(5-Hydroxy-1-benzofuran-3-yl)-(5-hydroxy-2-methoxyphenyl)methanone | 1426074-91-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (5-Hydroxy-1-benzofuran-3-yl)-(5-hydroxy-2-methoxyphenyl)methanone
• 英文别名: (5-hydroxy-1-benzofuran-3-yl)-(5-hydroxy-2-methoxyphenyl)methanone
• CAS: 1426074-91-0
• 化学式: C₁₆H₁₂O₅
• 分子量: 284.268
• InChiKey: ZOFFNANPPAYKNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  79.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,5-二甲氧基苯乙酮 在 三溴化硼 作用下， 以 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 (2-hydroxy-5-methoxyphenyl)(5-hydroxybenzofuran-3-yl)methanone 、 (5-Hydroxy-1-benzofuran-3-yl)-(5-hydroxy-2-methoxyphenyl)methanone
  参考文献：
  名称：

  Identification of benzofuran-3-yl(phenyl)methanones as novel SIRT1 inhibitors: Binding mode, inhibitory mechanism and biological action

  摘要：

  SIRT1 is a NAD(+)-dependent deacetylase. Here we described new SIRT1 inhibitors with the scaffold of benzofuran-3-yl(phenyl)methanone. The inhibitors were predicted to bind in C-pocket of SIRT1, forming hydrophobic interactions with Phe273, Phe312 and Ile347. Introducing hydroxyl to meta position of phenyl may form H-bond with Asn346. Indeed, (2,5-dihydroxyphenyl)(5-hydroxy-1-benzofuran-3-yl) methanone (16), an analogue with hydroxyls at ortho and meta positions, showed greater inhibition. The binding mode was validated by structural modifications and kinetic studies. Since C-pocket is the site where the nicotinamide moiety of NAD(+) binds and the hydrolysis takes place, binding of 16 in C-pocket would block the transformation of NAD(+) to productive conformation and hence inhibit the deacetylase activity. Consistently, 16 inhibited SIRT1 through up-regulating p53 acetylation on cellular level. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.12.026

文献信息

• Identification of benzofuran-3-yl(phenyl)methanones as novel SIRT1 inhibitors: Binding mode, inhibitory mechanism and biological action
  作者：Jiahui Wu、Yi Li、Kaixian Chen、Hualiang Jiang、Ming-Hua Xu、Dongxiang Liu

  DOI：10.1016/j.ejmech.2012.12.026

  日期：2013.2

  SIRT1 is a NAD(+)-dependent deacetylase. Here we described new SIRT1 inhibitors with the scaffold of benzofuran-3-yl(phenyl)methanone. The inhibitors were predicted to bind in C-pocket of SIRT1, forming hydrophobic interactions with Phe273, Phe312 and Ile347. Introducing hydroxyl to meta position of phenyl may form H-bond with Asn346. Indeed, (2,5-dihydroxyphenyl)(5-hydroxy-1-benzofuran-3-yl) methanone (16), an analogue with hydroxyls at ortho and meta positions, showed greater inhibition. The binding mode was validated by structural modifications and kinetic studies. Since C-pocket is the site where the nicotinamide moiety of NAD(+) binds and the hydrolysis takes place, binding of 16 in C-pocket would block the transformation of NAD(+) to productive conformation and hence inhibit the deacetylase activity. Consistently, 16 inhibited SIRT1 through up-regulating p53 acetylation on cellular level. (C) 2012 Elsevier Masson SAS. All rights reserved.