3-[4-(2-propylpentanoyl)phenyl]acrylic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 3-[4-(2-propylpentanoyl)phenyl]acrylic acid
• 英文别名: (E)-3-[4-(2-propylpentanoylamino)phenyl]prop-2-enoic acid
• 化学式: C₁₇H₂₃NO₃
• 分子量: 289.375
• InChiKey: YZYCBPWJWDAOKG-FMIVXFBMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-[4-(2-propylpentanoyl)phenyl]acrylic acid 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 TEA 、 盐酸羟胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 以40%的产率得到N-hydroxy-3-[4-(2-propyl-pentanoylamino)phenyl]acrylamide
  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
• 作为产物：
  描述：

  (2E)-3-(4-氨基苯基)-2-丙烯酸 在 氢氧化钾 、 三甲基氯硅烷 、 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 1.0h， 生成 3-[4-(2-propylpentanoyl)phenyl]acrylic acid
  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

• 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。
• 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
• US8318808B2
  申请人：——

  公开号：US8318808B2

  公开（公告）日：2012-11-27