tert-butyl 4-(4-amino-5-cyclobutoxy-2-methylphenyl)piperidine-1-carboxylate | 1445894-90-5

• 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: tert-butyl 4-(4-amino-5-cyclobutoxy-2-methylphenyl)piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-(4-amino-5-cyclobutyloxy-2-methylphenyl)piperidine-1-carboxylate；tert-butyl 4-(4-amino-5-cyclobutyloxy-2-methylphenyl)piperidine-1-carboxylate
• CAS: 1445894-90-5
• 化学式: C₂₁H₃₂N₂O₃
• 分子量: 360.497
• InChiKey: OXCHSEGHJJKFFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  64.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,5-二氯-N-[2-[(1-甲基乙基)磺酰]苯基] 、 tert-butyl 4-(4-amino-5-cyclobutoxy-2-methylphenyl)piperidine-1-carboxylate 在 palladium diacetate 、 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 为溶剂， 生成 5-chloro-N2-(2-cyclobutoxy-5-methyl-4-(piperidin-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
• 作为产物：
  描述：

  2-氯-4-氟甲苯 在 2-双环己基膦-2',6'-二甲氧基联苯 、 platinum(IV) oxide 、 tris-(dibenzylideneacetone)dipalladium(0) 、 硫酸 、 氢气 、 caesium carbonate 、 溶剂黄146 、 potassium nitrate 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 150.0 ℃ 、101.33 kPa 条件下， 反应 0.5h， 生成 tert-butyl 4-(4-amino-5-cyclobutoxy-2-methylphenyl)piperidine-1-carboxylate
  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

• ALK KINASE INHIBITOR, AND PREPARATION METHOD AND USE THEREOF
  申请人：Beijing Pearl Biotechnology Limited Liability Company

  公开号：EP3150592A1

  公开（公告）日：2017-04-05

  An ALK kinase inhibitor compound as represented by Formula I, pharmaceutical composition containing the compound, and preparation method and use thereof in the preparation of drugs serving as an ALK inhibitor for treating cancer.

  一种由式 I 表示的 ALK 激酶抑制剂化合物、含有该化合物的药物组合物及其制备方法和在制备治疗癌症的 ALK 抑制剂药物中的用途。
• ALK kinase inhibitor, and preparation method and uses thereof
  申请人：BEIJING PEARL BIOTECHNOLOGY LIMITED LIABILITY COMPANY

  公开号：US10023593B2

  公开（公告）日：2018-07-17

  An ALK kinase inhibitor compound as represented by Formula I, pharmaceutical composition containing the compound, and preparation method and use thereof in the preparation of drugs serving as an ALK inhibitor for treating cancer.

  一种由式 I 表示的 ALK 激酶抑制剂化合物、含有该化合物的药物组合物及其制备方法和在制备治疗癌症的 ALK 抑制剂药物中的用途。
• [EN] ALK KINASE INHIBITOR, AND PREPARATION METHOD AND USE THEREOF<br/>[FR] INHIBITEUR DE LA KINASE ALK, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION<br/>[ZH] ALK激酶抑制剂及其制备方法和应用
  申请人：BEIJING PEARL BIOTECHNOLOGY LTD LIABILITY COMPANY

  公开号：WO2015180685A1

  公开（公告）日：2015-12-03

  一种如式I所示的ALK激酶抑制剂化合物，以及含有这些化合物的药物组合物，它们的制备方法和在制备用于作为ALK抑制剂的治疗癌症的药物的应用。
• ALK KINASE INHIBITOR, AND PREPARATION METHOD AND USES THEREOF
  申请人：BEIJING PEARL BIOTECHNOLOGY LIMITED LIABILITY COMPANY

  公开号：US20170247392A1

  公开（公告）日：2017-08-31

  An ALK kinase inhibitor compound as represented by Formula I, pharmaceutical composition containing the compound, and preparation method and use thereof in the preparation of drugs serving as an ALK inhibitor for treating cancer.
• 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.