methyl (+/-)-4-(5-hydroxy-1H-benzo[d]imidazol-1-yl)-2-(1-(2-(trifluoromethyl)phenyl)ethoxy)benzoate | 1276687-64-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: methyl (+/-)-4-(5-hydroxy-1H-benzo[d]imidazol-1-yl)-2-(1-(2-(trifluoromethyl)phenyl)ethoxy)benzoate
• 英文别名: Methyl 4-(5-hydroxybenzimidazol-1-yl)-2-[1-[2-(trifluoromethyl)phenyl]ethoxy]benzoate
• CAS: 1276687-64-9
• 化学式: C₂₄H₁₉F₃N₂O₄
• 分子量: 456.421
• InChiKey: KDYCUHXKBSGZSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  73.6
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl (+/-)-4-(5-hydroxy-1H-benzo[d]imidazol-1-yl)-2-(1-(2-(trifluoromethyl)phenyl)ethoxy)benzoate 在 偶氮二甲酸二叔丁酯 、 三苯基膦 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 methyl 4-(5-(piperidin-4-yloxy)-1H-benzo[d]imidazol-1-yl)-2-(1-(2-(trifluoromethyl)phenyl)ethoxy)benzoate
  参考文献：
  名称：

  Benzimidazole Inhibitors Induce a DFG-Out Conformation of Never in Mitosis Gene A-Related Kinase 2 (Nek2) without Binding to the Back Pocket and Reveal a Nonlinear Structure−Activity Relationship

  摘要：

  We describe herein the structure-activity relationship (SAR) and cocrystal structures of a series of Nek2 inhibitors derived from the published polo-like kinase 1 (Plk1) inhibitor (R)-1. Our studies reveal a nonlinear SAR for Nek2 and our cocrystal structures show that compounds in this series bind to a DFG-out conformation of Nek2 without extending into the enlarged back pocket commonly found in this conformation. These observations were further investigated, and structure-based design led to Nek2 inhibitors derived from (R)-1 with more than a hundred-fold selectivity against Plk1.

  DOI：

  10.1021/jm1011726
• 作为产物：
  描述：

  2-羟基-4-硝基苯甲酸甲酯 在 tris-(dibenzylideneacetone)dipalladium(0) 、 偶氮二甲酸二叔丁酯 、 氢气 、 4-甲基苯磺酸吡啶 、 铁粉 、 caesium carbonate 、 溶剂黄146 、 三苯基膦 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 20.75h， 生成 methyl (+/-)-4-(5-hydroxy-1H-benzo[d]imidazol-1-yl)-2-(1-(2-(trifluoromethyl)phenyl)ethoxy)benzoate
  参考文献：
  名称：

  Benzimidazole Inhibitors Induce a DFG-Out Conformation of Never in Mitosis Gene A-Related Kinase 2 (Nek2) without Binding to the Back Pocket and Reveal a Nonlinear Structure−Activity Relationship

  摘要：

  We describe herein the structure-activity relationship (SAR) and cocrystal structures of a series of Nek2 inhibitors derived from the published polo-like kinase 1 (Plk1) inhibitor (R)-1. Our studies reveal a nonlinear SAR for Nek2 and our cocrystal structures show that compounds in this series bind to a DFG-out conformation of Nek2 without extending into the enlarged back pocket commonly found in this conformation. These observations were further investigated, and structure-based design led to Nek2 inhibitors derived from (R)-1 with more than a hundred-fold selectivity against Plk1.

  DOI：

  10.1021/jm1011726

文献信息

• Benzimidazole Inhibitors Induce a DFG-Out Conformation of Never in Mitosis Gene A-Related Kinase 2 (Nek2) without Binding to the Back Pocket and Reveal a Nonlinear Structure−Activity Relationship
  作者：Savade Solanki、Paolo Innocenti、Corine Mas-Droux、Kathy Boxall、Caterina Barillari、Rob L. M. van Montfort、G. Wynne Aherne、Richard Bayliss、Swen Hoelder

  DOI：10.1021/jm1011726

  日期：2011.3.24

  We describe herein the structure-activity relationship (SAR) and cocrystal structures of a series of Nek2 inhibitors derived from the published polo-like kinase 1 (Plk1) inhibitor (R)-1. Our studies reveal a nonlinear SAR for Nek2 and our cocrystal structures show that compounds in this series bind to a DFG-out conformation of Nek2 without extending into the enlarged back pocket commonly found in this conformation. These observations were further investigated, and structure-based design led to Nek2 inhibitors derived from (R)-1 with more than a hundred-fold selectivity against Plk1.