2-chloro-4-isopropoxy-5-nitropyrimidine | 1445894-94-9

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 2-chloro-4-isopropoxy-5-nitropyrimidine
• 英文别名: 2-Chloro-4-isopropoxy-5-nitropyrimidine；2-chloro-5-nitro-4-propan-2-yloxypyrimidine
• CAS: 1445894-94-9
• 化学式: C₇H₈ClN₃O₃
• 分子量: 217.612
• InChiKey: OYNYBMBZNDNLHY-UHFFFAOYSA-N

物化性质

• 沸点：
  386.5±22.0 °C(Predicted)
• 密度：
  1.385±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  80.8
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H320,H335

反应信息

• 作为产物：
  描述：

  异丙醇 、 2,4-二氯-5 硝基嘧啶 在 potassium carbonate 作用下， 反应 16.0h， 以53%的产率得到2-chloro-4-isopropoxy-5-nitropyrimidine
  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

• 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.