1-iodo-3-[3-(4-methyl-piperazin-1-yl)-cyclobutyl]-imidazo[1,5-a]pyrazin-8-ylamine | 867165-82-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并[1,5-a]吡嗪
• 英文名称: 1-iodo-3-[3-(4-methyl-piperazin-1-yl)-cyclobutyl]-imidazo[1,5-a]pyrazin-8-ylamine
• CAS: 867165-82-0
• 化学式: C₁₅H₂₁IN₆
• 分子量: 412.276
• InChiKey: GGCDOLDXNOVYLQ-PHIMTYICSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.41
• 重原子数：
  22.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  62.69
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  8-chloro-1-iodo-3-[3-(4-methyl-piperazin-1-yl)-cyclobutyl]-imidazo[1,5-a]pyrazine 在 氨 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 72.0h， 生成 1-iodo-3-[3-(4-methyl-piperazin-1-yl)-cyclobutyl]-imidazo[1,5-a]pyrazin-8-ylamine
  参考文献：
  名称：

  Combined treatment with an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors

  摘要：

  本发明提供了一种治疗患者体内NSCL、胰腺、结肠或乳腺癌肿瘤或肿瘤转移的方法，包括向患者同时或顺序给予治疗有效量的EGFR激酶抑制剂和一种使肿瘤细胞对EGFR激酶抑制剂产生敏感性的药物的组合，其中该药物是mTOR抑制剂，可以附加其他药物或治疗，如其他抗癌药物或放射治疗。本发明还提供了一种治疗患者体内肿瘤或肿瘤转移的方法，包括向患者同时或顺序给予治疗有效量的EGFR激酶抑制剂和一种使肿瘤细胞对EGFR激酶抑制剂产生敏感性的药物的组合，其中该药物是一种能够结合并直接抑制mTORC1和mTORC2激酶的mTOR抑制剂。本发明还提供了一种制药组合物，包括一种能够结合并直接抑制mTORC1和mTORC2激酶的EGFR激酶抑制剂和mTOR抑制剂，以及一种药用载体。本发明中可用于实施该方法的EGFR激酶抑制剂的首选示例是化合物厄洛替尼盐酸盐（也称为TARCEVA®）。

  公开号：

  US20070280928A1

文献信息

• Fused bicyclic mTOR inhibitors
  申请人：Chen Xin

  公开号：US20070112005A1

  公开（公告）日：2007-05-17

  Compounds represented by Formula (I) or a pharmaceutically acceptable salt thereof, are inhibitors of mTOR and useful in the treatment of cancer.

  由化学式(I)代表的化合物或其药用可接受的盐，是mTOR的抑制剂，可用于癌症的治疗。
• COMBINED TREATMENT WITH AN EGFR KINASE INHIBITOR AND AN AGENT THAT SENSITIZES TUMOR CELLS TO THE EFFECTS OF EGFR KINASE INHIBITORS
  申请人：Buck Elizabeth A.

  公开号：US20100166776A1

  公开（公告）日：2010-07-01

  The present invention provides a method for treating NSCL, pancreatic, colon or breast cancer tumors or tumor metastases in a patient, comprising administering to the patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein the agent is an mTOR inhibitor, with or without additional agents or treatments, such as other anti-cancer drugs or radiation therapy. The present invention also provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein said agent is an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases. The present invention also provides a pharmaceutical composition comprising an EGFR kinase inhibitor and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases, in a pharmaceutically acceptable carrier. A preferred example of an EGFR kinase inhibitor that can be used in practicing the methods of this invention is the compound erlotinib HCl (also known as TARCEVA®).

  本发明提供了一种用于治疗患有非小细胞肺癌、胰腺癌、结肠癌或乳腺癌肿瘤或肿瘤转移的患者的方法，包括同时或依次向患者施用治疗有效量的EGFR激酶抑制剂和一种能够使肿瘤细胞对EGFR激酶抑制剂产生敏感性的药物，其中该药物是mTOR抑制剂，可与其他抗癌药物或放射治疗等附加药物或治疗一起使用。本发明还提供了一种用于治疗患者的肿瘤或肿瘤转移的方法，包括同时或依次向该患者施用治疗有效量的EGFR激酶抑制剂和一种能够使肿瘤细胞对EGFR激酶抑制剂产生敏感性的药物，其中该药物是一种能够结合并直接抑制mTORC1和mTORC2激酶的mTOR抑制剂。本发明还提供了一种制药组合物，包括一种EGFR激酶抑制剂和一种能够结合并直接抑制mTORC1和mTORC2激酶的mTOR抑制剂，以及药学上可接受的载体。本发明中可用于实施该方法的EGFR激酶抑制剂的首选例子是厄洛替尼盐酸盐（也称为TARCEVA®）。
• Combined Treatment with an EGFR Kinase Inhibitor and an Agent that Sensitizes Tumor Cells to the Effects of EGFR Kinase Inhibitors
  申请人：Buck Elizabeth A.

  公开号：US20120207767A1

  公开（公告）日：2012-08-16

  The present invention provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein said agent is an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases. The present invention also provides a pharmaceutical composition comprising an EGFR kinase inhibitor and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases, in a pharmaceutically acceptable carrier. A preferred example of an EGFR kinase inhibitor that can be used in practicing the methods of this invention is the compound erlotinib HCl (also known as TARCEVA®).

  本发明提供了一种治疗患者肿瘤或肿瘤转移的方法，包括向该患者同时或顺序给予治疗有效量的EGFR激酶抑制剂和一种能够使肿瘤细胞对EGFR激酶抑制剂的影响更敏感的药物，其中该药物是一种mTOR抑制剂，能够结合并直接抑制mTORC1和mTORC2激酶。本发明还提供了一种制药组合物，包括一种EGFR激酶抑制剂和一种mTOR抑制剂，能够结合并直接抑制mTORC1和mTORC2激酶，以及药学上可接受的载体。本发明中可用于实施该方法的EGFR激酶抑制剂的优选示例是化合物依洛替尼盐酸盐（也称为TARCEVA®）。
• US8114846B2
  申请人：——

  公开号：US8114846B2

  公开（公告）日：2012-02-14