N-(2-aminophenyl)-4-(chloromethyl)benzamide | 1448350-60-4

• 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: N-(2-aminophenyl)-4-(chloromethyl)benzamide
• CAS: 1448350-60-4
• 化学式: C₁₄H₁₃ClN₂O
• 分子量: 260.723
• InChiKey: JLDGBGZRRRJYRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(2-aminophenyl)-4-(chloromethyl)benzamide 、 S-4-苄基噁唑烷-2-硫酮 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 16.5h， 以70%的产率得到(S)-N-(2-aminophenyl)-4-(((4-benzyl-4,5-dihydrooxazol-2-yl)thio)methyl)benzamide
  参考文献：
  名称：

  Potent and Selective Inhibitors of Histone Deacetylase-3 Containing Chiral Oxazoline Capping Groups and a N-(2-Aminophenyl)-benzamide Binding Unit

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.5b00545
• 作为产物：
  描述：

  N-Boc-1,2-亚苯基二胺 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 生成 N-(2-aminophenyl)-4-(chloromethyl)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

文献信息

• 一种组蛋白去乙酰化酶和热休克蛋白110KDa双靶点抑制剂及应用
  申请人：杭州师范大学

  公开号：CN116803983A

  公开（公告）日：2023-09-26

  本发明公开一种组蛋白去乙酰化酶和热休克蛋白110kDa双靶点抑制剂及应用。本发明提供了式(I)所示结构的一类结构新颖的组蛋白去乙酰化酶和热休克蛋白110kDa双靶点抑制剂、含有式(I)化合物的药物组合物及水合物，以及这些化合物的同位素衍生物、手性异构体、变构体、不同的盐、前药和制剂等。本发明还提供了所述一类结构新颖的组蛋白去乙酰化酶和热休克蛋白110kDa双靶点抑制剂的制备方法、用途，以及这些化合物对结肠癌肿瘤细胞株增殖抑制的活性。本发明中的一类结构新颖的组蛋白去乙酰化酶和热休克蛋白110kDa双靶点抑制剂有望成为抗肿瘤候选药物。#imgabs0#