4-((4-甲基哌嗪-1-基)甲基)苯硼酸 | 763120-62-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-((4-甲基哌嗪-1-基)甲基)苯硼酸
• 中文别名: 4-((4-乙基哌嗪-1-基)甲基)苯基硼酸
• 英文名称: (4-((4-methylpiperazin-1-yl)methyl)phenyl)boronic acid
• 英文别名: 4-((4-Methylpiperazin-1-yl)methyl)phenylboronic acid；[4-[(4-methylpiperazin-1-yl)methyl]phenyl]boronic acid
• CAS: 763120-62-3
• 化学式: C₁₂H₁₉BN₂O₂
• 分子量: 234.106
• InChiKey: JWRMKWKJAQFZKF-UHFFFAOYSA-N

物化性质

• 沸点：
  389.1±52.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.89
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  46.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-((4-甲基哌嗪-1-基)甲基)苯硼酸 在 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成
  参考文献：
  名称：

  Discovery of (E)-N¹-(3-Fluorophenyl)-N³-(3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)malonamide (CHMFL-KIT-033) as a Novel c-KIT T670I Mutant Selective Kinase Inhibitor for Gastrointestinal Stromal Tumors (GISTs)

  摘要：

  Gain-of-function mutations of c-KIT kinase play crucial pathological roles for the gastrointestinal stromal tumors (GISTs). Despite the success of imatinib as the first line treatment of GISTs, dozens of drug-acquired resistant mutations emerge, and c-KIT T670I is one of the most common mutants among them. Although several kinase inhibitors are capable of overcoming the T670I mutant, none of them can achieve the selectivity over the c-KIT wild-type (wt), which also plays important roles in a variety of physiological functions such as hematopoiesis. Starting from axitinib, through fragment hybrid type II kinase inhibitor design approach, we have discovered a novel inhibitor 24, which not only exhibits potent activity to c-KIT T670I mutant but also achieves 12-fold selectivity over c-KIT wt. Compound 24 displays good antiproliferative effects against c-KIT T670I mutant driven GIST cell lines (GIST-T1/T670I and GIST-5R) and also exhibits suitable in vivo pharmacokinetic profiles as well as dose-dependent antitumor efficacy. This study provides a proof of concept for developing a c-KIT mutant selective inhibitor that theoretically can render a better therapeutic window.

  DOI：

  10.1021/acs.jmedchem.9b00176
• 作为产物：
  描述：

  1-[(4-溴苯基)甲基]-4-甲基哌嗪 在 正丁基锂 、 硼酸三异丙酯 作用下， 以 四氢呋喃 为溶剂， 以67.3%的产率得到4-((4-甲基哌嗪-1-基)甲基)苯硼酸
  参考文献：
  名称：

  [EN] PEPTIDYL NITRIL COMPOUNDS AS DIPEPTIDYL PEPTIDASE I INHIBITORS
  [FR] COMPOSÉS PEPTIDYLNITRILE EN TANT QU'INHIBITEURS DE LA DIPEPTIDYLE PEPTIDASE I

  摘要：

  该发明涉及式（I）化合物及其作为选择性二肽基肽酶I抑制剂的用途，以及包含该化合物的药物组合物，以及涉及该化合物的治疗方法。

  公开号：

  WO2015032943A1
• 作为试剂：
  描述：

  5-bromo-7-(trans-4-((tertbutyldimethylsilyl)oxy)cyclohexyl)-N-(2-cyclopropylethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine 、 4-((4-甲基哌嗪-1-基)甲基)苯硼酸 在 4-((4-甲基哌嗪-1-基)甲基)苯硼酸 作用下， 生成
  参考文献：
  名称：

  Pyrrolopyrimidine compounds for the treatment of cancer

  摘要：

  Mer受体酪氨酸激酶（Mer）的异位表达已被确认为急性淋巴细胞白血病（ALL）细胞的肿瘤细胞存活基因产物和ALL化疗耐药的潜在原因。因此，我们调查了是否可能开发小分子Mer抑制剂。本发明的第一个方面是公式I，IA或IB的化合物（以下有时称为“活性化合物”）。

  公开号：

  US09273056B2

文献信息

• Aryl- or Heteroaryl-Substituted Benzene Compounds
  申请人：KUNTZ KEVIN W.

  公开号：US20120264734A1

  公开（公告）日：2012-10-18

  The present invention relates to aryl- or heteroaryl-substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.

