tert-butyl N-(2-{4-[({[(1S)-2-hydroxy-1-phenylethyl]carbamothioyl}amino)methyl]benzamido}phenyl)carbamate | 1448350-41-1

• 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: tert-butyl N-(2-{4-[({[(1S)-2-hydroxy-1-phenylethyl]carbamothioyl}amino)methyl]benzamido}phenyl)carbamate
• 英文别名: tert-butyl (S)-2-(2-(4-((3-(2-hydroxy-1-phenylethyl)thioureido)methyl)benzamido)phenyl)carbamate；tert-butyl N-[2-[[4-[[[(1S)-2-hydroxy-1-phenylethyl]carbamothioylamino]methyl]benzoyl]amino]phenyl]carbamate
• CAS: 1448350-41-1
• 化学式: C₂₈H₃₂N₄O₄S
• 分子量: 520.652
• InChiKey: GBSGSHOGQZADFU-XMMPIXPASA-N

物化性质

• 密度：
  1.286±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  144
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl N-(2-{4-[({[(1S)-2-hydroxy-1-phenylethyl]carbamothioyl}amino)methyl]benzamido}phenyl)carbamate 在 盐酸 作用下， 以 水 为溶剂， 反应 1.25h， 以24%的产率得到N-(2-aminophenyl)-4-({[(4S)-4-phenyl-4,5-dihydro-1,3-thiazol-2-yl]amino}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：

  4-((2,2,2-trifluoroacetamido)methyl)benzoic acid 在 甲醇 、 草酰氯 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 40.85h， 生成 tert-butyl N-(2-{4-[({[(1S)-2-hydroxy-1-phenylethyl]carbamothioyl}amino)methyl]benzamido}phenyl)carbamate
  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

• Potent and Selective Inhibitors of Histone Deacetylase-3 Containing Chiral Oxazoline Capping Groups and a <i>N</i>-(2-Aminophenyl)-benzamide Binding Unit
  作者：Charles M. Marson、Christopher J. Matthews、Stephen J. Atkinson、Nermina Lamadema、N. Shaun B. Thomas

  DOI：10.1021/acs.jmedchem.5b00545

  日期：2015.9.10

  A novel series of potent chiral inhibitors of histone deacetylase (HDAC) is described that contains an oxazoline capping group and a N-(2-aminophenyl)-benzamide unit. Among several new inhibitors of this type exhibiting Class I selectivity and potent inhibition of HDAC3-NCoR2, in vitro assays for the inhibition of HDAC1, HDAC2, and HDAC3-NCoR2 by N-(2-aminophenyl)-benzamide 15k gave respective IC50 values of 80, 110, and 6 nM. Weak inhibition of all other HDAC isoforms (HDAC4, 5, 6, 7, and 9: IC50 > 100 000 nM; HDAC8: IC50 = 25 000 nM; HDAC10: IC50 > 4000 nM; HDAC11: IC50 > 2000 nM) confirmed the Class I selectivity of 15k 2-Aminoimidazolinyl, 2-thioimidazolinyl, and 2-aminooxazolinyl units were shown to be effective replacements for the pyrimidine ring present in many other 2-(aminophenyl)-benzamides previously reported, but the 2-aminooxazolinyl unit was the most potent in inhibiting HDAC3-NCoR2. Many of the new HDAC inhibitors showed higher solubilities and lower binding to human serum albumin than that of Mocetinostat. Increases in histone H3K9 acetylation in the human cell lines U937 and PC-3 was observed for all three oxazolinyl inhibitors evaluated; those HDAC inhibitors also lowered cyclin E expression in U937 cells but not in PC-3 cells, indicating underlying differences in the mechanisms of action of the inhibitors on those two cell lines.
• 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.