trans-3-[4-(1-benzenesulfonyl-5-methoxy-1H-indole-2-carbonyl)phenyl]-N-(tetrahydropyran-2-yloxy)acrylamide | 951655-75-7

• 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: trans-3-[4-(1-benzenesulfonyl-5-methoxy-1H-indole-2-carbonyl)phenyl]-N-(tetrahydropyran-2-yloxy)acrylamide
• 英文别名: (E)-3-[4-[1-(benzenesulfonyl)-5-methoxyindole-2-carbonyl]phenyl]-N-(oxan-2-yloxy)prop-2-enamide
• CAS: 951655-75-7
• 化学式: C₃₀H₂₈N₂O₇S
• 分子量: 560.628
• InChiKey: MJSRENHNVADWNE-SFQUDFHCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  trans-3-[4-(1-benzenesulfonyl-5-methoxy-1H-indole-2-carbonyl)phenyl]-N-(tetrahydropyran-2-yloxy)acrylamide 在 盐酸 作用下， 以 甲醇 为溶剂， 以56%的产率得到3-[4-(1-benzenesulfonyl-5-methoxy-1H-indole-2-carbonyl)-phenyl]-N-hydroxyacrylamide
  参考文献：
  名称：

  2-Aroylindoles and 2-Aroylbenzofurans with N-Hydroxyacrylamide Substructures as a Novel Series of Rationally Designed Histone Deacetylase Inhibitors

  摘要：

  Histone deacetylase (HDAC) inhibitors are considered to be drugs for targeted cancer therapy and second-generation HDIs are currently being tested in clinical trials. Here, we report on the synthesis and biological evaluation of a novel HDAC inhibitor scaffold with the hydroxamate Zn2+ complexing headgroup, selected from the 2-aroylindol motif. Inhibition of nuclear extract HDAC and recombinant HDAC I as well as induction of histone H3K(9+14) hyperacetylation mediated by E-N-hydroxy-(2-aroylindole)acrylamides or E-Nhydroxy-(2-aroylbenzofuran)acrylamides were studied. Moreover, the cytotoxic activity, the effects on the cell cycle, and historic H3S(10) phosphorylation of selected compounds were determined. By use of a panel of 24 different human tumor cell lines, mean IC50 values of the most potent analogues 6c and 7b were 0.75 and 0.65 mu M, respectively. The novel compounds were shown to be no substrates of the P-glycoprotein drug transporter. Comparable to N-1-hydroxy-N-8-phenyloctanediamide "2 (SAHA)", cells in the S phase of the cell cycle are depleted, with partial arrest in G1 and G2/M and finally induction of massive apoptosis.

  DOI：

  10.1021/jm0703136
• 作为产物：
  描述：

  4-(1,3-dioxolan-2-yl)benzoic acid 在 吡啶 、 sodium hydroxide 、 正丁基锂 、 氯化亚砜 、 高氯酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 trans-3-[4-(1-benzenesulfonyl-5-methoxy-1H-indole-2-carbonyl)phenyl]-N-(tetrahydropyran-2-yloxy)acrylamide
  参考文献：
  名称：

  2-Aroylindoles and 2-Aroylbenzofurans with N-Hydroxyacrylamide Substructures as a Novel Series of Rationally Designed Histone Deacetylase Inhibitors

  摘要：

  Histone deacetylase (HDAC) inhibitors are considered to be drugs for targeted cancer therapy and second-generation HDIs are currently being tested in clinical trials. Here, we report on the synthesis and biological evaluation of a novel HDAC inhibitor scaffold with the hydroxamate Zn2+ complexing headgroup, selected from the 2-aroylindol motif. Inhibition of nuclear extract HDAC and recombinant HDAC I as well as induction of histone H3K(9+14) hyperacetylation mediated by E-N-hydroxy-(2-aroylindole)acrylamides or E-Nhydroxy-(2-aroylbenzofuran)acrylamides were studied. Moreover, the cytotoxic activity, the effects on the cell cycle, and historic H3S(10) phosphorylation of selected compounds were determined. By use of a panel of 24 different human tumor cell lines, mean IC50 values of the most potent analogues 6c and 7b were 0.75 and 0.65 mu M, respectively. The novel compounds were shown to be no substrates of the P-glycoprotein drug transporter. Comparable to N-1-hydroxy-N-8-phenyloctanediamide "2 (SAHA)", cells in the S phase of the cell cycle are depleted, with partial arrest in G1 and G2/M and finally induction of massive apoptosis.

  DOI：

  10.1021/jm0703136

文献信息

• 2-Aroylindoles and 2-Aroylbenzofurans with <i>N-</i>Hydroxyacrylamide Substructures as a Novel Series of Rationally Designed Histone Deacetylase Inhibitors
  作者：Siavosh Mahboobi、Andreas Sellmer、Heymo Höcher、Christian Garhammer、Herwig Pongratz、Thomas Maier、Thomas Ciossek、Thomas Beckers

  DOI：10.1021/jm0703136

  日期：2007.9.1

  Histone deacetylase (HDAC) inhibitors are considered to be drugs for targeted cancer therapy and second-generation HDIs are currently being tested in clinical trials. Here, we report on the synthesis and biological evaluation of a novel HDAC inhibitor scaffold with the hydroxamate Zn2+ complexing headgroup, selected from the 2-aroylindol motif. Inhibition of nuclear extract HDAC and recombinant HDAC I as well as induction of histone H3K(9+14) hyperacetylation mediated by E-N-hydroxy-(2-aroylindole)acrylamides or E-Nhydroxy-(2-aroylbenzofuran)acrylamides were studied. Moreover, the cytotoxic activity, the effects on the cell cycle, and historic H3S(10) phosphorylation of selected compounds were determined. By use of a panel of 24 different human tumor cell lines, mean IC50 values of the most potent analogues 6c and 7b were 0.75 and 0.65 mu M, respectively. The novel compounds were shown to be no substrates of the P-glycoprotein drug transporter. Comparable to N-1-hydroxy-N-8-phenyloctanediamide "2 (SAHA)", cells in the S phase of the cell cycle are depleted, with partial arrest in G1 and G2/M and finally induction of massive apoptosis.