4-bromo-5-chloro-N-(2-isopropoxy-5-methyl-4-(1-methylpiperidin-4-yl)phenyl)pyridin-2-amine | 1445894-99-4

• 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: 4-bromo-5-chloro-N-(2-isopropoxy-5-methyl-4-(1-methylpiperidin-4-yl)phenyl)pyridin-2-amine
• 英文别名: 4-bromo-5-chloro-N-[5-methyl-4-(1-methylpiperidin-4-yl)-2-propan-2-yloxyphenyl]pyridin-2-amine
• CAS: 1445894-99-4
• 化学式: C₂₁H₂₇BrClN₃O
• 分子量: 452.822
• InChiKey: DOJLLLSQWJAXEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  37.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-bromo-5-chloro-N-(2-isopropoxy-5-methyl-4-(1-methylpiperidin-4-yl)phenyl)pyridin-2-amine 、 2-(异丙基磺酰基)苯胺 在 tris-(dibenzylideneacetone)dipalladium(0) 、 ((2,4,6-三异丙基)苯基)二-环己基膦 、 sodium t-butanolate 作用下， 以 四氢呋喃 为溶剂， 以11%的产率得到5-chloro-N2-(2-isopropoxy-5-methyl-4-(1-methylpiperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyridine-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
• 作为产物：
  描述：

  4-(5-异丙氧基-2-甲基-4-硝基-苯基)-吡啶 在 sodium tetrahydroborate 、 palladium diacetate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 150.0 ℃ 、344.75 kPa 条件下， 反应 65.17h， 生成 4-bromo-5-chloro-N-(2-isopropoxy-5-methyl-4-(1-methylpiperidin-4-yl)phenyl)pyridin-2-amine
  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