(4S)-4-(1H-indol-3-ylmethyl)-1,3-thiazolidine-2-thione | 1448350-59-1

• 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: (4S)-4-(1H-indol-3-ylmethyl)-1,3-thiazolidine-2-thione
• CAS: 1448350-59-1
• 化学式: C₁₂H₁₂N₂S₂
• 分子量: 248.373
• InChiKey: FOZTZHYTESVRFO-VIFPVBQESA-N

物化性质

• 沸点：
  454.9±37.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4S)-4-(1H-indol-3-ylmethyl)-1,3-thiazolidine-2-thione 、 N-(2-aminophenyl)-4-(chloromethyl)benzamide 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 16.5h， 以86%的产率得到N-(2-aminophenyl)-4-({[(4S)-4-(1H-indol-3-ylmethyl)-4,5-dihydro-1,3-thiazol-2-yl]sulfanyl}methyl)benzamide
  参考文献：
  名称：

  Discovery of Potent, Isoform-Selective Inhibitors of Histone Deacetylase Containing Chiral Heterocyclic Capping Groups and a N-(2-Aminophenyl)benzamide Binding Unit

  摘要：

  The synthesis of a novel series of potent chiral inhibitors of histone deacetylase (HDAC) is described that contain a heterocyclic capping group and a N-(2-aminophenyl)benzamide unit that binds in the active site. In vitro assays for the inhibition of HDAC1, HDAC2, HDAC3-NCoR1, and HDAC8 by the N-(2-aminophenyl)benzmide 24a gave respective IC50 values of 930, 85, 12, and 4100 nM, exhibiting class I selectivity and potent inhibition of HDAC3-NCoR1. Both imidazolinone and thiazoline rings are shown to be effective replacements for the pyrimidine ring present in many other 2-(aminophenyl)benzamides previously reported, an example of each ring system at 1 mu M causing an increase in histone H3K9 acetylation in the human cell lines Jurkat and HeLa and an increase in cell death consistent with induction of apoptosis. Inhibition of the growth of MCF-7, A549, DU145, and HCT116 cell lines by 24a was observed, with respective IC50 values of 5.4, 5.8, 6.4, and 2.2 mM.

  DOI：

  10.1021/jm400634n
• 作为产物：
  描述：

  L-色氨酸 在 sodium tetrahydroborate 、 碘 、 potassium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 17.0h， 生成 (4S)-4-(1H-indol-3-ylmethyl)-1,3-thiazolidine-2-thione
  参考文献：
  名称：

  Discovery of Potent, Isoform-Selective Inhibitors of Histone Deacetylase Containing Chiral Heterocyclic Capping Groups and a N-(2-Aminophenyl)benzamide Binding Unit

  摘要：

  The synthesis of a novel series of potent chiral inhibitors of histone deacetylase (HDAC) is described that contain a heterocyclic capping group and a N-(2-aminophenyl)benzamide unit that binds in the active site. In vitro assays for the inhibition of HDAC1, HDAC2, HDAC3-NCoR1, and HDAC8 by the N-(2-aminophenyl)benzmide 24a gave respective IC50 values of 930, 85, 12, and 4100 nM, exhibiting class I selectivity and potent inhibition of HDAC3-NCoR1. Both imidazolinone and thiazoline rings are shown to be effective replacements for the pyrimidine ring present in many other 2-(aminophenyl)benzamides previously reported, an example of each ring system at 1 mu M causing an increase in histone H3K9 acetylation in the human cell lines Jurkat and HeLa and an increase in cell death consistent with induction of apoptosis. Inhibition of the growth of MCF-7, A549, DU145, and HCT116 cell lines by 24a was observed, with respective IC50 values of 5.4, 5.8, 6.4, and 2.2 mM.

  DOI：

  10.1021/jm400634n

文献信息

• Discovery of Potent, Isoform-Selective Inhibitors of Histone Deacetylase Containing Chiral Heterocyclic Capping Groups and a <i>N</i>-(2-Aminophenyl)benzamide Binding Unit
  作者：Charles M. Marson、Christopher J. Matthews、Elena Yiannaki、Stephen J. Atkinson、Peter E. Soden、Lena Shukla、Nermina Lamadema、N. Shaun B. Thomas

  DOI：10.1021/jm400634n

  日期：2013.8.8

  The synthesis of a novel series of potent chiral inhibitors of histone deacetylase (HDAC) is described that contain a heterocyclic capping group and a N-(2-aminophenyl)benzamide unit that binds in the active site. In vitro assays for the inhibition of HDAC1, HDAC2, HDAC3-NCoR1, and HDAC8 by the N-(2-aminophenyl)benzmide 24a gave respective IC50 values of 930, 85, 12, and 4100 nM, exhibiting class I selectivity and potent inhibition of HDAC3-NCoR1. Both imidazolinone and thiazoline rings are shown to be effective replacements for the pyrimidine ring present in many other 2-(aminophenyl)benzamides previously reported, an example of each ring system at 1 mu M causing an increase in histone H3K9 acetylation in the human cell lines Jurkat and HeLa and an increase in cell death consistent with induction of apoptosis. Inhibition of the growth of MCF-7, A549, DU145, and HCT116 cell lines by 24a was observed, with respective IC50 values of 5.4, 5.8, 6.4, and 2.2 mM.