(E)-3-(4-(4-methylpiperazin-1-yl)phenyl)acrylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (E)-3-(4-(4-methylpiperazin-1-yl)phenyl)acrylic acid
• 英文别名: (E)-3-[4-(4-methylpiperazin-4-ium-1-yl)phenyl]prop-2-enoate
• 化学式: C₁₄H₁₈N₂O₂
• mdl: MFCD06205587
• 分子量: 246.309
• InChiKey: CZAFCRAXLSUYPN-QPJJXVBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.357
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-甲基哌嗪 在 哌啶 、 吡啶 、 Aliquat (at)366 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 (E)-3-(4-(4-methylpiperazin-1-yl)phenyl)acrylic acid
  参考文献：
  名称：

  Design, synthesis, 3D pharmacophore, QSAR, and docking studies of carboxylic acid derivatives as Histone Deacetylase inhibitors and cytotoxic agents

  摘要：

  In this study, five series of (E)-6-(4-substituted phenyl)-4-oxohex-5-enoic acids IIb-f (E), (E)-3-(4-(substituted)-phenyl) acrylic acids IIIa-g (E), 4-(4-(substituted) phenylamino)-4-oxobutanoic acids VIa,b,e, 5-(4-(substituted) phenylamino)-5-oxopentanoic acids VIIa,f and 2-[(4-(substituted) phenyl) carbamoyl] benzoic acids VIIIa,e were designed and synthesized. Selected compounds were screened in vitro for their cytotoxic effect on 60 human NCI tumor cell lines. Compound IIf (E) displayed significant inhibitory activity against NCI Non-Small Cell Lung A549/ATCC Cancer cell line (68% inhibition) and NCI-H460 Cancer cell line (66% inhibition). Moreover, the final compounds were evaluated in vitro for their cytotoxic activity on HepG2 Cancer cell line in which histone deacetylase (HDAC) is overexpressed. Compounds IIc (E), IIf (E), IIIb (E), and IIIg (E) exhibited the highest cytotoxic activity against HepG2 human cancer cell lines with IC50 ranging from 2.27 to 10.71 mu M. In addition, selected compounds were tested on histone deacetylase isoforms (HDAC1-11). Molecular docking simulation was also carried out for HDLP enzyme to investigate their HDAC binding affinity. In addition, generation of 3D-pharmacophore model and quantitative structure activity relationship (QSAR) models were combined to explore the structural requirements controlling the observed cytotoxic properties. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2014.08.006

文献信息

• CARBOLINE DERIVATIVES
  申请人：ICOS CORPORATION

  公开号：EP0912567B1

  公开（公告）日：2002-04-10
• US6043252A
  申请人：——

  公开号：US6043252A

  公开（公告）日：2000-03-28
• US6117881A
  申请人：——

  公开号：US6117881A

  公开（公告）日：2000-09-12
• US6306870B1
  申请人：——

  公开号：US6306870B1

  公开（公告）日：2001-10-23
• Design, synthesis, 3D pharmacophore, QSAR, and docking studies of carboxylic acid derivatives as Histone Deacetylase inhibitors and cytotoxic agents
  作者：Mona M. Abdel-Atty、Nahla A. Farag、Shaymaa E. Kassab、Rabah A.T. Serya、Khaled A.M. Abouzid

  DOI：10.1016/j.bioorg.2014.08.006

  日期：2014.12

  In this study, five series of (E)-6-(4-substituted phenyl)-4-oxohex-5-enoic acids IIb-f (E), (E)-3-(4-(substituted)-phenyl) acrylic acids IIIa-g (E), 4-(4-(substituted) phenylamino)-4-oxobutanoic acids VIa,b,e, 5-(4-(substituted) phenylamino)-5-oxopentanoic acids VIIa,f and 2-[(4-(substituted) phenyl) carbamoyl] benzoic acids VIIIa,e were designed and synthesized. Selected compounds were screened in vitro for their cytotoxic effect on 60 human NCI tumor cell lines. Compound IIf (E) displayed significant inhibitory activity against NCI Non-Small Cell Lung A549/ATCC Cancer cell line (68% inhibition) and NCI-H460 Cancer cell line (66% inhibition). Moreover, the final compounds were evaluated in vitro for their cytotoxic activity on HepG2 Cancer cell line in which histone deacetylase (HDAC) is overexpressed. Compounds IIc (E), IIf (E), IIIb (E), and IIIg (E) exhibited the highest cytotoxic activity against HepG2 human cancer cell lines with IC50 ranging from 2.27 to 10.71 mu M. In addition, selected compounds were tested on histone deacetylase isoforms (HDAC1-11). Molecular docking simulation was also carried out for HDLP enzyme to investigate their HDAC binding affinity. In addition, generation of 3D-pharmacophore model and quantitative structure activity relationship (QSAR) models were combined to explore the structural requirements controlling the observed cytotoxic properties. (C) 2014 Elsevier Inc. All rights reserved.