4-(1H-indazol-5-yl)benzaldehyde | 1301189-01-4

• 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-(1H-indazol-5-yl)benzaldehyde
• 英文别名: 5-(4-Formylphenyl)-1H-indazole
• CAS: 1301189-01-4
• 化学式: C₁₄H₁₀N₂O
• 分子量: 222.246
• InChiKey: SJDMNAUNURWSJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  45.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(1H-indazol-5-yl)benzaldehyde 在 potassium carbonate 、 potassium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 41.0h， 生成 (E)-6-chloro-3-(3-(4-(1-ethyl-1H-indazol-5-yl)phenyl)-acryloyl)-4-phenylquinolin-2(1H)-one
  参考文献：
  名称：

  Synthetic Lethality in Pancreatic Cancer: Discovery of a New RAD51-BRCA2 Small Molecule Disruptor That Inhibits Homologous Recombination and Synergizes with Olaparib

  摘要：

  Synthetic lethality is an innovative framework for discovering novel anticancer drug candidates. One example is the use of PARP inhibitors (PARPi) in oncology patients with BRCA mutations. Here, we exploit a new paradigm based on the possibility of triggering synthetic lethality using only small organic molecules (dubbed "fully small-molecule-induced synthetic lethality"). We exploited this paradigm to target pancreatic cancer, one of the major unmet needs in oncology. We discovered a dihydroquinolone pyrazoline-based molecule (35d) that disrupts the RAD51-BRCA2 protein-protein interaction, thus mimicking the effect of BRCA2 mutation. 35d inhibits the homologous recombination in a human pancreatic adenocarcinoma cell line. In addition, it synergizes with olaparib (a PARPi) to trigger synthetic lethality. This strategy aims to widen the use of PARPi in BRCA-competent and olaparib-resistant cancers, making fully small-molecule-induced synthetic lethality an innovative approach toward unmet oncological needs.

  DOI：

  10.1021/acs.jmedchem.9b01526
• 作为产物：
  描述：

  5-溴吲唑 在 4-二甲氨基吡啶 、 四(三苯基膦)钯 caesium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 、 乙腈 为溶剂， 反应 18.25h， 生成 4-(1H-indazol-5-yl)benzaldehyde
  参考文献：
  名称：

  [EN] BENZIMIDAZOLES AS FATTY ACID SYNTHASE INHIBITORS
  [FR] BENZIMIDAZOLES UTILISÉS EN TANT QU'INHIBITEURS DE L'ACIDE GRAS SYNTHASE

  摘要：

  本发明涉及使用苯并咪唑衍生物来调节，特别是抑制脂肪酸合成酶（FAS）的活性或功能。适当地，本发明涉及在癌症治疗中使用苯并咪唑。

  公开号：

  WO2011056635A1

文献信息

• [EN] AZABENZIMIDAZOLES AS FATTY ACID SYNTHASE INHIBITORS<br/>[FR] AZABENZAMIDAZOLES COMME INHIBITEURS D'ACIDE GRAS SYNTHASE
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011066211A1

  公开（公告）日：2011-06-03

  This invention relates to the use of azabenzimidazole derivatives for the modulation, notably the inhibition of the activity or function of fatty acid synthase (FAS). Suitably, the present invention relates to the use of azabenzimidazoles in the treatment of cancer.

  这项发明涉及使用吡唑苯并咪唑衍生物来调节，特别是抑制脂肪酸合成酶（FAS）的活性或功能。适当地，本发明涉及在癌症治疗中使用吡唑苯并咪唑。
• [EN] COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF TUMORS<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR LE TRAITEMENT DE TUMEURS
  申请人：FONDAZIONE ST ITALIANO TECNOLOGIA

  公开号：WO2021116999A1

  公开（公告）日：2021-06-17

  The present invention relates to compounds of Formula (Ia) or pharmaceutically acceptable salts, hydrates, solvates, clathrates, polymorphs, stereoisomers thereof. It further discloses a pharmaceutical composition comprising compounds of Formula (Ia) and the use of compounds of Formula (Ib), in particular for the use in the treatment of diseases or disorders wherein disrupting Rad51-BRCA2 interaction is beneficial.

  本发明涉及式(Ia)的化合物或药学上可接受的盐、水合物、溶剂合物、包合物、多晶型、立体异构体，还揭示了包含式(Ia)的化合物的药物组合物以及利用式(Ib)的化合物，特别是用于治疗破坏Rad51-BRCA2相互作用有益的疾病或紊乱的用途。
• AZABENZIMIDAZOLES AS FATTY ACID SYNTHASE INHIBITORS
  申请人：Chaudhari Amita M.

  公开号：US20120295915A1

  公开（公告）日：2012-11-22

  Disclosed are compounds having Formula (I), wherein R 1 , R 2 , R 3 , R 4 , Ra, Rb, X, Y, m, and n are defined herein and methods of using the same.

  本发明涉及具有公式（I）的化合物，其中R1、R2、R3、R4、Ra、Rb、X、Y、m和n在此定义，并且使用这些化合物的方法。
• BENZIMIDAZOLES AS FATTY ACID SYNTHASE INHIBITORS
  申请人：Dock Steven

  公开号：US20120208827A1

  公开（公告）日：2012-08-16

  This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of fatty acid synthase (FAS). Suitably, the present invention relates to the use of benzimidazoles in the treatment of cancer.

  本发明涉及使用苯并咪唑衍生物来调节，特别是抑制脂肪酸合酶（FAS）的活性或功能。适当地，本发明涉及使用苯并咪唑类化合物治疗癌症。
• Synthetic Lethality in Pancreatic Cancer: Discovery of a New RAD51-BRCA2 Small Molecule Disruptor That Inhibits Homologous Recombination and Synergizes with Olaparib
  作者：Greta Bagnolini、Domenico Milano、Marcella Manerba、Fabrizio Schipani、Jose Antonio Ortega、Dario Gioia、Federico Falchi、Andrea Balboni、Fulvia Farabegoli、Francesca De Franco、Janet Robertson、Roberto Pellicciari、Isabella Pallavicini、Sebastiano Peri、Saverio Minucci、Stefania Girotto、Giuseppina Di Stefano、Marinella Roberti、Andrea Cavalli

  DOI：10.1021/acs.jmedchem.9b01526

  日期：2020.3.12

  Synthetic lethality is an innovative framework for discovering novel anticancer drug candidates. One example is the use of PARP inhibitors (PARPi) in oncology patients with BRCA mutations. Here, we exploit a new paradigm based on the possibility of triggering synthetic lethality using only small organic molecules (dubbed "fully small-molecule-induced synthetic lethality"). We exploited this paradigm to target pancreatic cancer, one of the major unmet needs in oncology. We discovered a dihydroquinolone pyrazoline-based molecule (35d) that disrupts the RAD51-BRCA2 protein-protein interaction, thus mimicking the effect of BRCA2 mutation. 35d inhibits the homologous recombination in a human pancreatic adenocarcinoma cell line. In addition, it synergizes with olaparib (a PARPi) to trigger synthetic lethality. This strategy aims to widen the use of PARPi in BRCA-competent and olaparib-resistant cancers, making fully small-molecule-induced synthetic lethality an innovative approach toward unmet oncological needs.