N-(2-amino-phenyl)-4-(phenylacetylamino-methyl)benzamide

• 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-amino-phenyl)-4-(phenylacetylamino-methyl)benzamide
• 英文别名: N-(2-aminophenyl)-4-[[(2-phenylacetyl)amino]methyl]benzamide
• 化学式: C₂₂H₂₁N₃O₂
• 分子量: 359.428
• InChiKey: JRFBVLJXBBJSFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  84.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-(4-Carboxybenzyl)phenylacetamide 在 氯化亚砜 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 N-(2-amino-phenyl)-4-(phenylacetylamino-methyl)benzamide
  参考文献：
  名称：

  借助计算机设计策略开发新的 HDAC1-3 酶抑制剂

  摘要：

  组蛋白去乙酰化酶 (HDAC) 在癌症中过度表达，它们的抑制在癌症治疗中显示出有希望的结果。特别是，选择性 I 类 HDAC 抑制剂如恩替司他被认为在乳腺癌治疗中更有益。计算药物设计是当今药物发现项目中不可避免的一部分，因为它在节省时间和成本方面具有明确的作用。使用三种 HDAC 抑制剂曲古抑菌素、伏立诺他和恩替司他作为模板结构和多样化的片段库，其所有可合成的化合物 (~3200) 都是虚拟生成的，并基于与模板的相似性和 PAINS 去除进行过滤。选择的 298 个结构与 HDAC I 的活性位点对接，并使用计算的结合亲和力进行排序。顶级结构是人工检查的，并且，考虑到合成的容易性和药物相似性，提出了两种新的结构（3a 和 3b）用于合成和生物学评价。合成的化合物被纯化到超过 95% 的程度，并使用各种方法进行结构验证。设计的化合物 3a 和 3b 分别在 10 μM 浓度下对 HDAC 1、2

  DOI：

  10.1021/acs.jcim.1c01557

文献信息

• Zn2Motif-Tethered Short-Chain Fatty Acids as a Novel Class of Histone Deacetylase
  申请人：Chen Ching-Shih

  公开号：US20070225373A1

  公开（公告）日：2007-09-27

  Zn 2+ -chelating motif-tethered fatty acids as histone deacetylase (HDAC) inhibitors. One hydroxamate-tethered phenylbutyrate compound, N-hydroxy-4-(4-phenylbutyrylamino)-benzamide (HTPB), displayed nM potency in inhibiting HDAC activity. Exposure of several cancer cell lines to HTPB at sub-μM concentrations showed reduced cell proliferation accompanied by histone hyperacetylation and elevated p21 WAF/CIP1 expression, hallmark features associated with intracellular HDAC inhibition.

  Zn2+螯合基固定的脂肪酸作为组蛋白去乙酰化酶（HDAC）抑制剂。一种羟酰胺基固定的苯丁酸化合物，N-羟基-4-(4-苯丁酰氨基)-苯甲酰胺（HTPB），在抑制HDAC活性方面表现出纳摩尔级别的效力。将几种癌细胞系暴露于亚微米浓度的HTPB中，显示出细胞增殖减少，伴随着组蛋白高乙酰化和升高的p21WAF/CIP1表达，这是与细胞内HDAC抑制相关的标志性特征。
• ZN2+Chelating Motif-Tethered Short-Chain Fatty Acids as a Novel Class of Histone Deacetylase Inhibitors
  申请人：Chen Ching-Shih

  公开号：US20090137679A1

  公开（公告）日：2009-05-28

  Zn 2+ -chelating motif-tethered fatty acids as histone deacetylase (HDAC) inhibitors. Compounds performed well in in vitro and in vivo tests.

  以Zn2+螯合基固定的脂肪酸作为组蛋白去乙酰化酶（HDAC）抑制剂。该化合物在体外和体内测试中表现良好。
• Zn²⁺-Chelating Motif-Tethered Short-Chain Fatty Acids as a Novel Class of Histone Deacetylase Inhibitors
  作者：Qiang Lu、Ya-Ting Yang、Chang-Shi Chen、Melanie Davis、John C. Byrd、Mark R. Etherton、Asad Umar、Ching-Shih Chen

  DOI：10.1021/jm0303655

  日期：2004.1.1

  Among various classes of histone deacetylase (HDAC) inhibitors, short-chain fatty acids exhibit the least potency, with IC50 in the millimolar range. We rationalized that this weak potency was, in part, attributable to their inability to access the zinc cation in the HDAC active-site pocket, which is pivotal to the deacetylation catalysis. We thus explored the structural optimization of valproate, butyrate, phenylacetate, and phenylbutyrate by coupling them with Zn2+-chelating motifs (hydroxamic acid and o-phenylenediamine) through aromatic W-amino acid linkers. This strategy has led to a novel class of Zn2+ -chelating, motif-tethered, short-chain fatty acids that exhibited varying degrees of HDAC inhibitory potency. One hydroxamate-tethered phenylbutyrate compound, N-hydroxy-4-(4-phenylbutyrylamino)benzamide (HTPB), displayed nanomolar potency in inhibiting HDAC activity. Exposure of several cancer cell lines to HTPB at the submicromolar level showed reduced cell proliferation accompanied by histone hyperacetylation and elevated p21(WAF/CIPI) expression, which are hallmark features associated with intracellular HDAC inhibition.
• ZN 24 -CHELATING MOTIF-TETHERED SHORT-CHAIN FATTY ACIDS AS A NOVEL CLASS OF HISTONE DEACETYLASE INHIBITORS
  申请人：THE OHIO STATE UNIVERSITY RESEARCH FOUNDATION

  公开号：EP1696898A2

  公开（公告）日：2006-09-06
• ZN 2+ -CHELATING MOTIF-TETHERED SHORT-CHAIN FATTY ACIDS AS A NOVEL CLASS OF HISTONE DEACETYLASE INHIBITORS
  申请人：The Ohio State University Research Foundation

  公开号：EP1696898B1

  公开（公告）日：2015-11-18