5-chloro-N2-(2-cyclopropyloxy-4-(piperidin-4-yl)-5-methylphenyl)-N4-(3-(isopropylsulfonyl)-1-methyl-1H-pyrazol-4-yl)pyrimidine-2,4-diamine

• 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-cyclopropyloxy-4-(piperidin-4-yl)-5-methylphenyl)-N4-(3-(isopropylsulfonyl)-1-methyl-1H-pyrazol-4-yl)pyrimidine-2,4-diamine
• 英文别名: 5-chloro-N²-(2-cyclopropoxy-4-piperidin-4-yl-5-methylphenyl)-N⁴-[1-methyl-3-(isopropylsulfonyl)-1H-pyrazol-4-yl]-pyrimidin-2,4-diamine；5-chloro-2-N-(2-cyclopropyloxy-5-methyl-4-piperidin-4-ylphenyl)-4-N-(1-methyl-3-propan-2-ylsulfonylpyrazol-4-yl)pyrimidine-2,4-diamine
• 化学式: C₂₆H₃₄ClN₇O₃S
• 分子量: 560.12
• InChiKey: ZVTCEMYLHSLGPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  131
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-chloro-N2-(2-cyclopropyloxy-4-(piperidin-4-yl)-5-methylphenyl)-N4-(3-(isopropylsulfonyl)-1-methyl-1H-pyrazol-4-yl)pyrimidine-2,4-diamine 在 二异丁基氢化铝 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 2-(4-(4-(5-chloro-4-(3-(isopropyl sulfonyl)-1-methyl-1H-pyrazol-4-amino)pyrimidin-2-amino)-5-cyclopropoxy-2-methylphenyl)piperidin-1-yl)-2-methyl-1-propanol
  参考文献：
  名称：

  EP3150592

  摘要：

  公开号：
• 作为产物：
  描述：

  2-溴-4-氟-5-硝基甲苯 在 bis-triphenylphosphine-palladium(II) chloride 、 氢气 、 palladium diacetate 、 sodium carbonate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-chloro-N2-(2-cyclopropyloxy-4-(piperidin-4-yl)-5-methylphenyl)-N4-(3-(isopropylsulfonyl)-1-methyl-1H-pyrazol-4-yl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Discovery of 2-arylamino-4-(1-methyl-3-isopropylsulfonyl-4-pyrazol-amino)pyrimidines as potent anaplastic lymphoma kinase (ALK) inhibitors

  摘要：

  A new series of 2,4-diamino pyrimidine derivatives with a sulfone-substituted pyrazole right side-chain were discovered as potent anaplastic lymphoma kinase inhibitors. Structure-activity relationship of the left side-chain on phenyl substitutions were explored which delivered many potent ALK inhibitors. Among them, 29a showed favorable pharmacokinetic profiles in rats and dogs together with significant antitumor efficacy in EML4-ALK fusion xenograft model. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.06.021

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.
• Discovery of 2-arylamino-4-(1-methyl-3-isopropylsulfonyl-4-pyrazol-amino)pyrimidines as potent anaplastic lymphoma kinase (ALK) inhibitors
  作者：Peilong Zhang、Jiaqiang Dong、Boyu Zhong、Deyi Zhang、Can Jin、Xuejing Meng、Desheng Sun、Xiangyuan Xu、Yong Zhou、Zhi Liang、Minghua Ji、Hailong Li、Tao Xu、Guowei Song、Ling Zhang、Gang Chen、Hongbin Yuan、Joe Shih、Ruihao Zhang、Guojun Hou、Ying Jin、Qiong Yang

  DOI：10.1016/j.bmcl.2015.06.021

  日期：2015.9

  A new series of 2,4-diamino pyrimidine derivatives with a sulfone-substituted pyrazole right side-chain were discovered as potent anaplastic lymphoma kinase inhibitors. Structure-activity relationship of the left side-chain on phenyl substitutions were explored which delivered many potent ALK inhibitors. Among them, 29a showed favorable pharmacokinetic profiles in rats and dogs together with significant antitumor efficacy in EML4-ALK fusion xenograft model. (C) 2015 Elsevier Ltd. All rights reserved.