2-(4'-trifluoromethylbenzoyl)-3H-benzo[f]chromen-3-one | 1148118-33-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: 2-(4'-trifluoromethylbenzoyl)-3H-benzo[f]chromen-3-one
• 英文别名: 2-(4-trifluoromethylbenzoyl)-3H-benzo[f ]chromen-3-one；2-(4-trifluoromethyl-benzoyl)-benzo[f]chromen-3-one；2-[4-(Trifluoromethyl)benzoyl]benzo[f]chromen-3-one
• CAS: 1148118-33-5
• 化学式: C₂₁H₁₁F₃O₃
• 分子量: 368.312
• InChiKey: FJHPRZJANMFFNT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(4'-trifluoromethylbenzoyl)-3H-benzo[f]chromen-3-one 在 sodium tetrahydroborate 作用下， 以 吡啶 为溶剂， 反应 2.0h， 以89%的产率得到2-(4'-trifluoromethylbenzoyl)-1,2-dihydro-benzo[f]chromen-3-one
  参考文献：
  名称：

  Novel Cambinol Analogs as Sirtuin Inhibitors: Synthesis, Biological Evaluation, and Rationalization of Activity

  摘要：

  The tenovins and cambinol are two classes of sirtuin inhibitor that exhibit antitumor activity in preclinical models. This report describes modifications to the core structure of cambinol, in particular by incorporation of substitutents at the N1-position, which lead to increased potency and modified selectivity. These improvements have been rationalized using molecular modeling techniques. The expected functional selectivity in cells was also observed for both a SIRT1 and a SIRT2 selective analog.

  DOI：

  10.1021/jm8014298
• 作为产物：
  描述：

  2-萘酚 在 哌啶 、 四氯化钛 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 2.25h， 生成 2-(4'-trifluoromethylbenzoyl)-3H-benzo[f]chromen-3-one
  参考文献：
  名称：

  Development of Pyrazolone and Isoxazol-5-one Cambinol Analogues as Sirtuin Inhibitors

  摘要：

  Sirtuins are a family of NAD+-dependent protein deacetylases that play critical roles in epigenetic regulation, stress responses, and cellular aging in eukaryotic cells. In an effort to identify small molecule inhibitors of sirtuins for potential use as chemotherapeutics as well as tools to modulate sirtuin activity, we previously identified a nonselective sirtuin inhibitor called cambinol (IC50 approximate to 50 mu M for SIRT1 and SIRT2) with in vitro and in vivo antilymphoma activity. In the current study, we used saturation transfer difference (STD) NMR experiments with recombinant SIRT1 and 20 to map parts of the inhibitor that interacted with the protein. Our ongoing efforts to optimize cambinol analogues for potency and selectivity have resulted in the identification of isoform selective analogues: 17 with >7.8-fold selectivity for SIRT1, 24 with >15.4-fold selectivity for SIRT2, and 8 with 6.8- and 5.3-fold selectivity for SIRT3 versus SIRT1 and SIRT2, respectively. In vitro cytotoxicity studies with these compounds as well as EX527, a potent and selective SIRT1 inhibitor, suggest that antilymphoma activity of this compound class. may be predominantly due to SIRT2 inhibition.

  DOI：

  10.1021/jm4018064

文献信息

• Novel Cambinol Analogs as Sirtuin Inhibitors: Synthesis, Biological Evaluation, and Rationalization of Activity
  作者：Federico Medda、Rupert J. M. Russell、Maureen Higgins、Anna R. McCarthy、Johanna Campbell、Alexandra M. Z. Slawin、David P. Lane、Sonia Lain、Nicholas J. Westwood

  DOI：10.1021/jm8014298

  日期：2009.5.14

  The tenovins and cambinol are two classes of sirtuin inhibitor that exhibit antitumor activity in preclinical models. This report describes modifications to the core structure of cambinol, in particular by incorporation of substitutents at the N1-position, which lead to increased potency and modified selectivity. These improvements have been rationalized using molecular modeling techniques. The expected functional selectivity in cells was also observed for both a SIRT1 and a SIRT2 selective analog.
• Development of Pyrazolone and Isoxazol-5-one Cambinol Analogues as Sirtuin Inhibitors
  作者：Sumit S. Mahajan、Michele Scian、Smitha Sripathy、Jeff Posakony、Uyen Lao、Taylor K. Loe、Vid Leko、Angel Thalhofer、Aaron D. Schuler、Antonio Bedalov、Julian A. Simon

  DOI：10.1021/jm4018064

  日期：2014.4.24

  Sirtuins are a family of NAD+-dependent protein deacetylases that play critical roles in epigenetic regulation, stress responses, and cellular aging in eukaryotic cells. In an effort to identify small molecule inhibitors of sirtuins for potential use as chemotherapeutics as well as tools to modulate sirtuin activity, we previously identified a nonselective sirtuin inhibitor called cambinol (IC50 approximate to 50 mu M for SIRT1 and SIRT2) with in vitro and in vivo antilymphoma activity. In the current study, we used saturation transfer difference (STD) NMR experiments with recombinant SIRT1 and 20 to map parts of the inhibitor that interacted with the protein. Our ongoing efforts to optimize cambinol analogues for potency and selectivity have resulted in the identification of isoform selective analogues: 17 with >7.8-fold selectivity for SIRT1, 24 with >15.4-fold selectivity for SIRT2, and 8 with 6.8- and 5.3-fold selectivity for SIRT3 versus SIRT1 and SIRT2, respectively. In vitro cytotoxicity studies with these compounds as well as EX527, a potent and selective SIRT1 inhibitor, suggest that antilymphoma activity of this compound class. may be predominantly due to SIRT2 inhibition.