5,11-二氢-2-[[2-甲氧基-4-(4-甲基-1-哌嗪基)苯基]氨基]-11-甲基-6H-嘧啶并[4,5-b][1,4]苯并二氮杂卓-6-酮 | 1234480-46-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 5,11-二氢-2-[[2-甲氧基-4-(4-甲基-1-哌嗪基)苯基]氨基]-11-甲基-6H-嘧啶并[4,5-b][1,4]苯并二氮杂卓-6-酮
• 中文别名: 化合物XMD8-87；5,11-二氢-2-[[[2-甲氧基-4-(4-甲基-1-哌嗪基)苯基]氨基]-11-甲基-6H-嘧啶基[4,5-b][1,4]苯并二氮杂pin-6-1；TNK2抑制剂(XMD8-87)
• 英文名称: XMD-8-87
• 英文别名: 6H-Pyrimido[4,5-b][1,4]benzodiazepin-6-one, 5,11-dihydro-2-[[2-methoxy-4-(4-methyl-1-piperazinyl)phenyl]amino]-11-methyl-；2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-11-methyl-5H-pyrimido[4,5-b][1,4]benzodiazepin-6-one
• CAS: 1234480-46-6
• 化学式: C₂₄H₂₇N₇O₂
• 分子量: 445.524
• InChiKey: LGLHCXISMKHLIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  85.9
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-(甲基氨基)苯甲酸乙酯 在 Pd2dba3*CH2Cl2 、 铁粉 、 potassium carbonate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 叔丁醇 为溶剂， 反应 22.0h， 生成 5,11-二氢-2-[[2-甲氧基-4-(4-甲基-1-哌嗪基)苯基]氨基]-11-甲基-6H-嘧啶并[4,5-b][1,4]苯并二氮杂卓-6-酮
  参考文献：
  名称：

  Benzopyrimidodiazepinone inhibitors of TNK2

  摘要：

  The SAR of a series of benzopyrimidodiazepinone inhibitors of TNK2 was developed, starting from the potent and selective compound XMD8-87. A diverse set of anilines was introduced in an effort to improve the in vivo PK profile and minimize the risk of quinone diimine formation.

  DOI：

  10.1016/j.bmcl.2020.126948

文献信息

• [EN] INHIBITORS OF ACK1/TNK2 TYROSINE KINASE<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE ACK1/TNK2
  申请人：H LEE MOFFITT CANCER CT & RES

  公开号：WO2015021149A1

  公开（公告）日：2015-02-12

  Described are cancer therapies and anti-cancer compounds. In particular, disclosed are ihibitors of Ack1 tyrosine kinase and their use in the treatment of cancer. Methods of screening for new Ack1 tyrosine kinase inhibitors are also disclosed. In specifc example, compound having Formula I through IV are disclosed.

  描述了癌症治疗和抗癌化合物。特别是，披露了Ack1酪氨酸激酶的抑制剂及其在癌症治疗中的应用。还披露了筛选新的Ack1酪氨酸激酶抑制剂的方法。在具体示例中，披露了具有I至IV式的化合物。
• PYRIMIDO-DIAZEPINONE COMPOUNDS AND METHODS OF TREATING DISORDERS
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US20160024115A1

  公开（公告）日：2016-01-28

  The present invention relates to novel pyrimido-diazepinone compounds, methods of modulating protein kinases, including MPS1 (TTK), ERK5 (BMK1, MAPK7), LRKK2, EphA2, polo kinase 1,2,3, or 4, Ack1, Ack2, Abl, DCAMKL1, ABL1, Abl mutants, DCAMKL2, ARK5, BRK, MKNK2, FGFR4, TNK1, PLK1, ULK2, PLK4, PRKD1, PRKD2, PRKD3, ROS1, RPS6KA6, TAOK1, TAOK3, TNK2, Bcr-Abl, GAK, cSrc, TPR-Met, Tie2, MET, FGFR3, Aurora, Axl, Bmx, BTK, c-kit, CHK2, Flt3, MST2, p70S6K, PDGFR, PKB, PKC, Raf, ROCK-H, Rsk1, SGK, TrkA, TrkB and TrkC, and the use of such compounds in the treatment of various diseases, disorders or conditions.

