1-(4-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-1-yl)-2-(dimethylamino)ethanone | 1190399-47-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(4-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-1-yl)-2-(dimethylamino)ethanone
• 英文别名: 1-(4-(4-(5-Chloro-4-(2-(isopropylsulfonyl)phenylamino)pyrimidin-2-ylamino)-5-isopropoxy-2-methylphenyl)piperidin-1-yl)-2-(dimethylamino)ethanone；1-[4-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-2-methyl-5-propan-2-yloxyphenyl]piperidin-1-yl]-2-(dimethylamino)ethanone
• CAS: 1190399-47-3
• 化学式: C₃₂H₄₃ClN₆O₄S
• 分子量: 643.25
• InChiKey: ADAQBVKANMBBGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-(4-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-1-yl)-2-(dimethylamino)ethanone 、 sodium acetate 、 氯乙醛 、 盐酸 在 水 作用下， 以 水 为溶剂， 反应 3.0h， 生成 2,4-二羟基吡咯[2,3-d]嘧啶
  参考文献：
  名称：

  Compounds and compositions as protein kinase inhibitors

  摘要：

  本发明提供了新型嘧啶衍生物及其制药组合物，以及使用这些化合物的方法。例如，本发明的嘧啶衍生物可用于治疗、改善或预防对抗无形淋巴瘤激酶（ALK）活性、c-ros癌基因（ROS）、类胰岛素生长因子（IGF-1R）和/或胰岛素受体（InsR）或其组合的疾病。

  公开号：

  US08592432B2
• 作为产物：
  描述：

  2-(异丙基磺酰基)苯胺 在 palladium diacetate 、 sodium hydride 、 caesium carbonate 、 三乙胺 、 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， 反应 13.08h， 生成 1-(4-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-5-isopropoxy-2-methylphenyl)piperidin-1-yl)-2-(dimethylamino)ethanone
  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：Chen Bei

  公开号：US20110135668A1

  公开（公告）日：2011-06-09

  The invention provides novel pyrimidine derivatives 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, c-ros oncogene (ROS), insulin-like growth factor (IGF-1R), and/or insulin receptor (InsR) or a combination thereof.

  本发明提供了新型嘧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，本发明的嘧啶衍生物可用于治疗、改善或预防对抗肿瘤相关蛋白anaplastic lymphoma kinase（ALK）活性、c-ros癌基因（ROS）、胰岛素样生长因子（IGF-1R）和/或胰岛素受体（InsR）或其组合的疾病状态。
• US8592432B2
  申请人：——

  公开号：US8592432B2

  公开（公告）日：2013-11-26
• [EN] COMPOUNDS AND COMPOSITIONS AS PROTEIN KINASE INHIBITORS<br/>[FR] COMPOSÉS ET COMPOSITIONS COMME INHIBITEURS DE LA PROTÉINE KINASE
  申请人：IRM LLC

  公开号：WO2009126515A1

  公开（公告）日：2009-10-15

  The invention provides novel pyrimidine derivatives 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, c-ros oncogene (ROS), insulin-like growth factor (IGF-1R), and/or insulin receptor (InsR) or a combination thereof.
• Synthesis, Structure–Activity Relationships, and in Vivo Efficacy of the Novel Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor 5-Chloro-<i>N</i>2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-<i>N</i>4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) Currently in Phase 1 and Phase 2 Clinical Trials
  作者：Thomas H. Marsilje、Wei Pei、Bei Chen、Wenshuo Lu、Tetsuo Uno、Yunho Jin、Tao Jiang、Sungjoon Kim、Nanxin Li、Markus Warmuth、Yelena Sarkisova、Frank Sun、Auzon Steffy、AnneMarie C. Pferdekamper、Allen G. Li、Sean B. Joseph、Young Kim、Bo Liu、Tove Tuntland、Xiaoming Cui、Nathanael S. Gray、Ruo Steensma、Yongqin Wan、Jiqing Jiang、Greg Chopiuk、Jie Li、W. Perry Gordon、Wendy Richmond、Kevin Johnson、Jonathan Chang、Todd Groessl、You-Qun He、Andrew Phimister、Alex Aycinena、Christian C. Lee、Badry Bursulaya、Donald S. Karanewsky、H. Martin Seidel、Jennifer L. Harris、Pierre-Yves Michellys

  DOI：10.1021/jm400402q

  日期：2013.7.25

  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.
• Compounds and compositions as protein kinase inhibitors
  申请人：Chen Bei

  公开号：US08592432B2

  公开（公告）日：2013-11-26

  The invention provides novel pyrimidine derivatives 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, c-ros oncogene (ROS), insulin-like growth factor (IGF-1R), and/or insulin receptor (InsR) or a combination thereof.

  本发明提供了新型嘧啶衍生物及其制药组合物，以及使用这些化合物的方法。例如，本发明的嘧啶衍生物可用于治疗、改善或预防对抗无形淋巴瘤激酶（ALK）活性、c-ros癌基因（ROS）、类胰岛素生长因子（IGF-1R）和/或胰岛素受体（InsR）或其组合的疾病。