5-(3-bromophenyl)-4-[(2-hydroxynaphthalen-1-yl)methyl]-2,3-dihydro-1H-pyrazol-3-one | 1597709-80-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(3-bromophenyl)-4-[(2-hydroxynaphthalen-1-yl)methyl]-2,3-dihydro-1H-pyrazol-3-one
• 英文别名: 5-(3-Bromophenyl)-4-[(2-hydroxynaphthalen-1-yl)methyl]-1,2-dihydropyrazol-3-one；5-(3-bromophenyl)-4-[(2-hydroxynaphthalen-1-yl)methyl]-1,2-dihydropyrazol-3-one
• CAS: 1597709-80-2
• 化学式: C₂₀H₁₅BrN₂O₂
• 分子量: 395.255
• InChiKey: VEEYLFLIEZGENP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  61.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-(3-bromobenzoyl)-1H,2H-naphtho[2,1-b]pyran-3-one 在 肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 以25 mg的产率得到5-(3-bromophenyl)-4-[(2-hydroxynaphthalen-1-yl)methyl]-2,3-dihydro-1H-pyrazol-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

• 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.