2-chloro-7,7-difluoro-9-phenethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one | 1201693-77-7

• 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-phenethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one
• 英文别名: 2-Chloro-7,7-difluoro-9-phenethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one；2-chloro-7,7-difluoro-9-(2-phenylethyl)-5,8-dihydropyrimido[4,5-b][1,4]diazepin-6-one
• CAS: 1201693-77-7
• 化学式: C₁₅H₁₃ClF₂N₄O
• 分子量: 338.744
• InChiKey: WFEKUWLXTCRVQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  58.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-chloro-7,7-difluoro-9-phenethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one 在 盐酸 、 caesium carbonate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 4-(7,7-difluoro-5-methyl-6-oxo-9-phenethyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-benzoic acid
  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：

  3-[(2-chloro-5-nitro-pyrimidin-4-yl)-phenethyl-amino]-2,2-difluoro-propionic acid ethyl ester 在 铁粉 水 、 乙酸乙酯 、 ammonium hydroxide 、 magnesium sulfate 、 正己烷 作用下， 以 溶剂黄146 为溶剂， 反应 2.17h， 以gave 0.65 g of 2-chloro-7,7-difluoro-9-phenethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-275)的产率得到2-chloro-7,7-difluoro-9-phenethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one
  参考文献：
  名称：

  Halo-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。

  公开号：

  US08003785B2

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。
• HALO-SUBSTITUTED PYRIMIDODIAZEPINES AS PLKL INHIBITORS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2303889A1

  公开（公告）日：2011-04-06
• US8003785B2
  申请人：——

  公开号：US8003785B2

  公开（公告）日：2011-08-23
• [EN] HALO-SUBSTITUTED PYRIMIDODIAZEPINES AS PLKL INHIBITORS<br/>[FR] PYRIMIDODIAZÉPINES À SUBSTITUTION HALOGÉNO EN TANT QU'INHIBITEURS DE PLKL
  申请人：HOFFMANN LA ROCHE

  公开号：WO2009153197A1

  公开（公告）日：2009-12-23

  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).
• Identification of novel, potent and selective inhibitors of Polo-like kinase 1
  作者：Shaoqing Chen、David Bartkovitz、Jianping Cai、Yi Chen、Zhi Chen、Xin-Jie Chu、Kang Le、Nam T. Le、Kin-Chun Luk、Steve Mischke、Goli Naderi-Oboodi、John F. Boylan、Tom Nevins、Weiguo Qing、Yingsi Chen、Peter M. Wovkulich

  DOI：10.1016/j.bmcl.2011.11.052

  日期：2012.1

  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.