17-{N-[3,3-(diphenyl)propyl]-N-[2-(mesitylene)sulfonyl]}amino-13-N-[2-(mesitylene)sulfonyl]-1-N-[4-(N-(2-aminophenyl)benzamido)methyl]amino-1,8-dioxo-9,13-diazaheptadecanamide | 1020675-45-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 17-{N-[3,3-(diphenyl)propyl]-N-[2-(mesitylene)sulfonyl]}amino-13-N-[2-(mesitylene)sulfonyl]-1-N-[4-(N-(2-aminophenyl)benzamido)methyl]amino-1,8-dioxo-9,13-diazaheptadecanamide
• CAS: 1020675-45-9
• 化学式: C₆₂H₇₈N₆O₇S₂
• 分子量: 1083.47
• InChiKey: SBMHLEASAFUBPW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.22
• 重原子数：
  77.0
• 可旋转键数：
  29.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  188.08
• 氢给体数：
  4.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  17-{N-[3,3-(diphenyl)propyl]-N-[2-(mesitylene)sulfonyl]}amino-13-N-[2-(mesitylene)sulfonyl]-1-N-[4-(N-(2-aminophenyl)benzamido)methyl]amino-1,8-dioxo-9,13-diazaheptadecanamide 在 氢溴酸 、 溶剂黄146 、 苯酚 作用下， 以 乙酸乙酯 为溶剂， 反应 15.0h， 以76.7%的产率得到17-N-[3,3-(diphenyl)propyl]amino-1-N-[4-(N-(2-aminophenyl)benzamido)methyl]amino-1,8-dioxo-9,13-diazaheptadecanamide dihydrobromide
  参考文献：
  名称：

  Polyaminohydroxamic Acids and Polyaminobenzamides as Isoform Selective Histone Deacetylase Inhibitors

  摘要：

  A series of polyaminohydroxamic acids (PAHAs) and polyaminobenzamides (PABAs) were synthesized and evaluated as isoform-selective histone deacetylase (HDAC) inhibitors. These analogues contain a polyamine chain to increase affinity for chromatin and facilitate cellular import. Seven PAHAs inhibited HDAC >50% (1 mu M), and two PABAs inhibited HDAC >50% (5 mu M). Compound 17 increased acetylated a-tubulin in HCT1 16 colon tumor cells 253-fold but only modestly increased p21(waf1) and acetylated histories 3 and 4, suggesting that 17 selectively inhibits HDAC 6. PABA 22 alone minimally increased p21(waf1) and acetylated histories 3 and 4 but caused dose-dependent increases in p21(waf1) in combination with 0.1 mu M 5-azadeoxycytidine. Finally, 22 appeared to be a substrate for the polyamine transport system. None of these compounds were cytotoxic at 100 mu M. PAHAs and PABAs exhibit strikingly different cellular effects from SAHA and have the potential for use in combination antitumor therapies with reduced toxicity.

  DOI：

  10.1021/jm701384x
• 作为产物：
  描述：

  17-{N-[3,3-(diphenyl)propyl]-N-[2-(mesitylene)sulfonyl]}amino-13-N-[2-(mesitylene)sulfonyl]-1-N-[4-(carboxy)benzyl]amino-1,8-dioxo-9,13-diazaheptadecanamide 、 N-Boc-1,2-亚苯基二胺 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以84.2%的产率得到17-{N-[3,3-(diphenyl)propyl]-N-[2-(mesitylene)sulfonyl]}amino-13-N-[2-(mesitylene)sulfonyl]-1-N-[4-(N-(2-aminophenyl)benzamido)methyl]amino-1,8-dioxo-9,13-diazaheptadecanamide
  参考文献：
  名称：

  Polyaminohydroxamic Acids and Polyaminobenzamides as Isoform Selective Histone Deacetylase Inhibitors

  摘要：

  A series of polyaminohydroxamic acids (PAHAs) and polyaminobenzamides (PABAs) were synthesized and evaluated as isoform-selective histone deacetylase (HDAC) inhibitors. These analogues contain a polyamine chain to increase affinity for chromatin and facilitate cellular import. Seven PAHAs inhibited HDAC >50% (1 mu M), and two PABAs inhibited HDAC >50% (5 mu M). Compound 17 increased acetylated a-tubulin in HCT1 16 colon tumor cells 253-fold but only modestly increased p21(waf1) and acetylated histories 3 and 4, suggesting that 17 selectively inhibits HDAC 6. PABA 22 alone minimally increased p21(waf1) and acetylated histories 3 and 4 but caused dose-dependent increases in p21(waf1) in combination with 0.1 mu M 5-azadeoxycytidine. Finally, 22 appeared to be a substrate for the polyamine transport system. None of these compounds were cytotoxic at 100 mu M. PAHAs and PABAs exhibit strikingly different cellular effects from SAHA and have the potential for use in combination antitumor therapies with reduced toxicity.

  DOI：

  10.1021/jm701384x