1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole-3-carbaldehyde | 850892-14-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole-3-carbaldehyde
• 英文别名: 1-(tetrahydro-pyran-2-yl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indazole-3-carbaldehyde；1-(oxan-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indazole-3-carbaldehyde
• CAS: 850892-14-7
• 化学式: C₁₉H₂₅BN₂O₄
• 分子量: 356.229
• InChiKey: DTMUGJQIZZUQCF-UHFFFAOYSA-N

物化性质

• 沸点：
  530.9±50.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.85
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  62.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole-3-carbaldehyde 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 碘 、 sodium carbonate 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  5-吡啶-1H-吲唑类化合物、药物组合物和应用

  摘要：

  本发明公开了一种5‑吡啶‑1H‑吲唑类化合物、药物组合物和应用。该化合物结构如式I或II，其还包含其异构体、药学上可接受的盐或它们的混合物。该类化合物及其药物组合物可有效抑制CLK2蛋白及DYRK1A蛋白活性，可制备为治疗骨关节炎的药物，在分子水平可以发挥药效，并且治疗效果更优异，最优可达到纳摩尔浓度水平。此外，化合物制备方法简便、易操作。

  公开号：

  CN115353508A
• 作为产物：
  描述：

  5-溴吲唑-3-甲醛 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 14.0h， 生成 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole-3-carbaldehyde
  参考文献：
  名称：

  [EN] FUSED RING COMPOUND, AND INTERMEDIATE THEREOF, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
  [FR] COMPOSÉ À CYCLES FUSIONNÉS, ET INTERMÉDIAIRE DE CELUI-CI, PROCÉDÉ DE PRÉPARATION ASSOCIÉ ET APPLICATION
  [ZH] 稠环化合物及其中间体、制备方法和应用

  摘要：

  提供了一种如式Ia或Ib所示的化合物、其药学上可接受的盐、其水合物、其溶剂化物、其多晶型、其代谢产物、其立体异构体、其互变异构体或其前药。该化合物作为Wnt抑制剂以及间充质干细胞诱导剂，对sox9、Ⅰ型胶原、Ⅹ型胶原、成骨转录基因和碱性磷酸酶中的一种或多种具有较好的诱导作用，进而可以用来制备治疗和/或改善相关的疾病和病症的药物。

  公开号：

  WO2022012058A1

文献信息

• 3,5 Disubstituted indazole compounds with nitrogen-bearing 5-membered heterocycles, pharmaceutical compositions, and methods for mediating or inhibiting cell proliferation
  申请人：McAlpine James Indrawan

  公开号：US20050090529A1

  公开（公告）日：2005-04-28

  3,5 disubstituted indazole compounds with substituted nitrogen bearing 5-membered heterocycles in the 3-position that modulate and/or inhibit cell proliferation, such as the activity of protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating CDK dependent diseases to modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating cancer as well as other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.

  描述了在3-位置带有取代氮的5-成员杂环的3,5-二取代吲唑化合物，这些化合物调节和/或抑制细胞增殖，如蛋白激酶活性。这些化合物和含有它们的药物组合物能够调节和/或抑制介导CDK依赖性疾病的不需要的细胞增殖。该发明还涉及含有这些化合物的药物组合物的治疗或预防用途，以及通过给予这些化合物的有效量来治疗癌症以及与不需要的血管生成和/或细胞增殖相关的其他疾病状态，如糖尿病视网膜病变、新生血管性青光眼、类风湿性关节炎和牛皮癣的方法。
• [EN] INDAZOLE-3-CARBOXAMIDES AND THEIR USE AS WNT/B-CATENIN SIGNALING PATHWAY INHIBITORS<br/>[FR] INDAZOLE-3-CARBOXAMIDES ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE LA VOIE DE SIGNALISATION PAR WNT/Beta-CATÉNINE
  申请人：SAMUMED LLC

