3-(5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-ylamino)phenol | 1130155-68-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 3-(5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-ylamino)phenol
• 英文别名: 3-(8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6-tetraen-3-ylamino)phenol
• CAS: 1130155-68-8
• 化学式: C₁₅H₁₄N₄OS
• 分子量: 298.368
• InChiKey: QBYGQMGKNAVQCS-UHFFFAOYSA-N

物化性质

• 沸点：
  559.4±45.0 °C(predicted)
• 密度：
  1.442±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  98.3
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,4-bis(benzyloxy)-5-isopropylbenzoic acid 、 3-(5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-ylamino)phenol 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成
  参考文献：
  名称：

  Design, synthesis and molecular mechanisms of novel dual inhibitors of heat shock protein 90/phosphoinositide 3-kinase alpha (Hsp90/PI3Kα) against cutaneous melanoma

  摘要：

  Overexpression of heat shock protein 90 (Hsp90) is common in various types of cancer. In cutaneous melanoma, a cancer with one of the high levels of Hsp90 overexpression, such expression was correlated with a panel of protein kinases, thus offering an opportunity to identify Hsp90-based multi-kinase inhibitors for novel cancer therapies. Towards this goal, we utilized a 2,4-dihydroxy-5-isopropylbenzate-based Hsp90 inhibitor scaffold and thieno[2,3-d]pyrimidine-based kinase inhibitor scaffold to develop a Hsp90-inhibiting compound library. Our inhibitory compound named 8m inhibited Hsp90 and PI3K alpha with an IC50 value of 38.6 nM and 48.4 nM, respectively; it displayed improved cellular activity which could effectively induce cell cycle arrest and apoptosis in melanoma cells and lead to the inhibition of cell proliferation, colony formation, migration and invasion. Our results demonstrated 8m to be a promising lead compound for further therapeutic potential assessment of Hsp90/PI3K alpha dual inhibitors in melanoma targeted therapy.

  DOI：

  10.1080/14756366.2019.1596903
• 作为产物：
  描述：

  4-氯-5,6-二氢吡啶并[4',3'4,5]噻吩并[2,3-D]嘧啶-7(8H)-甲酸叔丁基酯 、 3-氨基苯酚 在 盐酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 异丙醇 、 水 为溶剂， 反应 23.0h， 生成 3-(5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-ylamino)phenol
  参考文献：
  名称：

  [EN] SUBSTITUTED TRICYCLIC COMPOUNDS AND METHODS OF USE THEREOF
  [FR] COMPOSÉS TRICYCLIQUES SUBSTITUÉS ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  这项发明涉及新颖化合物及其制备方法，治疗疾病的方法，特别是癌症，包括给予这些化合物，以及制备用于治疗或预防疾病，特别是癌症的药物组合物的方法。

  公开号：

  WO2009033581A1

文献信息

• Substituted tricyclic compounds and methods of use thereof
  申请人：Schirok Hartmut

  公开号：US08524722B2

  公开（公告）日：2013-09-03

  This invention relates to novel compounds and processes for their preparation, methods of treating diseases, particularly cancer, comprising administering said compounds, and methods of making pharmaceutical compositions for the treatment or prevention of disorders, particularly cancer.

  本发明涉及新型化合物及其制备方法，涉及用于治疗疾病的方法，尤其是癌症，包括给予该化合物的方法，以及制备用于治疗或预防疾病，尤其是癌症的药物组合物的方法。
• SUBSTITUTED TRICYCLIC COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Schirok Hartmut

  公开号：US20110021493A1

  公开（公告）日：2011-01-27

  This invention relates to novel compounds and processes for their preparation, methods of treating diseases, particularly cancer, comprising administering said compounds, and methods of making pharmaceutical compositions for the treatment or prevention of disorders, particularly cancer.

  本发明涉及新型化合物及其制备方法，涉及使用该化合物治疗疾病的方法，特别是癌症，以及制备用于治疗或预防疾病，特别是癌症的药物组合物的方法。
• US8524722B2
  申请人：——

  公开号：US8524722B2

  公开（公告）日：2013-09-03
• [EN] SUBSTITUTED TRICYCLIC COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS TRICYCLIQUES SUBSTITUÉS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：BAYER HEALTHCARE AG

  公开号：WO2009033581A1

  公开（公告）日：2009-03-19

  This invention relates to novel compounds and processes for their preparation, methods of treating diseases, particularly cancer, comprising administering said compounds, and methods of making pharmaceutical compositions for the treatment or prevention of disorders, particularly cancer.

  这项发明涉及新颖化合物及其制备方法，治疗疾病的方法，特别是癌症，包括给予这些化合物，以及制备用于治疗或预防疾病，特别是癌症的药物组合物的方法。
• Design, synthesis and molecular mechanisms of novel dual inhibitors of heat shock protein 90/phosphoinositide 3-kinase alpha (Hsp90/PI3Kα) against cutaneous melanoma
  作者：Feifei Qin、Yali Wang、Xian Jiang、Yujia Wang、Nan Zhang、Xiang Wen、Lian Wang、Qinglin Jiang、Gu He

  DOI：10.1080/14756366.2019.1596903

  日期：2019.1.1

  Overexpression of heat shock protein 90 (Hsp90) is common in various types of cancer. In cutaneous melanoma, a cancer with one of the high levels of Hsp90 overexpression, such expression was correlated with a panel of protein kinases, thus offering an opportunity to identify Hsp90-based multi-kinase inhibitors for novel cancer therapies. Towards this goal, we utilized a 2,4-dihydroxy-5-isopropylbenzate-based Hsp90 inhibitor scaffold and thieno[2,3-d]pyrimidine-based kinase inhibitor scaffold to develop a Hsp90-inhibiting compound library. Our inhibitory compound named 8m inhibited Hsp90 and PI3K alpha with an IC50 value of 38.6 nM and 48.4 nM, respectively; it displayed improved cellular activity which could effectively induce cell cycle arrest and apoptosis in melanoma cells and lead to the inhibition of cell proliferation, colony formation, migration and invasion. Our results demonstrated 8m to be a promising lead compound for further therapeutic potential assessment of Hsp90/PI3K alpha dual inhibitors in melanoma targeted therapy.