methyl (S)-4-(5-(1-methylpiperidin-4-yloxy)-1H-benzo[d]imidazol-1-yl)-2-(1-(2-(trifluoromethyl)phenyl)ethoxy)benzoate | 1276687-87-6

• 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 (S)-4-(5-(1-methylpiperidin-4-yloxy)-1H-benzo[d]imidazol-1-yl)-2-(1-(2-(trifluoromethyl)phenyl)ethoxy)benzoate
• CAS: 1276687-87-6
• 化学式: C₃₀H₃₀F₃N₃O₄
• 分子量: 553.581
• InChiKey: UINBPWLEWWQQFP-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.44
• 重原子数：
  40.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  65.82
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl (S)-4-(5-(1-methylpiperidin-4-yloxy)-1H-benzo[d]imidazol-1-yl)-2-(1-(2-(trifluoromethyl)phenyl)ethoxy)benzoate 在 氨 作用下， 以 甲醇 为溶剂， 反应 168.0h， 以100%的产率得到(S)-4-(5-(1-methylpiperidin-4-yloxy)-1H-benzo[d]imidazol-1-yl)-2-(1-(2-(trifluoromethyl)phenyl)ethoxy)benzamide
  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：

  methyl (S)-4-nitro-2-(1-(2-(trifluoromethyl)phenyl)ethoxy)benzoate 在 tris-(dibenzylideneacetone)dipalladium(0) 、 偶氮二甲酸二叔丁酯 、 palladium 10% on activated carbon 、 氢气 、 4-甲基苯磺酸吡啶 、 三乙酰氧基硼氢化钠 、 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 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 3.5h， 生成 methyl (S)-4-(5-(1-methylpiperidin-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