  本发明涉及新型嘧啶二氮杂环庚内酮类化合物，调节蛋白激酶的方法，包括MPS1（TTK）、ERK5（BMK1，MAPK7）、LRKK2、EphA2、polo激酶1、2、3或4、Ack1、Ack2、Abl、DCAMKL1、ABL1、Abl突变体、DCAMKL2、ARK5、BRK、MKNK2、FGFR4、TNK1、PLK1、ULK2、PLK4、PRKD1、PRKD2、PRKD3、ROS1、RPS6KA6、TAOK1、TAOK3、TNK2、Bcr-Abl、GAK、cSrc、TPR-Met、Tie2、MET、FGFR3、Aurora、Axl、Bmx、BTK、c-kit、CHK2、Flt3、MST2、p70S6K、PDGFR、PKB、PKC、Raf、ROCK-H、Rsk1、SGK、TrkA、TrkB和TrkC等蛋白激酶的调节，以及这些化合物在治疗各种疾病、疾病或症状中的使用。
• INHIBITORS OF ACK1/TNK2 TYROSINE KINASE
  申请人：H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

  公开号：US20160176826A1

  公开（公告）日：2016-06-23

  Described are cancer therapies and anti-cancer compounds. In particular, disclosed are inhibitors of Ack1 tyrosine kinase and their use in the treatment of cancer. Methods of screening for new Ack1 tyrosine kinase inhibitors are also disclosed. In specific example, compound having Formula I through IV are disclosed.

  本文描述了癌症治疗和抗癌化合物。特别地，揭示了Ack1酪氨酸激酶抑制剂及其在癌症治疗中的应用。还披露了筛选新的Ack1酪氨酸激酶抑制剂的方法。具体例子中，揭示了具有I至IV式的化合物。
• PYRIMIDO-DIAZEPINONE KINASE SCAFFOLD COMPOUNDS AND METHODS OF TREATING DISORDERS
  申请人：Dana Farber Cancer Institute, Inc.

  公开号：EP3828185A2

  公开（公告）日：2021-06-02

  The present invention relates to novel pyrimido-diazepinone compounds, methods of modulating protein kinases, including MPS1 (TTK), ERK5 (BMK1, MAPK7), polo kinase 1,2,3, or 4, Ackl, Ack2, Abl, DCAMKL1, ABL1, Abl mutants, DCAMKL2, ARK5, BRK, MKNK2, FGFR4, TNK1, PLK1, ULK2, PLK4, PRKD1, PRKD2, PRKD3, ROS1, RPS6KA6, TAOK1, TAOK3, TNK2, Bcr-Abl, GAK, cSrc, TPR-Met, Tie2, MET, FGFR3, Aurora, Axl, Bmx, BTK, c-kit, CHK2, Flt3, MST2, p70S6K, PDGFR, PKB, PKC, Raf, ROCK-H, Rskl, SGK, TrkA, TrkB and TrkC, and the use of such compounds in the treatment of various diseases, disorders or conditions.

  本发明涉及新型嘧啶类二氮杂卓酮化合物、调节蛋白激酶的方法，包括MPS1（TTK）、ERK5（BMK1、MAPK7）、polo 激酶 1、2、3 或 4、Ackl、Ack2、Abl、DCAMKL1、ABL1、Abl 突变体、DCAMKL2、ARK5、BRK、MKNK2、FGFR4、TNK1、PLK1、ULK2、PLK4、PRKD1、PRKD2、PRKD3, ROS1, RPS6KA6, TAOK1, TAOK3, TNK2, Bcr-Abl, GAK, cSrc, TPR-Met, Tie2, MET, FGFR3, Aurora, Axl, Bmx, BTK, c-kit, CHK2, Flt3, MST2, p70S6K, PDGFR、PKB、PKC、Raf、ROCK-H、Rskl、SGK、TrkA、TrkB 和 TrkC。
• Inhibitors of ACK1/TNK2 tyrosine kinase
  申请人：H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

  公开号：US10017478B2

  公开（公告）日：2018-07-10

  Described are cancer therapies and anti-cancer compounds. In particular, disclosed are inhibitors of Ack1 tyrosine kinase and their use in the treatment of cancer. Methods of screening for new Ack1 tyrosine kinase inhibitors are also disclosed. In specific example, compound having Formula I through IV are disclosed.

  所述的是癌症疗法和抗癌化合物。 特别是公开了 Ack1 酪氨酸激酶的抑制剂及其在治疗癌症中的用途。 还公开了筛选新的Ack1酪氨酸激酶抑制剂的方法。 在具体实例中，公开了具有式I至式IV的化合物。