MRT00033659 | 1401731-54-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: MRT00033659
• 英文别名: N-(3-(3-methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)phenyl)acetamide；N-[3-(3-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)phenyl]acetamide
• CAS: 1401731-54-1
• 化学式: C₁₅H₁₄N₄O
• 分子量: 266.302
• InChiKey: YFBPGSDPFRCNOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  70.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-溴-2-氯烟酸 在 Pd(dppt)Cl₂ 、 sodium carbonate 、 N,N'-羰基二咪唑 、 肼 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 MRT00033659
  参考文献：
  名称：

  A Casein kinase 1/Checkpoint kinase 1 pyrazolo-pyridine protein kinase inhibitor as novel activator of the p53 pathway

  摘要：

  Reactivation of the wild-type p53 pathway is one key goal aimed at developing targeted therapeutics in the cancer research field. Although most p53 protein kinases form 'p53-activating' signals, there are few kinases whose action can contribute to the inhibition of p53, as Casein kinase 1 (CK1) and Checkpoint kinase 1 (CHK1). Here we report on a pyrazolo-pyridine analogue showing activity against both CK1 and CHK1 kinases that lead to p53 pathway stabilisation, thus having pharmacological similarities to the p53-activator Nutlin-3. These data demonstrate the emerging potential utility of multivalent kinase inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.046

文献信息

• SUBSTITUTED 5-(PYRAZIN-2-YL)-1H-PYRAZOLO [3, 4-B] PYRIDINE AND PYRAZOLO [3, 4-B] PYRIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS
  申请人：Vankayalapati Hariprasad

  公开号：US20140309211A1

  公开（公告）日：2014-10-16

  Substituted 5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine, 5-(pyrazin-2-yl)-1H-pyrrolo[2,3-b]pyridine and pyrazolo[3,4-b]pyridine derivatives according to formula I, II and VII, and methods for making same, which are inhibitors of constitutively activated Tyrosine Kinase-Like (TKL), CMGC protein kinases family members and can be useful in the treatment of Parkinson's disease, Alzheimer's disease, Down's Syndrome, Huntington's disease, other neurodegenerative and central nervous system disorders, cancer, metabolic disorders and inflammatory diseases. Also disclosed are pharmaceutical compositions including the compounds and methods of inhibiting wild type and/or mutated protein kinase activities of these families and the treatment of disorders associated therewith using compounds and pharmaceutical compositions including the compounds.

  本发明涉及按照公式I、II和VII替代的5-(吡嗪-2-基)-1H-吡唑并[3,4-b]吡啶、5-(吡嗪-2-基)-1H-吡咯并[2,3-b]吡啶和吡唑并[3,4-b]吡啶衍生物，以及制备它们的方法。这些衍生物是组成激活的酪氨酸激酶样（TKL）、CMGC蛋白激酶家族成员的抑制剂，可用于治疗帕金森病、阿尔茨海默病、唐氏综合症、亨廷顿病、其他神经退行性和中枢神经系统疾病、癌症、代谢性疾病和炎症性疾病。本发明还公开了包括这些化合物的制药组合物和抑制这些家族的野生型和/或突变蛋白激酶活性的方法，以及使用包括这些化合物的化合物和制药组合物治疗相关疾病的方法。
• Substituted 5-(pyrazin-2-yl)-1H-pyrazolo [3, 4-B] pyridine and pyrazolo [3, 4-B] pyridine derivatives as protein kinase inhibitors
  申请人：Vankayalapati Hariprasad

  公开号：US08791112B2

  公开（公告）日：2014-07-29

  Substituted 5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine, 5-(pyrazin-2-yl)-1H-pyrrolo[2,3-b]pyridine and pyrazolo[3,4-b]pyridine derivatives according to formula I, II and VII, and methods for making same, which are inhibitors of constitutively activated Tyrosine Kinase-Like (TKL), CMGC protein kinases family members and can be useful in the treatment of Parkinson's disease, Alzheimer's disease, Down's Syndrome, Huntington's disease, other neurodegenerative and central nervous system disorders, cancer, metabolic disorders and inflammatory diseases. Also disclosed are pharmaceutical compositions including the compounds and methods of inhibiting wild type and/or mutated protein kinase activities of these families and the treatment of disorders associated therewith using compounds and pharmaceutical compositions including the compounds.

