2-(2-(trifluoromethoxy)benzamido)-N-(6-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)thiazole-4-carboxamide | 1446200-49-2

• 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: 2-(2-(trifluoromethoxy)benzamido)-N-(6-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)thiazole-4-carboxamide
• 英文别名: 2-{[2-(Trifluoromethoxy)benzoyl]amino}-N-[6-(Trifluoromethyl)-1h-Benzimidazol-2-Yl]-1,3-Thiazole-4-Carboxamide；2-[[2-(trifluoromethoxy)benzoyl]amino]-N-[6-(trifluoromethyl)-1H-benzimidazol-2-yl]-1,3-thiazole-4-carboxamide
• CAS: 1446200-49-2
• 化学式: C₂₀H₁₁F₆N₅O₃S
• 分子量: 515.395
• InChiKey: GUWQZSKMUJFZMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  137
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2-(三氟甲氧基)苯甲酰氯 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.25h， 生成 2-(2-(trifluoromethoxy)benzamido)-N-(6-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)thiazole-4-carboxamide
  参考文献：
  名称：

  2-Benzamido-N-(1H-benzo[d]imidazol-2-yl)thiazole-4-carboxamide derivatives as potent inhibitors of CK1δ/ε

  摘要：

  In this study we identified two heterocyclic compounds (5 and 6) as potent and specific inhibitors of CK1 delta (IC50 = 0.040 and 0.042 mu M, respectively). Whereas compound 5 exhibited fivefold higher affinity towards CK1 delta than to CK1 epsilon (IC50 CK1 epsilon = 0.199 mu M), compound 6 also inhibited CK1 epsilon (IC50 = 0.0326 mu M) in the same range as CK1 delta. Selected compound 5 was screened over 442 kinases identifying 5 as a highly potent and selective inhibitor of CK1 delta. X-ray analysis of 5 bound to CK1 delta demonstrated its binding mode. In addition, characterization of 5 and 6 in a cell biological approach revealed the ability of both compounds to inhibit proliferation of tumor cell lines in a dose and cell line specific manner. In summary, our optimizations lead to the development of new highly selective CK1 delta and epsilon specific inhibitors with biological activity.

  DOI：

  10.1007/s00726-012-1234-x

文献信息

• 2-Benzamido-N-(1H-benzo[d]imidazol-2-yl)thiazole-4-carboxamide derivatives as potent inhibitors of CK1δ/ε
  作者：Joachim Bischof、Johann Leban、Mirko Zaja、Arnhild Grothey、Barbara Radunsky、Olaf Othersen、Stefan Strobl、Daniel Vitt、Uwe Knippschild

  DOI：10.1007/s00726-012-1234-x

  日期：2012.10

  In this study we identified two heterocyclic compounds (5 and 6) as potent and specific inhibitors of CK1 delta (IC50 = 0.040 and 0.042 mu M, respectively). Whereas compound 5 exhibited fivefold higher affinity towards CK1 delta than to CK1 epsilon (IC50 CK1 epsilon = 0.199 mu M), compound 6 also inhibited CK1 epsilon (IC50 = 0.0326 mu M) in the same range as CK1 delta. Selected compound 5 was screened over 442 kinases identifying 5 as a highly potent and selective inhibitor of CK1 delta. X-ray analysis of 5 bound to CK1 delta demonstrated its binding mode. In addition, characterization of 5 and 6 in a cell biological approach revealed the ability of both compounds to inhibit proliferation of tumor cell lines in a dose and cell line specific manner. In summary, our optimizations lead to the development of new highly selective CK1 delta and epsilon specific inhibitors with biological activity.