| 2326563-28-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• CAS: 2326563-28-2
• 化学式: C₄H₆OS₂.2Na
• 分子量: 180.2
• InChiKey: IMBNTKMADSKQCA-UHFFFAOYSA-N

反应信息

• 作为反应物：
  描述：

  碘甲烷 、 在 sodium t-butanolate 、 盐酸 、 dimethyl sulfide borane 、 甲醇 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 甲醇 、 叔丁醇 、 水 、 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 以38 %的产率得到1-((R)-1-((1r,4R)-4-(3-cyclopropoxyazetidin-1-yl)cyclohexyl)ethyl)-2-methyl-N-((6-methyl-4-(methylthio)-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamide
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of Second Generation EZH2 Inhibitors with Long Residence Time

  摘要：

  Histone methyltransferase EZH2, which is the catalytic subunit of the PRC2 complex, catalyzes the methylation of histone H3K27-a transcriptionally repressive post-translational modification (PTM). EZH2 is commonly mutated in hematologic malignancies and frequently overexpressed in solid tumors, where its expression level often correlates with poor prognosis. First generation EZH2 inhibitors are beginning to show clinical benefit, and we believe that a second generation EZH2 inhibitor could further build upon this foundation to fully realize the therapeutic potential of EZH2 inhibition. During our medicinal chemistry campaign, we identified 4-thiomethyl pyridone as a key modification that led to significantly increased potency and prolonged residence time. Leveraging this finding, we optimized a series of EZH2 inhibitors, with enhanced antitumor activity and improved physiochemical properties, which have the potential to expand the clinical use of EZH2 inhibition.

  DOI：

  10.1021/acsmedchemlett.0c00045