N-(3-(4-aminophenyl)-1H-pyrazol-5-yl)-4-(2-(pyrrolidin-1-yl)ethoxy)benzamide | 1391621-85-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(3-(4-aminophenyl)-1H-pyrazol-5-yl)-4-(2-(pyrrolidin-1-yl)ethoxy)benzamide
• CAS: 1391621-85-4
• 化学式: C₂₂H₂₅N₅O₂
• 分子量: 391.473
• InChiKey: XJANGVUPJVLZQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.39
• 重原子数：
  29.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  96.27
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-(3-(4-aminophenyl)-1H-pyrazol-5-yl)-4-(2-(pyrrolidin-1-yl)ethoxy)benzamide 、 氯甲酸苯酯 在 吡啶 作用下， 生成 phenyl-N-[4-(5-[4-(2-tetrahydro-1H-1-pyrrolylethoxy)benzoyl]amino-1H-3-pyrazolyl)phenyl]carbamate
  参考文献：
  名称：

  3-Phenyl-1H-5-pyrazolylamine-based derivatives as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3)

  摘要：

  A new class of FLT3 inhibitors has been identified based on the 3-phenyl-1H-5-pyrazolylamine scaffold. The structure-activity relationships led to the discovery of two carbamate series, and some potent compounds within these two series exhibited better growth inhibition of FLT3-mutated MOLM-13 cells than FLT3 inhibitors sorafenib (2) and ABT-869 (3). In particular, compound 8d exhibited the ability to regress tumors in mouse xenograft model using MOLM-13 cells. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.05.116
• 作为产物：
  描述：

  在 盐酸 、 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 生成 N-(3-(4-aminophenyl)-1H-pyrazol-5-yl)-4-(2-(pyrrolidin-1-yl)ethoxy)benzamide
  参考文献：
  名称：

  3-Phenyl-1H-5-pyrazolylamine-based derivatives as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3)

  摘要：

  A new class of FLT3 inhibitors has been identified based on the 3-phenyl-1H-5-pyrazolylamine scaffold. The structure-activity relationships led to the discovery of two carbamate series, and some potent compounds within these two series exhibited better growth inhibition of FLT3-mutated MOLM-13 cells than FLT3 inhibitors sorafenib (2) and ABT-869 (3). In particular, compound 8d exhibited the ability to regress tumors in mouse xenograft model using MOLM-13 cells. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.05.116

文献信息

• Pyrazolylamine Derivatives Reveal the Conformational Switching between Type I and Type II Binding Modes of Anaplastic Lymphoma Kinase (ALK)
  作者：Chih-Hsiang Tu、Wen-Hsing Lin、Yi-Hui Peng、Tsu Hsu、Jian-Sung Wu、Chun-Yu Chang、Cheng-Tai Lu、Ping-Chiang Lyu、Chuan Shih、Weir-Torn Jiaang、Su-Ying Wu

  DOI：10.1021/acs.jmedchem.6b00106

  日期：2016.4.28

  anaplastic lymphoma kinase (ALK) inhibitors adopt a type I binding mode, but only limited type II ALK structural studies are available. Herein, we present the structure of ALK in complex with N1-(3-4-[([5-(tert-butyl)-3-isoxazolyl]aminocarbonyl)amino]-3-methylphenyl-1H-5-pyrazolyl)-4-[(4-methylpiperazino)methyl]benzamide (5a), a novel ALK inhibitor adopting a type II binding mode. It revealed binding

  大多数变性间变性淋巴瘤激酶（ALK）抑制剂采用I型结合模式，但仅有有限的II型ALK结构研究可用。在这里，我们介绍了与N 1-（3-4-[（[[（5-（叔丁基）-3-异恶唑基]氨基羰基）氨基] -3-甲基苯基-1 H -5-吡唑基）形成的ALK的结构。-4-[（4-甲基哌嗪子基）甲基]苯甲酰胺（5a），一种新型的ALK抑制剂，采用II型结合模式。揭示了5a的结合导致激活环，αC-螺旋和近膜结构域的构象变化和重新定位，它们都是ALK的自抑制机制和下游信号通路调控的重要结构域。结构-活性关系研究表明，对5a结构的修饰导致ALK效能显着不同，并改变了ALK的蛋白质结构。据我们所知，这是第一个直接观察小分子结构变化如何调节I型和II型结合模式之间的转换并诱导剧烈构象变化的结构生物学研究。