trans-4-[(3-amino-5-oxo-4,5-dihydro[1,2,4]triazin-6-ylmethyl)carbamoyl]cyclohexanecarboxylic acid methyl ester | 936902-00-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: trans-4-[(3-amino-5-oxo-4,5-dihydro[1,2,4]triazin-6-ylmethyl)carbamoyl]cyclohexanecarboxylic acid methyl ester
• 英文别名: methyl trans-4-{[(3-amino-5-oxo-4,5-dihydro-1,2,4-triazin-6-yl)methyl]carbamoyl}cyclohexanecarboxylate
• CAS: 936902-00-0
• 化学式: C₁₃H₁₉N₅O₄
• 分子量: 309.325
• InChiKey: HJJXBUMIFQWLLI-ZKCHVHJHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.66
• 重原子数：
  22.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  140.06
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  trans-4-[(3-amino-5-oxo-4,5-dihydro[1,2,4]triazin-6-ylmethyl)carbamoyl]cyclohexanecarboxylic acid methyl ester 在 1H-1,2,4-三唑 、 N-溴代丁二酰亚胺(NBS) 、 亚硝酸特丁酯 、 sodium carbonate 、 三氯氧磷 作用下， 以 四氢呋喃 、 吡啶 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 8.67h， 生成 OSI-027 tromethamine
  参考文献：
  名称：

  [EN] PROCESS FOR SUBSTITUTED 3-AMINO-5-OXO-4,5-DIHYDRO-[1,2,4]TRIAZINES
  [FR] PROCÉDÉ DE FABRICATION DE 3-AMINO-5-OXO-4,5-DIHYDRO-[1,2,4]TRIAZINES SUBSTITUÉES

  摘要：

  公开号：

  WO2011005909A3
• 作为产物：
  描述：

  二苄胺 在 palladium 10% on activated carbon 氢气 、 溶剂黄146 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 24.0h， 生成 trans-4-[(3-amino-5-oxo-4,5-dihydro[1,2,4]triazin-6-ylmethyl)carbamoyl]cyclohexanecarboxylic acid methyl ester
  参考文献：
  名称：

  [EN] PROCESS FOR SUBSTITUTED 3-AMINO-5-OXO-4,5-DIHYDRO-[1,2,4]TRIAZINES
  [FR] PROCÉDÉ DE FABRICATION DE 3-AMINO-5-OXO-4,5-DIHYDRO-[1,2,4]TRIAZINES SUBSTITUÉES

  摘要：

  公开号：

  WO2011005909A3

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®）。
• 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。
• SUBSTITUTED IMIDAZOPYR- AND IMIDAZOTRI-AZINES
  申请人：Crew Andrew P.

  公开号：US20090286768A1

  公开（公告）日：2009-11-19

  Fused pyridine-based bicyclic compounds having the structure of Formula I, as defined herein, pharmaceutically acceptable salts thereof, preparation, compositions, and disease treatment therewith. This abstract does not define or limit the invention.

  基于融合吡啶的双环化合物具有如下所定义的结构，其药学上可接受的盐，制备方法，组合物及其用于疾病治疗。本摘要不定义或限制该发明。
• Fused Bicyclic mTor Inhibitors
  申请人：Chen Xin

  公开号：US20090163468A1

  公开（公告）日：2009-06-25

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

  化合物式(I)或其药学上可接受的盐，是mTOR的抑制剂，可用于治疗癌症。
• 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。