6-aminomethyl-4,5-dihydro-3-methyl-1,2,4-triazin-5-one | 98750-24-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 6-aminomethyl-4,5-dihydro-3-methyl-1,2,4-triazin-5-one
• 英文别名: 6-aminomethyl-3-methyl-1,2,4-triazin-5(4H)-one；6-(aminomethyl)-3-methyl-1,2,4-triazin-5(4H)-one；6-(Aminomethyl)-3-methyl-1,2,4-triazin-5(4H)-one；6-(aminomethyl)-3-methyl-4H-1,2,4-triazin-5-one
• CAS: 98750-24-4
• 化学式: C₅H₈N₄O
• mdl: MFCD18073410
• 分子量: 140.145
• InChiKey: ISDURAWVACQPMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  79.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-aminomethyl-4,5-dihydro-3-methyl-1,2,4-triazin-5-one 在 palladium on activated charcoal 2-氯-1-甲基吡啶碘化物 、 氢气 、 三乙胺 作用下， 以 乙酸乙酯 、 乙腈 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 113.5h， 生成 2,5-anhydro-4,6-di-O-benzoyl-3-deoxy-N-<(4,5-dihydro-3-methyl-5-oxo-1,2,4-triazin-6-yl)methyl>-D-arabino- and -D-ribo-hexanamide
  参考文献：
  名称：

  咪唑并稠合的桥头氮的合成2'-脱氧核糖核苷酸Ç核苷：2,5-脱水-3,4,6-三-耦合消除反应ö苯甲酰基d-阿洛糖酸

  摘要：

  咪唑并稠合的桥头氮的短合成2'-脱氧Ç核苷已经研制成功。这是基于2,5-脱水-3,4,6-三-O-苯甲酰基-D-脲酸与一系列氨基烷基取代的杂环和醇的偶联消除反应。如此形成的中间体α，β-不饱和羧酰​​胺和酯被转化为新型咪唑并[1,5- a ]吡啶，咪唑并[1,5- b ]哒嗪和咪唑并[5,1- f ] [1,2， 4]三嗪-2'-脱氧ç核苷，包括2'-脱氧和2'-脱氧腺苷的类似物。核苷的异头构型的分配是基于质子nOe实验进行的。

  DOI：

  10.1039/p19850000621
• 作为产物：
  描述：

  3-methyl-6-phthalimidomethyl-1,2,4-triazin-5(4H)-one 在 肼 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 28.0h， 生成 6-aminomethyl-4,5-dihydro-3-methyl-1,2,4-triazin-5-one
  参考文献：
  名称：

  Fused bicyclic mTOR inhibitors

  摘要：

  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。

  公开号：

  US20070112005A1

文献信息

• 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 A. Elizabeth

  公开号：US20070280928A1

  公开（公告）日：2007-12-06

  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®).

  本发明提供了一种治疗患有非小细胞肺癌、胰腺癌、结肠癌或乳腺癌肿瘤或转移瘤的患者的方法，包括同时或顺序给患者施用治疗有效量的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作用的药物，其中该药物为mTOR抑制剂，可以加入其他抗癌药物或放疗等额外的药物或治疗方法。本发明还提供了一种治疗患者肿瘤或转移瘤的方法，包括同时或顺序给患者施用治疗有效量的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作用的药物，其中该药物为一种mTOR抑制剂，可结合并直接抑制mTORC1和mTORC2激酶。本发明还提供了一种制药组合物，包括一种EGFR激酶抑制剂和一种可结合并直接抑制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方法的EGFR激酶抑制剂的首选示例是化合物依洛替尼盐酸盐（也称为TARCEVA®）。
• Combination anti-cancer therapy
  申请人：Bhagwat Shripad

  公开号：US20090274698A1

  公开（公告）日：2009-11-05

  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 anti-cancer agent or treatment that elevates pAkt levels in tumor cells and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases. Examples of such anti-cancer agents or treatments include doxorubicin, cisplatin, or ionizing radiation. The present invention also provides a pharmaceutical composition comprising an anti-cancer agent or treatment that elevates pAkt levels in tumor cells and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases, in a pharmaceutically acceptable carrier. 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 the anti-cancer agent melphalan or 5-FU, and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases.

  本发明提供了一种治疗患者肿瘤或肿瘤转移的方法，包括同时或顺序给患者施用抗癌药物或提高肿瘤细胞pAkt水平的治疗剂量和结合并直接抑制mTORC1和mTORC2激酶的mTOR抑制剂。这样的抗癌药物或治疗剂包括多柔比星、顺铂或电离辐射。本发明还提供了一种药物组合，包括抗癌药物或提高肿瘤细胞pAkt水平的治疗剂量和结合并直接抑制mTORC1和mTORC2激酶的mTOR抑制剂，以及药学上可接受的载体。本发明还提供了一种治疗患者肿瘤或肿瘤转移的方法，包括同时或顺序给患者施用治疗剂量的抗癌药物美法仑或5-FU和结合并直接抑制mTORC1和mTORC2激酶的mTOR抑制剂。
• 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®）。
• FUSED BICYCLIC mTOR INHIBITORS
  申请人：Chen Xin

  公开号：US20130165651A1

  公开（公告）日：2013-06-27

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

  公式（I）所代表的化合物或其药学上可接受的盐，是mTOR的抑制剂，可用于癌症的治疗。