N-{5-cyano-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl}-4-(3-dimethylaminoazetidin-1-yl)-6-methoxybenzene-1,3-diamine | 1421372-87-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 英文名称: N-{5-cyano-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl}-4-(3-dimethylaminoazetidin-1-yl)-6-methoxybenzene-1,3-diamine
• 英文别名: 2-{[5-Amino-4-(3-dimethylaminoazetidin-1-yl)-2-methoxyphenyl]amino}-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidine-5-carbonitrile；2-[5-amino-4-[3-(dimethylamino)azetidin-1-yl]-2-methoxyanilino]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidine-5-carbonitrile
• CAS: 1421372-87-3
• 化学式: C₂₄H₂₅N₉O
• 分子量: 455.522
• InChiKey: RVQQNNDAFDWMRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  trans 2,4-pentadienoyl chloride 、 N-{5-cyano-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl}-4-(3-dimethylaminoazetidin-1-yl)-6-methoxybenzene-1,3-diamine 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以51%的产率得到N-{5-{[5-cyano-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl]amino}-2-[3-dimethylaminoazetidin-1-yl]-4-methoxyphenyl}-trans-2,4-pentadienamide
  参考文献：
  名称：

  N-[5-(嘧啶-2-氨基)-2,4-二取代苯基]-反 式-2,4-戊二烯酰胺

  摘要：

  本发明提供了一种N‑[5‑(嘧啶‑2‑氨基)‑2,4‑二取代苯基]‑反式‑2,4‑戊二烯酰胺，如式(I)所示化合物、其药学上可接受的盐或其前药。与现有技术相比，本发明提供的化合物可抑制突变体EGFRL858R、EGFRT790M及外显子‑19缺失激活突变体的活性，因此可将式(I)所示化合物、其药学上可接受的盐或其前药作为EGFR调谐子用于治疗或预防癌症，由于这些化合物脂肪链长脂溶性高，从而提高了生物利用度，增加了血药浓度，扩大了给药时间间隔，最终减小了医疗剂量，降低了其毒副作用。

  公开号：

  CN108191861B
• 作为产物：
  描述：

  3-(2,5-dichloropyrimidin-4-yl)pyrazolo[1,5-a]pyridine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 铁粉 、 氯化铵 、 对甲苯磺酸 、 N,N-二异丙基乙胺 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 乙醇 、 N,N-二甲基乙酰胺 、 水 为溶剂， 反应 23.5h， 生成 N-{5-cyano-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl}-4-(3-dimethylaminoazetidin-1-yl)-6-methoxybenzene-1,3-diamine
  参考文献：
  名称：

  [EN] 2 - (2, 4, 5 - SUBSTITUTED -ANILINO) PYRIMIDINE DERIVATIVES AS EGFR MODULATORS USEFUL FOR TREATING CANCER
  [FR] DÉRIVÉS DE 2-(ANILINO 2,4,5-SUBSTITUÉ)PYRIMIDINE UTILISÉS COMME MODULATEURS DE L'EGFR UTILES POUR LE TRAITEMENT D'UN CANCER

  摘要：

  本发明涉及某些2-(2,4,5-取代苯胺基)嘧啶化合物及其药学上可接受的盐，这些化合物可能在治疗或预防通过某些突变形式的表皮生长因子受体介导的疾病或医疗状况中有用（例如L858R激活突变体、Exonl9缺失激活突变体和T790M耐药突变体）。这些化合物及其盐可能在治疗或预防多种不同癌症方面有用。该发明还涉及包含所述化合物和盐的药物组合物，特别是这些化合物和盐的有用多形式，用于制造所述化合物的中间体，以及使用所述化合物和盐治疗通过各种不同形式的EGFR介导的疾病的方法。

  公开号：

  WO2013014448A1

文献信息

• 2-(2,4,5-SUBSTITUTED-ANILINO) PYRIMIDINE COMPOUNDS
  申请人：BUTTERWORTH Sam

  公开号：US20130053409A1

  公开（公告）日：2013-02-28

  The present invention relates to certain 2-(2,4,5-substituted-anilino)pyrimidine compounds and pharmaceutically acceptable salts thereof which may be useful in the treatment or prevention of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (for example the L858R activating mutant, the Exon19 deletion activating mutant and the T790M resistance mutant). Such compounds and salts thereof may be useful in the treatment or prevention of a number of different cancers. The invention also relates to pharmaceutical compositions comprising said compounds and salts thereof, especially useful polymorphic forms of these compounds and salts, intermediates useful in the manufacture of said compounds and to methods of treatment of diseases mediated by various different forms of EGFR using said compounds and salts thereof.

  本发明涉及某些2-(2,4,5-取代苯胺基)嘧啶化合物及其药学上可接受的盐，这些化合物可能对通过某些突变表皮生长因子受体介导的疾病或医疗状况（例如L858R激活突变体、Exon19缺失激活突变体和T790M耐药突变体）的治疗或预防有用。这些化合物及其盐可能对多种不同的癌症的治疗或预防有用。本发明还涉及包含这些化合物及其盐的药物组合物，特别是这些化合物及其盐的有用多形式，以及用于制造这些化合物的中间体和使用这些化合物及其盐治疗通过不同形式的EGFR介导的疾病的方法。
• 2-(2,4,5-substituted-anilino) pyrimidine compounds
  申请人：Butterworth Sam

  公开号：US08946235B2

  公开（公告）日：2015-02-03

  The present invention relates to certain 2-(2,4,5-substituted-anilino)pyrimidine compounds and pharmaceutically acceptable salts thereof which may be useful in the treatment or prevention of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (for example the L858R activating mutant, the Exon19 deletion activating mutant and the T790M resistance mutant). Such compounds and salts thereof may be useful in the treatment or prevention of a number of different cancers. The invention also relates to pharmaceutical compositions comprising said compounds and salts thereof, especially useful polymorphic forms of these compounds and salts, intermediates useful in the manufacture of said compounds and to methods of treatment of diseases mediated by various different forms of EGFR using such compounds and salts thereof.

