N-(2-amino-phenyl)-4-(butyrylamino-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-(butyrylamino-methyl)benzamide
• 英文别名: N-(2-aminophenyl)-4-(butyrylaminomethyl)benzamide；N-(2-aminophenyl)-4-[(butanoylamino)methyl]benzamide
• 化学式: C₁₈H₂₁N₃O₂
• 分子量: 311.384
• InChiKey: JNZVVBSYCDVBHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 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)butyramide 在 palladium on activated charcoal 氢气 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 生成 N-(2-amino-phenyl)-4-(butyrylamino-methyl)benzamide
  参考文献：
  名称：

  Zn²⁺-Chelating Motif-Tethered Short-Chain Fatty Acids as a Novel Class of Histone Deacetylase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm0303655

文献信息

• [EN] ARYLENE-CARBOXYLIC ACID (2-AMINO-PHENYL)-AMIDE DERIVATIVES AS PHARMACEUTICAL AGENTS<br/>[FR] DERIVES DE (2-AMINO-PHENYL)-AMIDE D'ACIDE ARYLENE-CARBOXYLIQUE SERVANT D'AGENTS PHARMACEUTIQUES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2004052838A1

  公开（公告）日：2004-06-24

  The present invention describes compounds of general formula (I), a process for their manufacture, medicaments containing them and their manufacture as well as the use of these compounds as pharmaceutical agents. The compounds according to this invention show antiproliferative and differentiation- inducing activity, which results in inhibition of tumor cell proliferation, induction of apoptosis and inhibition of invasion.

  本发明描述了一般式(I)的化合物，其制备方法，含有这些化合物的药物及其制备方法，以及将这些化合物用作药用剂的用途。根据本发明的化合物显示出抗增殖和诱导分化活性，导致抑制肿瘤细胞增殖，诱导凋亡和抑制侵袭。
• Novel arylene-carboxylic acid (2-amino-phenyl)-amide derivatives
  申请人：——

  公开号：US20040138270A1

  公开（公告）日：2004-07-15

  The present invention describes compounds of the general formula I 1 as well as processes for their manufacture, pharmaceutical compositions containing them and methods for using these compounds and pharmaceutical compositions as pharmaceutical agents. The compounds according to this invention show antiproliferative and differentiation-inducing activity, which results in inhibition of tumor cell proliferation, induction of apoptosis and inhibition of invasion.

  本发明描述了一般式I1的化合物，以及制造它们的过程，包含它们的药物组合物以及将这些化合物和药物组合物用作药物制剂的方法。根据本发明的化合物表现出抗增殖和诱导分化的活性，这导致抑制肿瘤细胞增殖、诱导凋亡和抑制侵袭。
• 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。
• ARYLENE-CARBOXYLIC ACID (2-AMINO-PHENYL)-AMIDE DERIVATIVES AS PHARMACEUTICAL AGENTS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1572625A1

  公开（公告）日：2005-09-14