  本发明涉及芳基或杂芳基取代的苯化合物。本发明还涉及含有这些化合物的药物组合物，以及通过向需要的受试者投与这些化合物和药物组合物来治疗癌症的方法。本发明还涉及利用这些化合物进行研究或其他非治疗目的的用途。
• [EN] HETEROARYL COMPOUNDS AND THEIR USE AS THERAPEUTIC DRUGS<br/>[FR] COMPOSÉS HÉTÉROARYLE ET LEUR UTILISATION COMME MÉDICAMENTS THÉRAPEUTIQUES
  申请人：DONG-A SOCIO HOLDINGS CO LTD

  公开号：WO2017039331A1

  公开（公告）日：2017-03-09

  The present invention provides heterocyclic compounds, the stereoisomer thereof, the enantiomer thereof, or the pharmaceutically acceptable salt, which are capable of modulating the activity of Mer receptor tyrosine kinase (MERTK). This invention also provides pharmaceutical compositions thereof, methods to prepare the said compounds, and the use of such compounds as a medicament. The present invention is directed to MERTK inhibitory compounds with marked potency, thereby having an outstanding potential for a pharmaceutical intervention of cancer and any other diseases related to MERTK dysregulation.

  本发明提供了一种杂环化合物、其立体异构体、对映异构体或药用可接受的盐，这些化合物能够调节Mer受体酪氨酸激酶（MERTK）的活性。本发明还提供了这些化合物的药物组合物、制备所述化合物的方法以及将这些化合物用作药物的应用。本发明针对的是具有显著活性的MERTK抑制性化合物，因此具有在癌症和任何与MERTK调控失调相关的疾病中进行药物干预的卓越潜力。
• [EN] PYRIMIDINES AS KINASE INHIBITORS<br/>[FR] PYRIMIDINES UTILISÉS EN TANT QU'INHIBITEURS DE KINASE
  申请人：NOVARTIS AG

  公开号：WO2009087224A1

  公开（公告）日：2009-07-16

  Compounds of formula (I) in free or salt or solvate form, where T1, T2, and T3 have the meanings as indicated in the specification, are useful for treating inflammatory or obstructive airways, pulmonary hypertension, pulmonary fibrosis, liver fibrosis, muscle diseases and systemic skeletal disorders. Pharmaceutical compositions that contain the compounds and processes for preparing the compounds are also described.

  式（I）的化合物以自由形式、盐形式或溶剂合物形式存在，其中T1、T2和T3的含义如规范中所示，可用于治疗炎症性或阻塞性气道、肺动脉高压、肺纤维化、肝纤维化、肌肉疾病和全身骨骼疾病。还描述了含有这些化合物的药物组合物和制备这些化合物的方法。
• [EN] 7-AZAINDOLE DERIVATIVES AS PARP INHIBITORS<br/>[FR] DÉRIVÉS DE 7-AZAINDOLE UTILISÉS EN TANT QU'INHIBITEURS DE PARP
  申请人：SIGMA TAU IND FARMACEUTI

  公开号：WO2015011008A1

  公开（公告）日：2015-01-29

  The present invention relates to 7-azaindole derivatives of Formula (I), pharmaceutical compositions containing such derivatives. The invention further relates to said pharmaceutical compositions for use in medicine, and more particularly in the treatment of cancer diseases where an inhibition of PARP is responsive.

  本发明涉及公式（I）的7-氮杂吲哚衍生物，包含这种衍生物的药物组合物。该发明进一步涉及用于医学用途的上述药物组合物，更具体地用于治疗癌症疾病，其中对PARP的抑制是有效的。
• [EN] MIXED LINEAGE KINASE INHIBITORS FOR HIV/AIDS THERAPIES<br/>[FR] INHIBITEURS DE KINASE DE LIGNAGE MIXTE POUR DES THÉRAPIES POUR LE VIH/SIDA
  申请人：UNIV ROCHESTER

  公开号：WO2014085795A1

  公开（公告）日：2014-06-05

  Disclosed are methods for treating an individual infected with a retrovirus that comprise administering to the individual effective amounts of a mixed lineage kinase inhibitor and antiretroviral drug. In further aspects, disclosed are methods for treating an individual infected with a retrovirus that comprises administering an antiretroviral drug formulated into a crystalline nanoparticle comprising a surfactant, and a MLK inhibitor. Still further disclosed are methods for treating an individual infected with a retrovirus that comprises administering a composition comprising both an antiretroviral and MLK inhibitor formulated into a crystalline nanoparticle, which comprises a surfactant. Still further disclosed are compositions that comprise an antiretroviral drug, a MLK inhibitor, and a surfactant, wherein the composition is a crystalline nanoparticle. Compostions comprising MLK inhibitors with other drugs in nanoparticulate form, and methods of there use, are also disclosed.

  揭示了治疗感染逆转录病毒的个体的方法，包括向个体施用有效量的混合谱系激酶抑制剂和抗逆转录病毒药物。此外，还揭示了治疗感染逆转录病毒的个体的方法，包括向个体施用配制成含有表面活性剂的结晶纳米粒子的抗逆转录病毒药物，以及MLK抑制剂。进一步揭示了治疗感染逆转录病毒的个体的方法，包括向个体施用包含抗逆转录病毒和MLK抑制剂的组合物，该组合物配制成含有表面活性剂的结晶纳米粒子。还揭示了包含抗逆转录病毒药物、MLK抑制剂和表面活性剂的组合物，其中该组合物是结晶纳米粒子。还揭示了包含MLK抑制剂与其他药物在纳米粒形式中的组合物，以及其使用方法。