4-Methoxy-1-[2-(methylthio)-4-pyrimidinyl]-1H-indazole | 1424351-15-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 4-Methoxy-1-[2-(methylthio)-4-pyrimidinyl]-1H-indazole
• 英文别名: 4-methoxy-1-(2-methylsulfanylpyrimidin-4-yl)indazole
• CAS: 1424351-15-4
• 化学式: C₁₃H₁₂N₄OS
• 分子量: 272.33
• InChiKey: NCWNCGWMLYJNTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  78.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-Methoxy-1-[2-(methylthio)-4-pyrimidinyl]-1H-indazole 在 三溴化硼 作用下， 以92%的产率得到1-(2-(methylthio)pyrimidin-4-yl)-1H-indazol-4-ol
  参考文献：
  名称：

  Development of amino-pyrimidine inhibitors of c-Jun N-terminal kinase (JNK): Kinase profiling guided optimization of a 1,2,3-benzotriazole lead

  摘要：

  A series of amino-pyrimidines was developed based upon an initial kinase cross-screening hit from a CDK2 program. Kinase profiling and structure-based drug design guided the optimization from the initial 1,2,3-benzotriazole hit to a potent and selective JNK inhibitor, compound 24f (JNK1 and 2 IC50 = 16 and 66 nM, respectively), with bioavailability in rats and suitable for further in vivo pharmacological evaluation. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.047
• 作为产物：
  描述：

  2-甲硫基-4-氯嘧啶 在 potassium carbonate 、 sodium hydroxide 、 肼 作用下， 以 乙醇 为溶剂， 生成 4-Methoxy-1-[2-(methylthio)-4-pyrimidinyl]-1H-indazole
  参考文献：
  名称：

  Development of amino-pyrimidine inhibitors of c-Jun N-terminal kinase (JNK): Kinase profiling guided optimization of a 1,2,3-benzotriazole lead

  摘要：

  A series of amino-pyrimidines was developed based upon an initial kinase cross-screening hit from a CDK2 program. Kinase profiling and structure-based drug design guided the optimization from the initial 1,2,3-benzotriazole hit to a potent and selective JNK inhibitor, compound 24f (JNK1 and 2 IC50 = 16 and 66 nM, respectively), with bioavailability in rats and suitable for further in vivo pharmacological evaluation. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.047

文献信息

• [EN] EGFR INHIBITOR, AND PREPARATION AND APPLICATION THEREOF<br/>[FR] INHIBITEUR D'EGFR, ET PRÉPARATION ET APPLICATION ASSOCIÉES<br/>[ZH] EGFR抑制剂及其制备和应用
  申请人：SHANGHAI HANSOH BIOMEDICAL CO LTD

  公开号：WO2016054987A1

  公开（公告）日：2016-04-14

  一种如式(I)所示的4-取代-2-(N-(5-取代烯丙酰胺基)苯基)氨基)嘧啶衍生物以及其作为EGFR抑制剂的制备和应用，该化合物具有抑制L858R EGFR突变体、T790M EGFR突变体和外显子19缺失激活突变体的活性，可以用来治疗单独或部分地由EGFR突变体活性介导疾病，在预防与治疗癌症尤其是非小细胞肺癌药物中的具有广泛应用。
• EGFR inhibitor, preparation method and use thereof
  申请人：Shanghai Hansoh Biomedical Co., Ltd.

  公开号：US10259820B2

  公开（公告）日：2019-04-16

  Epidermal growth factor receptor (EGFR) inhibitors are provided. In particular, 4-substituted-2-(N-(5-substituted allyl amide)phenyl)amino)pyrimidine derivatives of formula (I), a preparation method and use thereof as an EGFR inhibitor are provided. The 4-substituted-2-(N-(5-substituted allyl amide)phenyl)amino)pyrimidine derivatives of formula (I) have inhibitory activity against the L858R EGFR mutant, the T790M EGFR mutant and the exon 19 deletion activating mutant, and can be used to treat diseases mediated alone or in part by EGFR mutant activity. The derivatives of formula (I) can be used to treat and/or prevent cancers, particularly non-small cell lung cancer.

  提供了表皮生长因子受体（EGFR）抑制剂。特别是提供了式(I)的4-取代-2-(N-(5-取代烯丙基酰胺)苯基)氨基)嘧啶衍生物、其制备方法及其作为表皮生长因子受体抑制剂的用途。式（I）的 4-取代-2-(N-(5-取代烯丙基酰胺)苯基)氨基)嘧啶衍生物对 L858R 表皮生长因子受体突变体、T790M 表皮生长因子受体突变体和外显子 19 缺失激活突变体具有抑制活性，可用于治疗单独或部分由表皮生长因子受体突变体活性介导的疾病。式（I）的衍生物可用于治疗和/或预防癌症，尤其是非小细胞肺癌。
• EGFR INHIBITOR, AND PREPARATION AND APPLICATION THEREOF
  申请人：Shanghai Hansoh Biomedical Co., Ltd.

  公开号：EP3205650B1

  公开（公告）日：2021-08-04
• EP3205650A1
  申请人：——

  公开号：EP3205650A1

  公开（公告）日：2017-08-16
• EGFR INHIBITOR, PREPARATION METHOD AND USE THEREOF
  申请人：Shanghai Hansoh Biomedical Co., Ltd.

  公开号：US20170313714A1

  公开（公告）日：2017-11-02

  Epidermal growth factor receptor (EGFR) inhibitors are provided. In particular, 4-substituted-2-(N-(5-substituted allyl amide)phenyl)amino)pyrimidine derivatives of formula (I), a preparation method and use thereof as an EGFR inhibitor are provided. The 4-substituted-2-(N-(5-substituted allyl amide)phenyl)amino)pyrimidine derivatives of formula (I) have inhibitory activity against the L858R EGFR mutant, the T790M EGFR mutant and the exon 19 deletion activating mutant, and can be used to treat diseases mediated alone or in part by EGFR mutant activity. The derivatives of formula (I) can be used to treat and/or prevent cancers, particularly non-small cell lung cancer.