  本发明涉及某些2-(2,4,5-取代苯胺基)嘧啶化合物及其药学上可接受的盐，可用于治疗或预防经由某些突变表皮生长因子受体介导的疾病或医疗状况（例如L858R激活突变体、Exon19缺失激活突变体和T790M耐药突变体）。这些化合物及其盐可用于治疗或预防多种不同的癌症。本发明还涉及包含所述化合物及其盐的药物组合物，特别是这些化合物及其盐的有用多晶形式、制造这些化合物的中间体以及使用这些化合物及其盐治疗不同形式的EGFR介导疾病的方法。
• 2-(2,4,5-SUBSTITUTED-ANILINO)PYRIMIDINE COMPOUNDS
  申请人：AstraZeneca AB

  公开号：US20150119379A1

  公开（公告）日：2015-04-30

  The present invention relates to certain 2-(2,4,5-substituted-anilino)pyrimidine compounds and pharmaceutically acceptable salts thereof which may be useful in the treatment or prevention of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (for example the L858R activating mutant, the Exon19 deletion activating mutant and the T790M resistance mutant). Such compounds and salts thereof may be useful in the treatment or prevention of a number of different cancers. The invention also relates to pharmaceutical compositions comprising said compounds and salts thereof, especially useful polymorphic forms of these compounds and salts, intermediates useful in the manufacture of said compounds and to methods of treatment of diseases mediated by various different forms of EGFR using said compounds and salts thereof.

  本发明涉及某些2-(2,4,5-取代苯胺基)嘧啶化合物及其药学上可接受的盐，可用于治疗或预防通过某些突变的表皮生长因子受体介导的疾病或医疗情况（例如L858R激活突变体、Exon19缺失激活突变体和T790M耐药突变体）。这些化合物及其盐可用于治疗或预防多种不同类型的癌症。本发明还涉及包含所述化合物和盐的制药组合物，特别是这些化合物和盐的有用多晶形式，以及用于制造所述化合物的中间体和使用所述化合物和盐治疗不同形式EGFR介导的疾病的方法。
• 2-(2,4,5-SUBSTITUTED-ANILINO)PYRIMIDINE DERIVATIVES AS EGFR MODULATORS USEFUL FOR TREATING CANCER
  申请人：Astrazeneca AB

  公开号：EP3009431A1

  公开（公告）日：2016-04-20

  The present invention relates to certain 2-(2,4,5-substituted-anilino)pyrimidine compounds and pharmaceutically acceptable salts thereof which may be useful in the treatment or prevention of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (for example the L858R activating mutant, the Exonl9 deletion activating mutant and the T790M resistance mutant). Such compounds and salts thereof may be useful in the treatment or prevention of a number of different cancers. The invention also relates to pharmaceutical compositions comprising said compounds and salts thereof, especially useful polymorphic forms of these compounds and salts, intermediates useful in the manufacture of said compounds and to methods of treatment of diseases mediated by various different forms of EGFR using said compounds and salts thereof.

  本发明涉及某些2-(2,4,5-取代-苯胺基)嘧啶化合物及其药学上可接受的盐类，它们可用于治疗或预防通过某些突变形式的表皮生长因子受体（例如L858R激活突变体、Exonl9缺失激活突变体和T790M抗性突变体）介导的疾病或医疗状况。此类化合物及其盐类可用于治疗或预防多种不同的癌症。本发明还涉及包含上述化合物及其盐类的药物组合物、特别有用的这些化合物及其盐类的多态形式、用于制造上述化合物的中间体，以及使用上述化合物及其盐类治疗由各种不同形式的表皮生长因子受体介导的疾病的方法。
• 2-(2,4,5-substituted-anilino)pyrimidine compounds
  申请人：AstraZeneca AB

  公开号：US10017493B2

  公开（公告）日：2018-07-10

  The present invention relates to certain 2-(2,4,5-substituted-anilino)pyrimidine compounds and pharmaceutically acceptable salts thereof which may be useful in the treatment or prevention of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (for example the L858R activating mutant, the Exon19 deletion activating mutant and the T790M resistance mutant). Such compounds and salts thereof may be useful in the treatment or prevention of a number of different cancers. The invention also relates to pharmaceutical compositions comprising said compounds and salts thereof, especially useful polymorphic forms of these compounds and salts, intermediates useful in the manufacture of said compounds and to methods of treatment of diseases mediated by various different forms of EGFR using said compounds and salts thereof.

  本发明涉及某些2-(2,4,5-取代-苯胺基)嘧啶化合物及其药学上可接受的盐类，它们可用于治疗或预防通过某些突变形式的表皮生长因子受体（例如L858R激活突变体、Exon19缺失激活突变体和T790M抗性突变体）介导的疾病或医疗状况。此类化合物及其盐类可用于治疗或预防多种不同的癌症。本发明还涉及包含上述化合物及其盐类的药物组合物、特别有用的这些化合物及其盐类的多态形式、用于制造上述化合物的中间体，以及使用上述化合物及其盐类治疗由各种不同形式的表皮生长因子受体介导的疾病的方法。