4-[(4R/S)-(2-cyclopentyl-4,6-dimethyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-3-methoxy-N-(1-methyl-4-piperidyl)benzamide | 946822-72-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 嘧啶二氮卓类
• 英文名称: 4-[(4R/S)-(2-cyclopentyl-4,6-dimethyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-3-methoxy-N-(1-methyl-4-piperidyl)benzamide
• 英文别名: (rac)-4-(9-cyclopentyl-5,7-dimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide；4-(9-cyclopentyl-6,7,8,9-tetrahydro-5,7-dimethyl-6-oxo-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide；4-(9-cyclopentyl-5,7-dimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide；4-[(9-cyclopentyl-5,7-dimethyl-6-oxo-7,8-dihydropyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide
• CAS: 946822-72-6
• 化学式: C₂₈H₃₉N₇O₃
• 分子量: 521.663
• InChiKey: HGIQFVGANLZKQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-[(4R/S)-(2-cyclopentyl-4,6-dimethyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-3-methoxy-N-(1-methyl-4-piperidyl)benzamide 生成 4-[[(4S)-2-cyclopentyl-4,6-dimethyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl]amino]-3-methoxy-N-(1-methyl-4-piperidyl)benzamide 、 4-[[(4R)-2-cyclopentyl-4,6-dimethyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl]amino]-3-methoxy-N-(1-methyl-4-piperidyl)benzamide
  参考文献：
  名称：

  SUBSTITUTED PYRIMIDODIAZEPINES

  摘要：

  本发明提供了公式I的PLK1抑制剂化合物： 用于治疗或控制细胞增殖性疾病，特别是肿瘤性疾病。这些化合物和含有这些化合物的配方可能在治疗或控制实体肿瘤方面有用，例如乳腺、结肠、肺和前列腺肿瘤以及其他肿瘤性疾病，如非霍奇金淋巴瘤。

  公开号：

  US20080234255A1
• 作为产物：
  描述：

  (rac)-2-chloro-9-cyclopentyl-7-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one 在 盐酸 、 O-Benzotriazol-1-yl-N,N,N',N'-bis(tetramethylene)uronium hexafluorophosphate 、 caesium carbonate 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 4-[(4R/S)-(2-cyclopentyl-4,6-dimethyl-5-oxo-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-10-yl)amino]-3-methoxy-N-(1-methyl-4-piperidyl)benzamide
  参考文献：
  名称：

  Identification of novel, potent and selective inhibitors of Polo-like kinase 1

  摘要：

  A series of pyrimidodiazepines was identified as potent Polo-like kinase 1 (PLK1) inhibitors. The synthesis and SAR are discussed. The lead compound 7 (RO3280) has potent inhibitory activity against PLK1, good selectivity against other kinases, and excellent in vitro cellular potency. It showed strong antitumor activity in xenograft mouse models. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.052

文献信息

• NOVEL COMPOUNDS
  申请人：HALSALL Christopher Thomas

  公开号：US20080009482A1

  公开（公告）日：2008-01-10

  There is provided a compound of formula (I): processes for the manufacture thereof, pharmaceutical compositions thereof and uses in therapy.

  提供了一个化合物的化学式(I)： 其制备方法，药物组合物以及在治疗中的用途。
• Dihydrodiazepines useful as inhibitors of protein kinases
  申请人：Kay David

  公开号：US20080167289A1

  公开（公告）日：2008-07-10

  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.

  本发明涉及一种作为蛋白激酶抑制剂的化合物。该发明还提供包含所述化合物的药用合适组合物，并提供使用这些组合物在治疗各种疾病、状况或障碍中的方法。该发明还提供制备本发明化合物的方法。
• [EN] METHODS FOR PREPARING PYRIMIDINE DERIVATIVES USEFUL AS PROTEIN KINASE INHIBITORS<br/>[FR] PROCÉDÉS DE PRÉPARATION DE DÉRIVÉS DE PYRIMIDINE UTILES COMME INHIBITEURS DE LA PROTÉINE KINASE
  申请人：VERTEX PHARMA

  公开号：WO2011036566A1

  公开（公告）日：2011-03-31

  A method of preparing a compound represented by Structural Formula (I), or a pharmaceutically acceptable salt thereof, wherein the variables of Structural Formula (I) are as described in the specification and claims, comprises the steps of: a) reacting a compound represented by Structural Formula (A) with FTNR1R7 under suitable conditions to form a compound represented by Structural Formula (B); and b) i) when R12 is -NO2, and R11 is -OR14: 1) cyclizing the compound represented by Structural Formula (B) under suitable cyclisation conditions to form a compound represented by Structural Formula (II); and 2) optionally reacting the compound represented by Structural Formula (II) with R9-LG2, wherein LG2 is a suitable leaving group, to form the compound represented by Structural Formula (I), wherein R8 is R9; or ii) when R12 is halogen, and R11 is -NHR13: 1) cyclizing the compound represented by Structural Formula (B) under suitable cyclisation conditions to form the compound represented by Structural Formula (I); and 2) optionally, when R13 is - H, reacting the compound produced from step b), ii), 1) with R9-LG2, wherein LG2 is a suitable leaving group, to form the compound represented by Structural Formula (I) wherein R8 is R9.

  一种制备化合物结构式（I）或其药学上可接受的盐的方法，其中结构式（I）中的变量如说明书和权利要求中所述，包括以下步骤：a）在适当的条件下，将化合物结构式（A）与FTNR1R7反应，形成化合物结构式（B）；和b）i）当R12为-N02，而R11为-OR14时：1）在适当的环化条件下，使化合物结构式（B）环化形成化合物结构式（II）；和2）可选择地将化合物结构式（II）与R9-LG2反应，其中LG2是适当的离去基团，形成化合物结构式（I），其中R8为R9；或ii）当R12为卤素，而R11为-NHR13时：1）在适当的环化条件下，使化合物结构式（B）环化形成化合物结构式（I）；和2）可选择地，当R13为-H时，将从步骤b）ii）1）产生的化合物与R9-LG2反应，其中LG2是适当的离去基团，形成化合物结构式（I），其中R8为R9。
• POLO-LIKE KINASE INHIBITORS
  申请人：Cao Sheldon X.

  公开号：US20090291938A1

  公开（公告）日：2009-11-26

  Compounds of the following formula are provided for use with kinases: 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 said compounds.

  提供了以下公式的化合物，用于与激酶一起使用：其中变量的定义如下。还提供了包含这些化合物的制药组合物、工具包和制造物品；用于制造这些化合物的方法和中间体；以及使用这些化合物的方法。
• DIHYDRODIAZEPINES USEFUL AS INHIBITORS OF PROTEIN KINASES
  申请人：Kay David

  公开号：US20100190765A1

  公开（公告）日：2010-07-29

  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.

  本发明涉及一种作为蛋白激酶抑制剂有用的化合物。该发明还提供包括所述化合物的药学上可接受的组合物，并且提供使用这些组合物治疗各种疾病、状况或障碍的方法。该发明还提供制备本发明化合物的方法。