acetic acid 4-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-6-methoxy-pyrrolo[2,1-f][1,2,4]triazin-5-ylmethyl ester | 934832-08-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: acetic acid 4-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-6-methoxy-pyrrolo[2,1-f][1,2,4]triazin-5-ylmethyl ester
• CAS: 934832-08-3
• 化学式: C₂₄H₂₁FN₆O₃
• 分子量: 460.468
• InChiKey: FFXQPDXXYDSETM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.08
• 重原子数：
  34.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  95.57
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  acetic acid 4-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-6-methoxy-pyrrolo[2,1-f][1,2,4]triazin-5-ylmethyl ester 在 三氟乙酸 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 18.0h， 生成 N-[1-[(3-fluorophenyl)methyl]indazol-5-yl]-6-methoxy-5-[[(2S)-morpholin-2-yl]methoxymethyl]pyrrolo[2,1-f][1,2,4]triazin-4-amine
  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：

  在 lithium aluminium tetrahydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 acetic acid 4-[1-(3-fluoro-benzyl)-1H-indazol-5-ylamino]-6-methoxy-pyrrolo[2,1-f][1,2,4]triazin-5-ylmethyl 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

• 5-((4-Aminopiperidin-1-yl)methyl)pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases
  作者：Harold Mastalerz、Ming Chang、Ping Chen、Brian E. Fink、Ashvinikumar Gavai、Wen-Ching Han、Walter Johnson、David Langley、Francis Y. Lee、Kenneth Leavitt、Punit Marathe、Derek Norris、Simone Oppenheimer、Bogdan Sleczka、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.2007.06.019

  日期：2007.9

  Pyrrolotriazine dual EGFR/HER2 kinase inhibitors with a 5-((4-aminopiperidin-1-yl)methyl) solubilizing group were found to be superior to analogs with previously reported C-5 solubilizing groups. New synthetic methodology was developed for the parallel synthesis of C-4 analogs with the new solubilizing group. Interesting new leads were evaluated in tumor xenograft models and the C-4 aminofluorobenzylindazole, le, was found to exhibit the best antitumor activity. It is hypothesized that this solubilizing group extends into the ribose-phosphate portion of the ATP binding pocket and enhances the binding affinity of the inhibitor. (C) 2007 Elsevier Ltd. All rights reserved.
• Novel C-5 aminomethyl pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases
  作者：Harold Mastalerz、Ming Chang、Ashvinikumar Gavai、Walter Johnson、David Langley、Francis Y. Lee、Punit Marathe、Arvind Mathur、Simone Oppenheimer、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.2007.02.050

  日期：2007.5

  Novel C-5 aminomethyl pyrrolotriazines were prepared and optimized for dual EGFR and HER2 protein tyrosine kinase inhibition. The homopiperazine, 1p, emerged as a key lead and it showed promising oral efficacy in EGFR and dual EGFR/HER2 driven human tumor xenograft models. It is hypothesized that the C-5 homopiperazine side chain binds in the ribose-phosphate portion of the ATP binding pocket. (c) 2007 Elsevier Ltd. All rights reserved.