(2S,4S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-fluoropyrrolidine-2-carboxylic acid | 1001354-43-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,4S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-fluoropyrrolidine-2-carboxylic acid
• 英文别名: (2S,4S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-4-fluoropyrrolidine-2-carboxylic acid
• CAS: 1001354-43-3
• 化学式: C₁₇H₁₈FN₇O₂
• 分子量: 371.374
• InChiKey: MLEVCUBGICCPPR-GWCFXTLKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2S,4S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-fluoropyrrolidine-2-carboxylic acid 在 异丙基氯化镁 、 乙酰氯 作用下， 以 四氢呋喃 为溶剂， 生成 (2S,4S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-fluoro-N-(pyridazin-4-yl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Biochemical and transcriptional profiling to triage additional activities in a series of IGF-1R/IR inhibitors

  摘要：

  Therapeutic development of a targeted agent involves a series of decisions over additional activities that may be ignored, eliminated or pursued. This paper details the concurrent application of two methods that provide a spectrum of information about the biological activity of a compound: biochemical profiling on a large panel of kinase assays and transcriptional profiling of mRNA responses. Our mRNA profiling studies used a full dose range, identifying subsets of transcriptional responses with differing EC(50)s which may reflect distinct targets. Profiling data allowed prioritization for validation in xenograft models, generated testable hypotheses for active compounds, and informed decisions on the general utility of the series. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.090
• 作为产物：
  描述：

  2-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine 、 (2S,4S)-4-氟吡咯烷-2-羧酸盐酸盐 在 N,N-二异丙基乙胺 、 sodium hydroxide 、 盐酸 作用下， 以 N-甲基吡咯烷酮 、 水 为溶剂， 反应 72.0h， 生成 (2S,4S)-1-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-fluoropyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  Biochemical and transcriptional profiling to triage additional activities in a series of IGF-1R/IR inhibitors

  摘要：

  Therapeutic development of a targeted agent involves a series of decisions over additional activities that may be ignored, eliminated or pursued. This paper details the concurrent application of two methods that provide a spectrum of information about the biological activity of a compound: biochemical profiling on a large panel of kinase assays and transcriptional profiling of mRNA responses. Our mRNA profiling studies used a full dose range, identifying subsets of transcriptional responses with differing EC(50)s which may reflect distinct targets. Profiling data allowed prioritization for validation in xenograft models, generated testable hypotheses for active compounds, and informed decisions on the general utility of the series. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.090

文献信息

• PYRROLOTRIAZINE KINASE INHIBITORS
  申请人：Wittman Mark D.

  公开号：US20080009497A1

  公开（公告）日：2008-01-10

  The invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity thereby making them useful as anticancer agents and for the treatment of Alzheimer's Disease.

  本发明提供了公式I的化合物以及药用可接受的盐类。公式I的化合物通过抑制酪氨酸激酶活性，使其可作为抗癌剂以及用于治疗阿尔茨海默病。
• US7534792B2
  申请人：——

  公开号：US7534792B2

  公开（公告）日：2009-05-19
• US7879855B2
  申请人：——

  公开号：US7879855B2

  公开（公告）日：2011-02-01
• US8263765B2
  申请人：——

  公开号：US8263765B2

  公开（公告）日：2012-09-11