6,7-bis((3-fluoro-4-methoxybenzyl)oxy)-2,2-dimethylchroman-4-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 6,7-bis((3-fluoro-4-methoxybenzyl)oxy)-2,2-dimethylchroman-4-one
• 英文别名: 6,7-bis[(3-fluoro-4-methoxyphenyl)methoxy]-2,2-dimethyl-3H-chromen-4-one
• 化学式: C₂₇H₂₆F₂O₆
• 分子量: 484.497
• InChiKey: ZTNFAFCDLXHCQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6,7-bis((3-fluoro-4-methoxybenzyl)oxy)-2,2-dimethylchroman-4-one 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以71%的产率得到6,7-bis((3-fluoro-4-methoxybenzyl)oxy)-2,2-dimethylchroman-4-ol
  参考文献：
  名称：

  Discovery of Small Molecules as Multi-Toll-like Receptor Agonists with Proinflammatory and Anticancer Activities

  摘要：

  Therapies based on activation of multiple Toll-like receptors (TLRs) may offer superior therapeutic profiles than that of single TLR activation. To, discover new small molecules that could activate multiple TLRs, we performed a cell-based high-throughput, screening of a small-molecule library based on TLR3-mediated NF-kappa B activation. Subsequent structural optimization and counterscreening of other TLRs produced the first small molecule 17e (CU-CPT17e), capable of simultaneously activating TLRs 3) 8, and 9. Biochemical studies demonstrated that 17e could induce a strong immune response via the production of various cytokines in human monocytic THP-1 cells. Furthermore, 17e inhibited the proliferation of HeLa cancer cells by triggering apoptosis and arresting the-cell. cycle at the S phase. These results Showcase potential therapeutic applications of 17e it both vaccine adjuvants and anticancer therapies based on multi-TLR activation.

  DOI：

  10.1021/acs.jmedchem.7b00419
• 作为产物：
  描述：

  6,7-二甲氧基-2,2-二甲基-4-色满酮 在 三溴化硼 、 potassium carbonate 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 生成 6,7-bis((3-fluoro-4-methoxybenzyl)oxy)-2,2-dimethylchroman-4-one
  参考文献：
  名称：

  Discovery of Small Molecules as Multi-Toll-like Receptor Agonists with Proinflammatory and Anticancer Activities

  摘要：

  Therapies based on activation of multiple Toll-like receptors (TLRs) may offer superior therapeutic profiles than that of single TLR activation. To, discover new small molecules that could activate multiple TLRs, we performed a cell-based high-throughput, screening of a small-molecule library based on TLR3-mediated NF-kappa B activation. Subsequent structural optimization and counterscreening of other TLRs produced the first small molecule 17e (CU-CPT17e), capable of simultaneously activating TLRs 3) 8, and 9. Biochemical studies demonstrated that 17e could induce a strong immune response via the production of various cytokines in human monocytic THP-1 cells. Furthermore, 17e inhibited the proliferation of HeLa cancer cells by triggering apoptosis and arresting the-cell. cycle at the S phase. These results Showcase potential therapeutic applications of 17e it both vaccine adjuvants and anticancer therapies based on multi-TLR activation.

  DOI：

  10.1021/acs.jmedchem.7b00419

文献信息

• Discovery of Small Molecules as Multi-Toll-like Receptor Agonists with Proinflammatory and Anticancer Activities
  作者：Lei Zhang、Varun Dewan、Hang Yin

  DOI：10.1021/acs.jmedchem.7b00419

  日期：2017.6.22

  Therapies based on activation of multiple Toll-like receptors (TLRs) may offer superior therapeutic profiles than that of single TLR activation. To, discover new small molecules that could activate multiple TLRs, we performed a cell-based high-throughput, screening of a small-molecule library based on TLR3-mediated NF-kappa B activation. Subsequent structural optimization and counterscreening of other TLRs produced the first small molecule 17e (CU-CPT17e), capable of simultaneously activating TLRs 3) 8, and 9. Biochemical studies demonstrated that 17e could induce a strong immune response via the production of various cytokines in human monocytic THP-1 cells. Furthermore, 17e inhibited the proliferation of HeLa cancer cells by triggering apoptosis and arresting the-cell. cycle at the S phase. These results Showcase potential therapeutic applications of 17e it both vaccine adjuvants and anticancer therapies based on multi-TLR activation.