[4-(4-pyridyloxy)phenyl]boronic acid | 1029438-35-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [4-(4-pyridyloxy)phenyl]boronic acid
• 英文别名: 4-(Pyridin-4-yloxy)phenylboronic acid；(4-pyridin-4-yloxyphenyl)boronic acid
• CAS: 1029438-35-4
• 化学式: C₁₁H₁₀BNO₃
• 分子量: 215.016
• InChiKey: FZJIYBQVWBTPCY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.55
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  62.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [4-(4-pyridyloxy)phenyl]boronic acid 、 6-bromo-8-chloro-N-propylisoquinolone 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 8-Chloro-2-propyl-6-(4-pyridin-4-yloxyphenyl)isoquinolin-1-one
  参考文献：
  名称：

  New positive allosteric modulators of the metabotropic glutamate receptor 2 (mGluR2): Identification and synthesis of N-propyl-8-chloro-6-substituted isoquinolones

  摘要：

  A series of N-propyl-8-chloro-6-substituted isoquinolones was identified as positive allosteric modulators of metabotropic glutamate receptor 2 (mGluR2 PAM) via high throughput screening (HTS). The subsequent synthesis and initial SAR exploration that led to the identification of compound 28 is described. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.048

文献信息

• Discovery of Evobrutinib: An Oral, Potent, and Highly Selective, Covalent Bruton’s Tyrosine Kinase (BTK) Inhibitor for the Treatment of Immunological Diseases
  作者：Richard D. Caldwell、Hui Qiu、Ben C. Askew、Andrew T. Bender、Nadia Brugger、Montserrat Camps、Mohanraj Dhanabal、Vikram Dutt、Thomas Eichhorn、Anna S. Gardberg、Andreas Goutopoulos、Roland Grenningloh、Jared Head、Brian Healey、Brian L. Hodous、Bayard R. Huck、Theresa L. Johnson、Christopher Jones、Reinaldo C. Jones、Igor Mochalkin、Federica Morandi、Ngan Nguyen、Michael Meyring、Justin R. Potnick、Dusica Cvetinovic Santos、Ralf Schmidt、Brian Sherer、Adam Shutes、Klaus Urbahns、Ariele Viacava Follis、Ansgar A. Wegener、Simone C. Zimmerli、Lesley Liu-Bujalski

  DOI：10.1021/acs.jmedchem.9b00794

  日期：2019.9.12

  Bruton's tyrosine kinase (BTK) inhibitors such as ibrutinib hold a prominent role in the treatment of B cell malignancies. However, further refinement is needed to this class of agents, particularly in terms of adverse events (potentially driven by kinase promiscuity), which preclude their evaluation in nononcology indications. Here, we report the discovery and preclinical characterization of evobrutinib

  Bruton的酪氨酸激酶（BTK）抑制剂如ibrutinib在B细胞恶性肿瘤的治疗中起着重要作用。但是，此类药物需要进一步改进，特别是在不良事件（可能由激酶混杂引起的不良事件）方面，这使其无法在非肿瘤适应症中进行评估。在这里，我们报告evobrutinib的发现和临床前表征，evobrutinib是一种具有高激酶选择性的有效的专性共价抑制剂。Evobrutinib表现出足够的临床前药代动力学和药效动力学特征，可在功效模型中进行体内评估。此外，依武鲁替尼对BTK的选择性高于表皮生长因子受体和其他Tec家族激酶，这表明脱靶相关不良反应的可能性较低。
• Compositions and Methods for the Production of Pyrimidine and Pyridine Compounds with BTK Inhibitory Activity
  申请人：Hodous Brian L.

  公开号：US20140162983A1

  公开（公告）日：2014-06-12

  The present invention provides novel pyrimidine and pyridine compounds according to Formula (I), Formula (II), Formula (III), Formula (IV) and Formula (V) their manufacture and use for the treatment of hyperproliferative diseases including, but not limited to, cancer, lupus, allergic disorders, Sjogren's disease and rheumatoid arthritis. In preferred embodiments, the present invention describes irreversible kinase inhibitors including, but not limited to, inhibitors of Bruton's tyrosine kinase.

