2-(4-methylsulfanylpyrrolo[2,1-f][1,2,4]triazin-5-ylmethoxymethyl)morpholine-4-carboxylic acid tert-butyl ester | 859854-64-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 2-(4-methylsulfanylpyrrolo[2,1-f][1,2,4]triazin-5-ylmethoxymethyl)morpholine-4-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (2S)-2-[(4-methylsulfanylpyrrolo[2,1-f][1,2,4]triazin-5-yl)methoxymethyl]morpholine-4-carboxylate
• CAS: 859854-64-1
• 化学式: C₁₈H₂₆N₄O₄S
• 分子量: 394.495
• InChiKey: UUGHMAYMCUMAIX-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(4-methylsulfanylpyrrolo[2,1-f][1,2,4]triazin-5-ylmethoxymethyl)morpholine-4-carboxylic acid tert-butyl ester 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (S)-2-{4-[3-chloro-4-(3-fluoro-benzyloxy)-5 phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-5-ylmethoxy methyl}-morpholine-4-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  New C-5 substituted pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases

  摘要：

  Novel C-5 substituted pyrrolotriazines were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The lead compound exhibited promising oral efficacy in both EGFR and HER2 driven human tumor xenograft models. It is hypothesized that its C-5 morpholine side chain binds in the ribose phosphate portion of the ATP binding pocket. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.002
• 作为产物：
  描述：

  4-氯-5-甲基吡咯并[2,1-f][1,2,4]三嗪 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 四氯化碳 、 甲苯 为溶剂， 反应 0.17h， 生成 2-(4-methylsulfanylpyrrolo[2,1-f][1,2,4]triazin-5-ylmethoxymethyl)morpholine-4-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  New C-5 substituted pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases

  摘要：

  Novel C-5 substituted pyrrolotriazines were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The lead compound exhibited promising oral efficacy in both EGFR and HER2 driven human tumor xenograft models. It is hypothesized that its C-5 morpholine side chain binds in the ribose phosphate portion of the ATP binding pocket. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.002

文献信息

• [EN] PYRROLOTRIAZINE COMPOUNDS AS KINASE INHIBITORS<br/>[FR] COMPOSES DE PYRROLOTRIAZINE SERVANT D'INHIBITEURS DE KINASES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2005066176A1

  公开（公告）日：2005-07-21

  The present invention provides compounds of formula (I); and pharmaceutically acceptable salts thereof. The formula (I) compounds inhibit tyrosine kinase activity of growth factor receptors such as HER1, HER2 and HER4 thereby making them useful as antiproliferative agents. The formula (I) compounds are also useful for the treatment of other diseases associated with signal transduction pathways operating through growth factor receptors.

  本发明提供了式（I）的化合物；以及其药学上可接受的盐。式（I）的化合物抑制生长因子受体如HER1、HER2和HER4的酪氨酸激酶活性，从而使它们作为抗增殖剂有用。式（I）的化合物还可用于治疗与通过生长因子受体进行的信号转导途径相关的其他疾病。
• PYRROLOTRIAZINE COMPOUNDS AS KINASE INHIBITORS
  申请人：Fink Brian E.

  公开号：US20110039838A1

  公开（公告）日：2011-02-17

  The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity of growth factor receptors such as HER1, HER2 and HER4 thereby making them useful as antiproliferative agents. The formula I compounds are also useful for the treatment of other diseases associated with signal transduction pathways operating through growth factor receptors.

  本发明提供了I式化合物及其药学上可接受的盐。I式化合物抑制生长因子受体的酪氨酸激酶活性，如HER1、HER2和HER4，因此使它们成为抗增殖剂。I式化合物也可用于治疗与通过生长因子受体进行信号转导途径相关的其他疾病。
• Pyrrolotriazine compounds as kinase inhibitors
  申请人：Bristol-Myers Squibb Company

  公开号：EP2058314A1

  公开（公告）日：2009-05-13

  The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity of growth factor receptors such as HER1, HER2 and HER4 thereby making them useful as antiproliferative agents. The formula I compounds are also useful for the treatment of other diseases associated with signal transduction pathways operating through growth factor receptors.

  本发明提供了式 I 的化合物 及其药学上可接受的盐类。 式 I 化合物可抑制生长因子受体（如 HER1、HER2 和 HER4）的酪氨酸激酶活性，因此可用作抗增殖剂。式 I 化合物还可用于治疗与通过生长因子受体运行的信号转导通路相关的其他疾病。
• Novel pyrrolo[2,1-f][1,2,4]triazin-4-amines: Dual inhibitors of EGFR and HER2 protein tyrosine kinases
  作者：Brian E. Fink、Derek Norris、Harold Mastalerz、Ping Chen、Bindu Goyal、Yufen Zhao、Soong-Hoon Kim、Gregory D. Vite、Francis Y. Lee、Hongjian Zhang、Simone Oppenheimer、John S. Tokarski、Tai W. Wong、Ashvinikumar V. Gavai

  DOI：10.1016/j.bmcl.2010.11.100

  日期：2011.1

  A novel series of 5-((4-aminopiperidin-1-yl) methyl)-pyrrolo[ 2,1-f][ 1,2,4] triazin-4-amines with small aniline substituents at the C4 position were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. Compound 81 exhibited promising oral efficacy in both EGFR and HER2-driven human tumor xenograft models. (C) 2010 Elsevier Ltd. All rights reserved.
• New C-5 substituted pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases
  作者：Harold Mastalerz、Ming Chang、Ping Chen、Pierre Dextraze、Brian E. Fink、Ashvinikumar Gavai、Bindu Goyal、Wen-Ching Han、Walter Johnson、David Langley、Francis Y. Lee、Punit Marathe、Arvind Mathur、Simone Oppenheimer、Edward Ruediger、James Tarrant、John S. Tokarski、Gregory D. Vite、Dolatrai M. Vyas、Henry Wong、Tai W. Wong、Hongjian Zhang、Guifen Zhang

  DOI：10.1016/j.bmcl.2007.01.002

  日期：2007.4

  Novel C-5 substituted pyrrolotriazines were optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The lead compound exhibited promising oral efficacy in both EGFR and HER2 driven human tumor xenograft models. It is hypothesized that its C-5 morpholine side chain binds in the ribose phosphate portion of the ATP binding pocket. (c) 2007 Elsevier Ltd. All rights reserved.