6-((3-fluorobenzyl)thio)-1,5-dimethyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 6-((3-fluorobenzyl)thio)-1,5-dimethyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one
• 英文别名: 6-[(3-Fluorophenyl)methylsulfanyl]-1,5-dimethylpyrazolo[3,4-d]pyrimidin-4-one；6-[(3-fluorophenyl)methylsulfanyl]-1,5-dimethylpyrazolo[3,4-d]pyrimidin-4-one
• 化学式: C₁₄H₁₃FN₄OS
• 分子量: 304.348
• InChiKey: MQGOJYRVAWOXEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  75.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-氨基-1-甲基吡唑-4-甲酸乙酯 在 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 、 mineral oil 为溶剂， 反应 6.34h， 生成 6-((3-fluorobenzyl)thio)-1,5-dimethyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one
  参考文献：
  名称：

  [EN] SMALL MOLECULE INHIBITORS OF ALDH AND USES THEREOF
  [FR] INHIBITEURS À PETITES MOLÉCULES D'ALDH ET UTILISATIONS ASSOCIÉES

  摘要：

  这项发明属于药物化学领域。特别是，该发明涉及一类具有噻吩嘧啶酮结构的新颖小分子，它们作为ALDH蛋白的抑制剂，以及它们作为治疗癌症和其他疾病的疗法的使用。

  公开号：

  WO2017223086A1

文献信息

• Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer Chemotherapy
  作者：Brandt C. Huddle、Edward Grimley、Cameron D. Buchman、Mikhail Chtcherbinine、Bikash Debnath、Pooja Mehta、Kun Yang、Cynthia A. Morgan、Siwei Li、Jeremy Felton、Duxin Sun、Geeta Mehta、Nouri Neamati、Ronald J. Buckanovich、Thomas D. Hurley、Scott D. Larsen

  DOI：10.1021/acs.jmedchem.8b00930

  日期：2018.10.11

  Aldehyde dehydrogenase (ALDH) activity is commonly used as a marker to identify cancer stem-like cells. The three ALDH1A isoforms have all been individually implicated in cancer stem-like cells and in chemoresistance; however, which isoform is preferentially expressed varies between cell lines. We sought to explore the structural determinants of ALDH1A isoform selectivity in a series of small-molecule inhibitors in support of research into the role of ALDH1A in cancer stem cells. An SAR campaign guided by a cocrystal structure of the HTS hit CM39 (7) with ALDH1A1 afforded first-in-class inhibitors of the ALDH1A subfamily with excellent selectivity over the homologous ALDH2 isoform. We also discovered the first reported modestly selective single isoform 1A2 and 1A3 inhibitors. Two compounds, 13g and 13h, depleted the CD133(+) putative cancer stem cell pool, synergized with cisplatin, and achieved efficacious concentrations in vivo following IP administration. Compound 13h additionally synergized with cisplatin in a patient-derived ovarian cancer spheroid model.
• SMALL MOLECULE INHIBITORS OF ALDH AND USES THEREOF
  申请人：The Regents of The University of Michigan

  公开号：EP3471712A1

  公开（公告）日：2019-04-24