  本发明涉及根据式I，II和VII制备的5-（吡嗪-2-基）-1H-吡唑并[3,4-b]吡啶，5-（吡嗪-2-基）-1H-吡咯并[2,3-b]吡啶和吡唑并[3,4-b]吡啶衍生物，以及制备它们的方法，这些衍生物是构成性激活的酪氨酸激酶样（TKL）CMGC蛋白激酶家族成员的抑制剂，可用于治疗帕金森病、阿尔茨海默病、唐氏综合症、亨廷顿病、其他神经退行性和中枢神经系统疾病、癌症、代谢性疾病和炎症性疾病。本发明还公开了包括这些化合物的药物组合物和抑制这些家族的野生型和/或突变蛋白激酶活性的方法以及使用包括这些化合物的化合物和药物组合物治疗相关疾病的方法。
• Substituted 5-(pyrazin-2-yl)-1H-pyrazolo [3, 4-b] pyridine and pyrazolo [3, 4-b] pyridine derivatives as protein kinase inhibitors
  申请人：Arrien Pharmaceuticals LLC

  公开号：US09187473B2

  公开（公告）日：2015-11-17

  Substituted 5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine, 5-(pyrazin-2-yl)-1H-pyrrolo[2,3-b]pyridine and pyrazolo[3,4-b]pyridine derivatives according to formula I, II and VII, and methods for making same, which are inhibitors of constitutively activated Tyrosine Kinase-Like (TKL), CMGC protein kinases family members and can be useful in the treatment of Parkinson's disease, Alzheimer's disease, Down's Syndrome, Huntington's disease, other neurodegenerative and central nervous system disorders, cancer, metabolic disorders and inflammatory diseases. Also disclosed are pharmaceutical compositions including the compounds and methods of inhibiting wild type and/or mutated protein kinase activities of these families and the treatment of disorders associated therewith using compounds and pharmaceutical compositions including the compounds.

  本发明提供了根据式I、II和VII制备的5-(吡嗪-2-基)-1H-吡唑并[3,4-b]吡啶、5-(吡嗪-2-基)-1H-吡咯并[2,3-b]吡啶和吡唑并[3,4-b]吡啶衍生物的替代物，以及制备这些替代物的方法。这些替代物是组成激活的酪氨酸激酶样（TKL）CMGC蛋白激酶家族成员的抑制剂，可用于治疗帕金森病、阿尔茨海默病、唐氏综合症、亨廷顿病、其他神经退行性和中枢神经系统疾病、癌症、代谢性疾病和炎症性疾病。本发明还揭示了包括这些化合物的药物组合物和通过使用这些化合物和药物组合物来抑制这些家族的野生型和/或突变蛋白激酶活性的方法以及使用这些化合物和药物组合物来治疗与其相关的疾病的方法。
• [EN] SUBSTITUTED 5-(PYRAZIN-2-YL)-1H-PYRAZOLO [3, 4-B] PYRIDINE AND PYRAZOLO [3, 4-B] PYRIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS<br/>[FR] 5-(PYRAZIN-2-YL)-1H-PYRAZOLO[3,4-B]PYRIDINE SUBSTITUÉE ET DÉRIVÉS DE PYRAZOLO[3,4-B]PYRIDINE EN TANT QU'INHIBITEURS DE PROTÉINE KINASE
  申请人：ARRIEN PHARMACEUTICALS LLC

  公开号：WO2012135631A8

  公开（公告）日：2012-12-06
• US8791112B2
  申请人：——

  公开号：US8791112B2

  公开（公告）日：2014-07-29