2-((2-methoxy-4-(piperazin-1-yl)phenyl)amino)-5,11-dimethyl-5,11-dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one | 1234481-27-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-((2-methoxy-4-(piperazin-1-yl)phenyl)amino)-5,11-dimethyl-5,11-dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one
• 英文别名: 2-(2-Methoxy-4-piperazin-1-ylanilino)-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one
• CAS: 1234481-27-6
• 化学式: C₂₄H₂₇N₇O₂
• 分子量: 445.524
• InChiKey: HGHFBVBNHYJNHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 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

• 作为反应物：
  描述：

  2-((2-methoxy-4-(piperazin-1-yl)phenyl)amino)-5,11-dimethyl-5,11-dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one 在 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 14.0h， 生成 2-(4-(4-((5,11-dimethyl-6-oxo-6,11-dihydro-5H-benzo[e]pyrimido[5,4-b][1,4]diazepin-2-yl)amino)-3-methoxyphenyl)piperazin-1-yl)acetic acid
  参考文献：
  名称：

  [EN] ERK5 DEGRADERS AS THERAPEUTICS IN CANCER AND INFLAMMATORY DISEASES
  [FR] AGENTS DE DÉGRADATION DE L'ERK5 UTILISÉS COMME AGENTS THÉRAPEUTIQUES DANS LE CANCER ET LES MALADIES INFLAMMATOIRES

  摘要：

  揭示了一种针对ERK5进行降解的双特异性化合物（降解剂）。还揭示了含有这些降解剂的药物组合物，以及使用这些化合物治疗癌症和炎症性疾病的方法。

  公开号：

  WO2021061894A1

文献信息

• 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。
• Design, Synthesis, and Biological Evaluation of Proteolysis-Targeting Chimeras as Highly Selective and Efficient Degraders of Extracellular Signal-Regulated Kinase 5
  作者：Pengming Pan、Tongtong Geng、Zhongtang Li、Xuyang Ding、Mengyuan Shi、Yang Li、Yashuai Wang、Yuanyuan Shi、Jiaojiao Wu、Liang Zhong、Dengbo Ji、Zhongjun Li、Xiangbao Meng

  DOI：10.1021/acs.jmedchem.3c00864

  日期：2023.10.12

  ERK5 inhibition in multiple studies are controversial, and a highly specific ERK5-targeting agent is required to confirm physiological functions. Using proteolysis-targeting chimera technology, we designed the selective ERK5 degrader PPM-3 and examined its biological effect on cancer cells. Interestingly, the selective degradation of ERK5 with PPM-3 did not influence tumor cell growth directly. Based

  细胞外信号调节激酶 5 (ERK5) 被认为是丝裂原激活蛋白激酶家族的关键成员，参与肿瘤生长、迁移和血管生成。然而，多项研究中ERK5抑制的结果存在争议，需要高度特异性的ERK5靶向剂来确认生理功能。利用蛋白水解靶向嵌合体技术，我们设计了选择性ERK5降解剂PPM-3，并检测了其对癌细胞的生物学效应。有趣的是， PPM-3选择性降解ERK5并不会直接影响肿瘤细胞的生长。根据蛋白质组学分析，ERK5缺失可能与肿瘤免疫相关。PPM-3通过影响巨噬细胞的分化来影响肿瘤的发展。因此，PPM-3是研究ERK5的有效小分子工具，也是一种有前途的免疫治疗候选药物。
• Pyrimido-diazepinone compounds and methods of treating disorders
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US10189861B2

  公开（公告）日：2019-01-29

  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）、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，以及将这些化合物用于治疗各种疾病、失调或病症。
• Pyrimido-diazepinone kinase scaffold compounds and methods of treating disorders
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US10570154B2

  公开（公告）日：2020-02-25

  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, 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、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。
• PYRIMIDO-DIAZEPINONE KINASE SCAFFOLD COMPOUNDS AND METHODS OF TREATING DISORDERS
  申请人：Gray Nathanael S.

  公开号：US20120040961A1

  公开（公告）日：2012-02-16

  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, Ack1, Ack2, AbI, DCAMKL1, ABL1, AbI mutants, DCAMKL2, ARK5, BRK, MKNK2, FGFR4, TNK1, PLK1, ULK2, PLK4, PRKD1, PRKD2, PRKD3, ROS 1, RPS6KA6, TAOK1, TAOK3, TNK2, Bcr-Abl, GAK, cSrc, TPR-Met, Tie2, MET, FGFR3, Aurora, AxI, 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.