5-chloro-N2-(2-isopropoxy-5-methyl-4-(1-ethylpiperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine | 1445895-03-3

• 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: 5-chloro-N2-(2-isopropoxy-5-methyl-4-(1-ethylpiperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine
• 英文别名: 5-chloro-2-N-[4-(1-ethylpiperidin-4-yl)-5-methyl-2-propan-2-yloxyphenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine
• CAS: 1445895-03-3
• 化学式: C₃₀H₄₀ClN₅O₃S
• 分子量: 586.198
• InChiKey: AZXPDNLEMGQMQS-UHFFFAOYSA-N

物化性质

• 沸点：
  720.478±70.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.225±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  8

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 、 N,N-二异丙基乙胺 、 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 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.08h， 生成 5-chloro-N2-(2-isopropoxy-5-methyl-4-(1-ethylpiperidin-4-yl)phenyl)-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

• [EN] FATTY ACID ANTICANCER DERIVATIVES AND THEIR USES<br/>[FR] DÉRIVÉS D'ACIDES GRAS ANTI-CANCÉREUX ET LEURS UTILISATIONS
  申请人：CATABASIS PHARMACEUTICALS INC

  公开号：WO2014204856A1

  公开（公告）日：2014-12-24

  The invention relates to fatty acid anticancer derivatives; compositions comprising an effective amount of a fatty acid anticancer derivative; and methods for treating or preventing cancer comprising the administration of an effective amount of a fatty acid anticancer derivative.

  这项发明涉及脂肪酸抗癌衍生物；包含有效量脂肪酸抗癌衍生物的组合物；以及治疗或预防癌症的方法，包括给予有效量脂肪酸抗癌衍生物的管理。
• 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.