma kinase (ALK) activity, focal adhesion kinase (FAK), zeta-chain-associated protein kinase 70 (ZAP-70), insulin-like growth factor (IGF-1R), or a combination thereof.

  本发明提供了新型嘧啶和吡啶衍生物及其药物组合物，以及使用这些化合物的方法。例如，本发明的嘧啶和吡啶衍生物可用于治疗、改善或预防对抗无形淋巴瘤激酶（ALK）活性、焦点粘附激酶（FAK）、ζ链相关蛋白激酶70（ZAP-70）、胰岛素样生长因子（IGF-1R）或其组合的疾病。
• Compounds and compositions as protein kinase inhibitors
  申请人：IRM LLC

  公开号：EP2537830A1

  公开（公告）日：2012-12-26

  The invention provides novel pyrimidine derivatives of formula (1) and pharmaceutical compositions thereof, and methods for using such compounds. For example, the pyrimidine derivatives of the invention may be used to treat, ameliorate or prevent a condition which responds to inhibition of anaplastic lymphoma kinase (ALK) activity, focal adhesion kinase (FAK), zeta-chain-associated protein kinase 70 (ZAP-70), insulin-like growth factor (IGF-1R), or a combination thereof.

  本发明提供了式(1)的新型嘧啶衍生物及其药物组合物，以及使用此类化合物的方法。例如，本发明的嘧啶衍生物可用于治疗、改善或预防对抑制无性淋巴瘤激酶（ALK）活性、病灶粘附激酶（FAK）、zeta-链相关蛋白激酶 70（ZAP-70）、胰岛素样生长因子（IGF-1R）或其组合有反应的病症。
• COMPOUNDS AND COMPOSITION AS PROTEIN KINASE INHIBITORS
  申请人：Novartis AG

  公开号：EP3012249A1

  公开（公告）日：2016-04-27

  The invention provides novel pyrimidine and pyridine derivatives of formula (1) and pharmaceutical compositions thereof, and methods for using such compounds. For example, the pyrimidine and pyridine derivatives of the invention may be used to treat, ameliorate or prevent a condition which responds to inhibition of anaplastic lymphoma kinase (ALK) activity, focal adhesion kinase (FAK), zeta-chain-associated protein kinase 70 (ZAP-70), insulin-like growth factor (IGF-1R), or a combination thereof.

  本发明提供了式(1)的新型嘧啶和吡啶衍生物及其药物组合物，以及使用此类化合物的方法。例如，本发明的嘧啶和吡啶衍生物可用于治疗、改善或预防对抑制无性淋巴瘤激酶（ALK）活性、病灶粘附激酶（FAK）、zeta-链相关蛋白激酶 70（ZAP-70）、胰岛素样生长因子（IGF-1R）或其组合有反应的病症。
• Compounds and composition as protein kinase inhibitors
  申请人：Novartis AG

  公开号：EP2311807B1

  公开（公告）日：2015-11-11
• US8039479B2
  申请人：——

  公开号：US8039479B2

  公开（公告）日：2011-10-18