  公开号：WO2013040215A1

  公开（公告）日：2013-03-21

  lndazole-3-carboxamide compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an indazole-3- carboxamide compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

  本文披露了用于治疗各种疾病和病理的吲唑-3-羧酰胺化合物。更具体地，本文涉及使用吲唑-3-羧酰胺化合物或其类似物治疗由Wnt途径信号激活所特征的疾病（例如癌症、异常细胞增殖、血管生成和骨关节炎），调节由Wnt途径信号介导的细胞事件，以及由于Wnt途径和/或Wnt信号组分之一或多个的突变或失调而引起的遗传疾病和神经系统疾病/紊乱/疾病。还提供了治疗与Wnt相关疾病状态的方法。
• [EN] METHODS OF USING INDAZOLE-3-CARBOXAMIDES AND THEIR USE AS WNT/B-CATENIN SIGNALING PATHWAY INHIBITORS<br/>[FR] PROCÉDÉS D'UTILISATION D'INDAZOLE-3-CARBOXAMIDES ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE LA VOIE DE SIGNALISATION WNT/β-CATÉNINE
  申请人：SAMUMED LLC

  公开号：WO2018075858A1

  公开（公告）日：2018-04-26

  This disclosure features the use of one or more indazole-3-carboxamide compounds or salts or analogs thereof, in the treatment of one or more diseases or conditions independently selected from the group consisting of a tendinopathy, dermatitis, psoriasis, morphea, ichthyosis, Raynaud's syndrome, and Darier's disease; and/or for promoting wound healing. The methods include administering to a subject (e.g., a subject in need thereof) a therapeutically effective amount of one or more indazole-3-carboxamide compounds or salts or analogs thereof as described anywhere herein.

  本公开涉及使用一种或多种吲唑-3-羧酰胺化合物或其盐或类似物，用于治疗独立选择自包括肌腱病、皮炎、牛皮癣、硬皮病、鱼鳞病、雷诺综合征和达里尔病的一种或多种疾病或症状；和/或促进伤口愈合。方法包括向受试者（例如，需要者）施用如本文中任何地方所述的一种或多种吲唑-3-羧酰胺化合物或其盐或类似物的治疗有效量。
• INDAZOLE INHIBITORS OF THE WNT SIGNAL PATHWAY AND THERAPEUTIC USES THEREOF
  申请人：SAMUMED, LLC

  公开号：US20130267495A1

  公开（公告）日：2013-10-10

  Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

  揭示了用于治疗各种疾病和病理的吲唑化合物。更具体地，本发明涉及使用吲唑化合物或其类似物治疗由Wnt途径信号激活所特征化的疾病（例如癌症、异常细胞增殖、血管生成、阿尔茨海默病、肺病和骨关节炎）、调节由Wnt途径信号介导的细胞事件，以及由于Wnt途径和/或一个或多个Wnt信号组分的突变或失调而引起的遗传疾病和神经系统疾病/疾患。还提供了治疗与Wnt相关疾病状态的方法。
• Discovery of indazoles as inhibitors of Tpl2 kinase
  作者：Yonghan Hu、Derek Cole、Rajiah Aldrin Denny、David R. Anderson、Manus Ipek、Yike Ni、Xiaolun Wang、Suvit Thaisrivongs、Timothy Chamberlain、J. Perry Hall、Julie Liu、Michael Luong、Lih-Ling Lin、Jean-Baptiste Telliez、Ariamala Gopalsamy

  DOI：10.1016/j.bmcl.2011.06.065

  日期：2011.8

  Synthesis, modeling and structure-activity relationship of indazoles as inhibitors of Tpl2 kinase are described. From a high throughput screening effort, we identified an indazole hit compound 5 that has a single digit micromolar Tpl2 activity. Through SAR modifications at the C3 and C5 positions of the indazole, we discovered compound 31 with good potency in LANCE assay and cell-based p-Erk assay. (C) 2011 Elsevier Ltd. All rights reserved.