(R)-ethyl 3-chloro-5-cyclopentyl-6-ethyl-5,6-dihydroimidazo[1,5-f]pteridine-7-carboxylate | 1035204-54-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 英文名称: (R)-ethyl 3-chloro-5-cyclopentyl-6-ethyl-5,6-dihydroimidazo[1,5-f]pteridine-7-carboxylate
• 英文别名: ethyl (6R)-3-chloro-5-cyclopentyl-6-ethyl-6H-imidazo[1,5-f]pteridine-7-carboxylate
• CAS: 1035204-54-6
• 化学式: C₁₈H₂₂ClN₅O₂
• 分子量: 375.858
• InChiKey: LBRDMGJXHJZNSS-GFCCVEGCSA-N

物化性质

• 沸点：
  585.8±50.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  73.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-ethyl 3-chloro-5-cyclopentyl-6-ethyl-5,6-dihydroimidazo[1,5-f]pteridine-7-carboxylate 在 盐酸 、 氨 、 氯化铵 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 生成 (6R)-5-cyclopentyl-6-ethyl-3-[2-methoxy-4-[(1-methylpiperidin-4-yl)carbamoyl]anilino]-6H-imidazo[1,5-f]pteridine-7-carboxamide
  参考文献：
  名称：

  Structure-based design and SAR development of 5,6-dihydroimidazolo[1,5-f]pteridine derivatives as novel Polo-like kinase-1 inhibitors

  摘要：

  Using structure-based drug design, we identified a novel series of 5,6-dihydroimidazolo[1,5-f]Apteridine PLK1 inhibitors. Rational improvements to compounds of this class resulted in single-digit nanomolar enzyme and cellular activity against PLK1, and oral bioavailability. Compound 1 exhibits > 7 fold induction of phosphorylated Histone H3 and is efficacious in an in vivo HT-29 tumor xenograft model. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.10.009
• 作为产物：
  描述：

  (2R)-2-(环戊氨基)-丁酸甲酯 在 亚磷酸三苯酯 、 ammonium vanadate 、 platinum on carbon 、 氢气 、 sodium hydride 、 氯磷酸二乙酯 作用下， 以 四氢呋喃 为溶剂， -78.0~20.0 ℃ 、517.12 kPa 条件下， 反应 5.0h， 生成 (R)-ethyl 3-chloro-5-cyclopentyl-6-ethyl-5,6-dihydroimidazo[1,5-f]pteridine-7-carboxylate
  参考文献：
  名称：

  Structure-based design and SAR development of 5,6-dihydroimidazolo[1,5-f]pteridine derivatives as novel Polo-like kinase-1 inhibitors

  摘要：

  Using structure-based drug design, we identified a novel series of 5,6-dihydroimidazolo[1,5-f]Apteridine PLK1 inhibitors. Rational improvements to compounds of this class resulted in single-digit nanomolar enzyme and cellular activity against PLK1, and oral bioavailability. Compound 1 exhibits > 7 fold induction of phosphorylated Histone H3 and is efficacious in an in vivo HT-29 tumor xenograft model. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.10.009

文献信息

• [EN] DIHYDROIMIDAZO [ 1, 5-F] PTERIDINES AS POLO-LIKE KINASE INHIBITORS<br/>[FR] DIHYDROIMIDAZO [ 1, 5-F] PTÉRIDINES EN TANT QU'INHIBITEURS DE KINASES DE TYPE POLO (PLK)
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2010025073A1

  公开（公告）日：2010-03-04

  The present invention provides PLK inhibitors of the formula (I) wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using the compounds.

  本发明提供了具有以下式（I）的PLK抑制剂，其中变量如本文所定义。还提供了包括这种化合物的药物组合物、试剂盒和制造物品；用于制备这些化合物的有用中间体和方法；以及使用这些化合物的方法。
• COMPOUNDS USEFUL AS PROTEIN KINASE INHIBITORS
  申请人：Charrier Jean-Damien

  公开号：US20100099686A1

  公开（公告）日：2010-04-22

  The present invention relates to compounds useful as inhibitors of protein kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions.

  本发明涉及用作蛋白激酶抑制剂的化合物。本发明还提供了包括上述化合物的药学上可接受的组合物以及使用该组合物治疗各种疾病、病况或障碍的方法。本发明还提供了制备本发明化合物的方法。
• POLO-LIKE KINASE INHIBITORS
  申请人：Cao Sheldon X.

  公开号：US20100075973A1

  公开（公告）日：2010-03-25

  The present invention provides PLK inhibitors of the formula wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using the compounds.

  本发明提供了PLK抑制剂，其公式如下，其中变量的定义如本文所述。还提供了包含此类化合物的制药组合物、工具箱和制造品；制备该化合物的有用中间体和方法；以及使用该化合物的方法。
• WO2008/76392
  申请人：——

  公开号：——

  公开（公告）日：——
• US8129387B2
  申请人：——

  公开号：US8129387B2

  公开（公告）日：2012-03-06