(4-(3-bromoimidazo[1,2-a]pyrazin-6-yl)phenyl)(4-methylpiperazin-1-yl)methanone | 1464153-42-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4-(3-bromoimidazo[1,2-a]pyrazin-6-yl)phenyl)(4-methylpiperazin-1-yl)methanone
• 英文别名: (4-(3-Bromoimidazo[1,2-a]pyrazin-6-yl)phenyl)(4-methylpiperazin-1-yl)methanone；[4-(3-bromoimidazo[1,2-a]pyrazin-6-yl)phenyl]-(4-methylpiperazin-1-yl)methanone
• CAS: 1464153-42-1
• 化学式: C₁₈H₁₈BrN₅O
• 分子量: 400.278
• InChiKey: KPYYYOWALKJQSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  53.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-(3-bromoimidazo[1,2-a]pyrazin-6-yl)phenyl)(4-methylpiperazin-1-yl)methanone 在 盐酸 、 potassium phosphate 、 四(三苯基膦)钯 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 33.0h， 生成 N-hydroxy-4-(6-(4-(4-methylpiperazine-1-carbonyl)phenyl)imidazo[1,2-a]pyrazin-3-yl)benzamide
  参考文献：
  名称：

  [EN] BICYCLIC HETEROCYCLIC DERIVATIVES AS MNK1 AND MNK2 MODULATORS AND USES THEREOF
  [FR] DÉRIVÉS HÉTÉROCYCLIQUES BICYCLIQUES À TITRE DE MODULATEURS DE MNK1 ET MNK2 ET LEURS UTILISATIONS

  摘要：

  本发明涉及某些化合物（例如咪唑吡嗪、咪唑吡啶、咪唑吡嗪和咪唑嘧啶化合物），这些化合物作为MAP激酶相互作用激酶MNK2a、MNK2b、MNK1a和MNK1b的抑制剂。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物制备用于预防和治疗疾病（例如增生性疾病（例如癌症）、炎症性疾病、阿尔茨海默病）的药物的用途，以及治疗这些疾病的方法。

  公开号：

  WO2013147711A1
• 作为产物：
  描述：

  4-乙氧羰基苯硼酸 在 N-甲基吗啉 、 N-溴代丁二酰亚胺(NBS) 、 caesium carbonate 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 27.5h， 生成 (4-(3-bromoimidazo[1,2-a]pyrazin-6-yl)phenyl)(4-methylpiperazin-1-yl)methanone
  参考文献：
  名称：

  Optimization of Selective Mitogen-Activated Protein Kinase Interacting Kinases 1 and 2 Inhibitors for the Treatment of Blast Crisis Leukemia

  摘要：

  Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by bcr-abll, a constitutively active tyrosine kinase fusion gene responsible for an abnormal proliferation of leukemic stem cells (LSCs). Inhibition of BCR-ABL1 kinase activity offers long-term relief to CML patients. However, for a proportion of them, BCR-ABL1 inhibition will become ineffective at treating the disease, and CML will progress to blast crisis (BC) CML with poor prognosis. BC-CML is often associated with excessive phosphorylated eukaryotic translation initiation factor 4E (eIF4E), which renders LSCs capable of proliferating via self-renewal, oblivious to BCR-ABL1 inhibition. In vivo, eIF4E is exclusively phosphorylated on Ser209 by MNK1/2. Consequently, a selective inhibitor of MNK1/2 should reduce the level of phosphorylated eIF4E and re-sensitize LSCs to BCR-ABL1 inhibition, thus hindering the proliferation of BC LSCs. We report herein the structure activity relationships and pharmacokinetic properties of a selective MNK1/2 inhibitor clinical candidate, ETC-206, which in combination with dasatinib prevents BC-CML LSC self-renewal in vitro and enhances dasatinib antitumor activity in vivo.

  DOI：

  10.1021/acs.jmedchem.7b01714

文献信息

• BICYCLIC HETEROCYCLIC DERIVATIVES AS MNK1 AND MNK2 MODULATORS AND USES THEREOF
  申请人：Agency for Science, Technology and Research

  公开号：US20140371199A1

  公开（公告）日：2014-12-18

  The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.

  本发明涉及某些化合物（例如咪唑吡嗪、咪唑吡啶、咪唑吡嗪和咪唑嘧啶化合物），这些化合物作为MAP激酶相互作用激酶MNK2a、MNK2b、MNK1a和MNK1b的抑制剂。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物制备用于预防和治疗疾病（例如增生性疾病（例如癌症）、炎症性疾病、阿尔茨海默病）的药物的用途，以及治疗这些疾病的方法。
• BICYCLIC HETEROARYL DERIVATIVES AS MNK1 AND MNK2 MODULATORS AND USES THEREOF
  申请人：Agency for Science, Technology and Research

  公开号：US20150038506A1

  公开（公告）日：2015-02-05

  The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), neurodegenerative diseases (e.g., Alzheimer's disease), metabolic diseases (e.g. diabetes), neurodevelopmental disorders (e.g. autism), or psychiatric disorders (e.g. schizophrenia or anxiety)) as well as methods of treating these diseases.

  本发明涉及某些化合物（例如，咪唑吡嗪、咪唑吡啶、咪唑吡嗪和咪唑嘧啶化合物），它们作为MAP激酶相互作用激酶MNK2a、MNK2b、MNK1a和MNK1b的抑制剂。本发明还涉及包含这些化合物的药物组合物，以及使用这些化合物制备预防和治疗疾病（例如增生性疾病（例如癌症），神经退行性疾病（例如阿尔茨海默病），代谢性疾病（例如糖尿病），神经发育障碍（例如自闭症），或精神障碍（例如精神分裂症或焦虑症））的药物以及治疗这些疾病的方法。
• Bicyclic heteroaryl derivatives as MNK1 and MNK2 modulators and uses thereof
  申请人：Agency for Science, Technology and Research

  公开号：US10280168B2

  公开（公告）日：2019-05-07

  The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazopyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), neurodegenerative diseases (e.g., Alzheimer's disease), metabolic diseases (e.g. diabetes), neurodevelopmental disorders (e.g. autism), or psychiatric disorders (e.g. schizophrenia or anxiety)) as well as methods of treating these diseases.

  本发明涉及某些作为MAP激酶相互作用激酶MNK2a、MNK2b、MNK1a和MNK1b的抑制剂的化合物（例如咪唑吡嗪、咪唑吡啶、咪唑哒嗪和咪唑嘧啶化合物）。本发明进一步涉及包含这些化合物的药物组合物，以及这些化合物用于制备预防和治疗疾病（如增殖性疾病（如癌症）、神经退行性疾病（如阿尔茨海默病）、代谢性疾病（如糖尿病）、神经发育障碍（如自闭症）或精神障碍（如精神分裂症或焦虑症））的药物以及治疗这些疾病的方法。
• Bicyclic heterocyclic derivatives as MNK1 and MNK2 modulators and uses thereof
  申请人：Agency for Science, Technology, and Research

  公开号：US11040978B2

  公开（公告）日：2021-06-22

  The present invention relates to compounds of Formula (Ib-I) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.

  本发明涉及作为MAP激酶相互作用激酶MNK2a、MNK2b、MNK1a和MNK1b的抑制剂的式(Ib-I)化合物。本发明进一步涉及包含这些化合物的药物组合物，以及使用这些化合物制备预防和治疗疾病（如增殖性疾病（如癌症）、炎症性疾病、阿尔茨海默病）的药物，以及治疗这些疾病的方法。
• EP2831079B1
  申请人：——

  公开号：EP2831079B1

  公开（公告）日：2017-08-16