2-chloro-7,7-difluoro-9-isopropyl-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one | 1137870-04-2

• 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: 2-chloro-7,7-difluoro-9-isopropyl-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one
• 英文别名: 2-chloro-7,7-difluoro-9-isopropyl-5-methyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one；2-Chloro-7,7-difluoro-9-isopropyl-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one；2-chloro-7,7-difluoro-5-methyl-9-propan-2-yl-8H-pyrimido[4,5-b][1,4]diazepin-6-one
• CAS: 1137870-04-2
• 化学式: C₁₁H₁₃ClF₂N₄O
• 分子量: 290.7
• InChiKey: VSWUXJWUEXNGLF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  49.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-chloro-7,7-difluoro-9-isopropyl-5-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 、 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 30.0h， 生成 4-(7,7-difluoro-9-isopropyl-5-methyl-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
  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
• 作为产物：
  描述：

  ethyl 2,2-difluoro-3-(isopropylamino)propanoate 在 铁粉 、 碳酸氢钠 、 caesium carbonate 、 溶剂黄146 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 2-chloro-7,7-difluoro-9-isopropyl-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one
  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

• HALO-SUBSTITUTED PYRIMIDODIAZEPINES
  申请人：Cai Jianping

  公开号：US20090318408A1

  公开（公告）日：2009-12-24

  The present invention provides PLK1 inhibitor compounds of formula I: useful in the treatment or control of cell proliferative disorders, particularly oncological disorders. These compounds and formulations containing such compounds may be useful in the treatment or control of solid tumors, such as, for example, breast, colon, lung and prostate tumors and other oncological diseases such as non-Hodgkin's lymphomas. Also provided are intermediate compounds useful in the synthesis of compounds of formula I.

  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，例如乳腺癌、结肠癌、肺癌和前列腺癌等固体肿瘤，以及非霍奇金淋巴瘤等其他肿瘤性疾病。还提供了在合成公式I化合物中有用的中间体化合物。
• POLO-LIKE KINASE INHIBITORS
  申请人：Cao Sheldon X.

  公开号：US20090281092A1

  公开（公告）日：2009-11-12

  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：其中变量如本文所定义。还提供了包含这些化合物的制药组合物、工具包和制造品；用于制备这些化合物的方法和中间体；以及使用这些化合物的方法。
• Halo-substituted pyrimidodiazepines
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US08003785B2

  公开（公告）日：2011-08-23

  The present invention provides PLK1 inhibitor compounds of formula I: useful in the treatment or control of cell proliferative disorders, particularly oncological disorders. These compounds and formulations containing such compounds may be useful in the treatment or control of solid tumors, such as, for example, breast, colon, lung and prostate tumors and other oncological diseases such as non-Hodgkin's lymphomas. Also provided are intermediate compounds useful in the synthesis of compounds of formula I.

  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对实体瘤的治疗或控制有用，例如乳腺癌、结肠癌、肺癌和前列腺癌等肿瘤，以及非霍奇金淋巴瘤等其他肿瘤性疾病。还提供了用于合成公式I化合物的中间体化合物。
• Polo-like kinase inhibitors
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US08318727B2

  公开（公告）日：2012-11-27

  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：其中变量的定义如本文所述。还提供了包含这些化合物的药物组合物、试剂盒和制品；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。
• [EN] POLO-LIKE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASE DE TYPE POLO
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2009042711A4

  公开（公告）日：2009-06-04