4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole | 1158680-92-2

• 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: 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole
• 英文别名: trimethyl-[2-[[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indazol-1-yl]methoxy]ethyl]silane
• CAS: 1158680-92-2
• 化学式: C₁₉H₃₁BN₂O₃Si
• 分子量: 374.363
• InChiKey: OODJUGQLBCMWMN-UHFFFAOYSA-N

物化性质

• 沸点：
  458.6±30.0 °C(Predicted)
• 密度：
  1.04±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.65
• 重原子数：
  26.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  45.51
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole 在 四(三苯基膦)钯 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 15.0h， 生成 tert-butyl 4-((5-cyano-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-4-yl)pyridin-2-yl)amino)piperidine-1-carboxylate
  参考文献：
  名称：

  CYCLIN-DEPENDENT KINASE 12 MODULATORS AND THERAPEUTIC USES THEREOF

  摘要：

  Provided herein are compounds having a structure of Formula (I) and pharmaceutically acceptable salts thereof which can act as modulators of cyclin-dependent kinase 12 (CDK12). Further disclosed herein are methods for treating cancer and cancer-related diseases and disorders, such as breast cancer, ovarian cancer, prostate cancer, and gastric cancer.

  公开号：

  WO2024148210A1
• 作为产物：
  描述：

  4-溴-1H-吲唑 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 sodium hydride 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.5h， 生成 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole
  参考文献：
  名称：

  CYCLIN-DEPENDENT KINASE 12 MODULATORS AND THERAPEUTIC USES THEREOF

  摘要：

  Provided herein are compounds having a structure of Formula (I) and pharmaceutically acceptable salts thereof which can act as modulators of cyclin-dependent kinase 12 (CDK12). Further disclosed herein are methods for treating cancer and cancer-related diseases and disorders, such as breast cancer, ovarian cancer, prostate cancer, and gastric cancer.

  公开号：

  WO2024148210A1

文献信息

• Protected Indazole Boronic Acid Pinacolyl Esters: Facile Syntheses and Studies of Reactivities in Suzuki-Miyaura Cross-Coupling and Hydroxydeboronation Reactions
  作者：Valérie Collot、François Crestey、Elodie Lohou、Silvia Stiebing、Sylvain Rault

  DOI：10.1055/s-0028-1087922

  日期：2009.3

  and efficient synthesis for the isolation of protected indazolylboronic esters. These com- pounds were synthesized by reaction between prepared protected haloindazoles and bis(pinacolato)diboron. The effects of solvent, temperature, reaction time, and the nature of halogen atom as well as protecting group were investigated. Additionaly, these com- pounds reacted either with aryl halides in a Suzuki-Miyaura

  该论文描述了一种用于分离受保护的吲唑基硼酸酯的快速有效的合成方法。这些化合物是通过制备的受保护的卤代吲唑和双（频哪醇）二硼反应合成的。考察了溶剂、温度、反应时间、卤原子性质和保护基等因素的影响。此外，这些化合物在 Suzuki-Miyaura 交叉偶联反应中与芳基卤化物反应或在羟基脱硼反应中与过氧化氢反应，显示出可能获得新的芳基和羟基吲唑库。我们小组长期以来一直对新的多功能化吲唑文库的设计和合成感兴趣，1 特别是那些源自色胺、血清素、褪黑激素或色氨酸的 2-氮杂生物电子等排体的文库。2
• Discovery of inhibitors of the mitotic kinase TTK based on N-(3-(3-sulfamoylphenyl)-1H-indazol-5-yl)-acetamides and carboxamides
  作者：Radoslaw Laufer、Grace Ng、Yong Liu、Narendra Kumar B. Patel、Louise G. Edwards、Yunhui Lang、Sze-Wan Li、Miklos Feher、Don E. Awrey、Genie Leung、Irina Beletskaya、Olga Plotnikova、Jacqueline M. Mason、Richard Hodgson、Xin Wei、Guodong Mao、Xunyi Luo、Ping Huang、Erin Green、Reza Kiarash、Dan Chi-Chia Lin、Marees Harris-Brandts、Fuqiang Ban、Vincent Nadeem、Tak W. Mak、Guohua J. Pan、Wei Qiu、Nickolay Y. Chirgadze、Henry W. Pauls

  DOI：10.1016/j.bmc.2014.06.027

  日期：2014.9

  TTK kinase was identified by in-house siRNA screen and pursued as a tractable, novel target for cancer treatment. A screening campaign and systematic optimization, supported by computer modeling led to an indazole core with key sulfamoylphenyl and acetamido moieties at positions 3 and 5, respectively, establishing a novel chemical class culminating in identification of 72 (CFI-400936). This potent inhibitor of TTK (IC50=3.6nM) demonstrated good activity in cell based assay and selectivity against a panel of human kinases. A co-complex TTK X-ray crystal structure and results of a xenograft study with TTK inhibitors from this class are described.