(S)-1-((1,3-di(9H-carbazol-9-yl)propan-2-yl)oxy)-3-(isopropylamino)propan-2-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (S)-1-((1,3-di(9H-carbazol-9-yl)propan-2-yl)oxy)-3-(isopropylamino)propan-2-ol
• 英文别名: (2S)-1-[1,3-di(carbazol-9-yl)propan-2-yloxy]-3-(propan-2-ylamino)propan-2-ol
• 化学式: C₃₃H₃₅N₃O₂
• 分子量: 505.66
• InChiKey: BLTONWSCODZCNA-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  51.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (S)-9,9′-(2-(oxiran-2-ylmethoxy)propane-1,3-diyl)bis(9H-carbazole) 、 异丙胺 以 异丙醇 为溶剂， 反应 1.0h， 以44%的产率得到(S)-1-((1,3-di(9H-carbazol-9-yl)propan-2-yl)oxy)-3-(isopropylamino)propan-2-ol
  参考文献：
  名称：

  Identifying Novel Selective Non-Nucleoside DNA Methyltransferase 1 Inhibitors through Docking-Based Virtual Screening

  摘要：

  The DNA methyltransferases (DNMTs) found in mammals include DNMT1, DNMT3A, and DNMT3B and are attractive targets in cancer chemotherapy. DNMT1 was the first among the DNMTs to be characterized, and it is responsible for maintaining DNA methylation patterns. A number of DNMT inhibitors have been reported, but most of them are nucleoside analogs that can lead to toxic side effects and lack specificity. By combining docking-based virtual screening with biochemical analyses, we identified a novel compound, DC_05. DC_05 is a non-nucleoside DNMT1 inhibitor with low micromolar IC50 values and significant selectivity toward other AdoMet-dependent protein methyltransferases. Through a process of similarity-based analog searching, compounds DC_501 and DC_517 were found to be more potent than DC_05. These three potent compounds significantly inhibited cancer cell proliferation. The structure-activity relationship (SAR) and binding modes of these inhibitors were also analyzed to assist in the future development of more potent and more specific DNMT1 inhibitors.

  DOI：

  10.1021/jm501134e