(R)-4-(7-cyano-6-ethyl-5-isopropyl-5,6-dihydroimidazo[1,5-f]pteridin-3-ylamino)-2-fluoro-5-methoxybenzoic acid | 1214265-80-1

• 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: (R)-4-(7-cyano-6-ethyl-5-isopropyl-5,6-dihydroimidazo[1,5-f]pteridin-3-ylamino)-2-fluoro-5-methoxybenzoic acid
• 英文别名: (R)-4-(5-isopropyl-7-cyano-6-ethyl-5,6-dihydroimidazo[1,5-f]pteridin-3-ylamino)-2-fluoro-5-methoxybenzoic acid；4-[[(6R)-7-cyano-6-ethyl-5-propan-2-yl-6H-imidazo[1,5-f]pteridin-3-yl]amino]-2-fluoro-5-methoxybenzoic acid
• CAS: 1214265-80-1
• 化学式: C₂₂H₂₂FN₇O₃
• 分子量: 451.46
• InChiKey: AMFKQXJWAQVQBP-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  129
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  4-氨基-1-甲基哌啶 、 (R)-4-(7-cyano-6-ethyl-5-isopropyl-5,6-dihydroimidazo[1,5-f]pteridin-3-ylamino)-2-fluoro-5-methoxybenzoic acid 在 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 N,N-二甲基甲酰胺 为溶剂， 生成 4-[[(6R)-7-cyano-6-ethyl-5-propan-2-yl-6H-imidazo[1,5-f]pteridin-3-yl]amino]-2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl)benzamide
  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：

  (R)-2-((2-氯-5-硝基嘧啶-4-基)(异丙基)氨基)丁酸甲酯 在 亚磷酸三苯酯 、 ammonium vanadate 、 N,N-二甲基乙酰胺 、 platinum on carbon 、 氢气 、 palladium diacetate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， -78.0~160.0 ℃ 、517.12 kPa 条件下， 反应 5.0h， 生成 (R)-4-(7-cyano-6-ethyl-5-isopropyl-5,6-dihydroimidazo[1,5-f]pteridin-3-ylamino)-2-fluoro-5-methoxybenzoic acid
  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。
• 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。