  本发明提供了新型嘧啶和吡啶化合物，其符合公式（I），公式（II），公式（III），公式（IV）和公式（V），以及它们的制备和用于治疗高增殖性疾病，包括但不限于癌症，狼疮，过敏性疾病，Sjogren's病和类风湿性关节炎。在优选实施例中，本发明描述了不可逆激酶抑制剂，包括但不限于布鲁顿酪氨酸激酶抑制剂。
• Compositions and methods for the production of pyrimidine and pyridine compounds with BTK inhibitory activity
  申请人：Hodous Brian L.

  公开号：US09073947B2

  公开（公告）日：2015-07-07

  The present invention provides novel pyrimidine and pyridine compounds according to Formula (I), Formula (II), Formula (III), Formula (IV) and Formula (V) their manufacture and use for the treatment of hyperproliferative diseases including, but not limited to, cancer, lupus, allergic disorders, Sjogren's disease and rheumatoid arthritis. In preferred embodiments, the present invention describes irreversible kinase inhibitors including, but not limited to, inhibitors of Bruton's tyrosine kinase.

  本发明提供了根据公式(I)、公式(II)、公式(III)、公式(IV)和公式(V)的新型嘧啶和吡啶化合物，它们的制造和用于治疗包括但不限于癌症、狼疮、过敏性疾病、Sjogren综合症和类风湿性关节炎等增殖性疾病。在优选实施例中，本发明描述了不可逆激酶抑制剂，包括但不限于布鲁顿酪氨酸激酶抑制剂。
• COMPOSITIONS AND METHODS FOR THE PRODUCTION OF PYRIMIDINE AND PYRIDINE COMPOUNDS WITH BTK INHIBITORY ACTIVITY
  申请人：Merck Patent GmbH

  公开号：US20150259363A1

  公开（公告）日：2015-09-17

  The present invention provides novel pyrimidine and pyridine compounds according to Formula (I), Formula (II), Formula (III), Formula (IV) and Formula (V) their manufacture and use for the treatment of hyperproliferative diseases including, but not limited to, cancer, lupus, allergic disorders, Sjogren's disease and rheumatoid arthritis. In preferred embodiments, the present invention describes irreversible kinase inhibitors including, but not limited to, inhibitors of Bruton's tyrosine kinase.

  本发明提供了新的嘧啶和吡啶化合物，包括式(I)、式(II)、式(III)、式(IV)和式(V)，以及它们的制备和用于治疗高增殖性疾病，包括但不限于癌症、狼疮、过敏性疾病、干燥综合症和类风湿性关节炎。在优选实施例中，本发明描述了不可逆激酶抑制剂，包括但不限于布鲁顿酪氨酸激酶抑制剂。
• New positive allosteric modulators of the metabotropic glutamate receptor 2 (mGluR2): Identification and synthesis of N-propyl-8-chloro-6-substituted isoquinolones
  作者：Andrés A. Trabanco、Guillaume Duvey、José María Cid、Gregor J. Macdonald、Philippe Cluzeau、Vanthea Nhem、Rocco Furnari、Nadia Behaj、Géraldine Poulain、Terry Finn、Hilde Lavreysen、Sonia Poli、Alexandre Raux、Yves Thollon、Nicolas Poirier、David D’Addona、José Ignacio Andrés、Robert Lutjens、Emmanuel Le Poul、Hassan Imogai、Jean-Philippe Rocher

  DOI：10.1016/j.bmcl.2010.12.048

  日期：2011.2

  A series of N-propyl-8-chloro-6-substituted isoquinolones was identified as positive allosteric modulators of metabotropic glutamate receptor 2 (mGluR2 PAM) via high throughput screening (HTS). The subsequent synthesis and initial SAR exploration that led to the identification of compound 28 is described. (C) 2010 Elsevier Ltd. All rights reserved.