(2E)-N-(3-chlorophenyl)-3-(4-hydroxyphenyl)prop-2-enamide | 109496-79-9

• 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: (2E)-N-(3-chlorophenyl)-3-(4-hydroxyphenyl)prop-2-enamide
• 英文别名: (E)-N-(3-chlorophenyl)-3-(4-hydroxyphenyl)-prop-2-enamide；4-hydroxy-trans-cinnamic acid-(3-chloro-anilide)；4-Hydroxy-trans-zimtsaeure-(3-chlor-anilid)；(E)-N-(3-chlorophenyl)-3-(4-hydroxyphenyl)prop-2-enamide
• CAS: 109496-79-9
• 化学式: C₁₅H₁₂ClNO₂
• 分子量: 273.719
• InChiKey: KZKTWYPRMCPYNI-RMKNXTFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  反式-4-乙酰氧基肉桂酸 在 草酰氯 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.08h， 生成 (2E)-N-(3-chlorophenyl)-3-(4-hydroxyphenyl)prop-2-enamide
  参考文献：
  名称：

  Monoamine oxidase inhibition by selected anilide derivatives

  摘要：

  A series of anilide derivatives were synthesized and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The most potent inhibitors among the derivatives that were initially evaluated were (2E)-N-(3-chlorophenyl)-3-phenylprop-2-enamide (2c) and (2E)-N-(3-bromophenyl)-3-phenylprop-2-enamide (2d) with IC50 values of 0.53 mu M and 0.45 mu M, respectively. These derivatives exhibited reversible and selective inhibition of MAO-B with binding affinities 37 fold higher for MAO-B than for MAO-A. Analysis of the possible binding interactions of these inhibitors with active site models of human MAO-A and B led to the design of phenolic and benzonitrile derivatives of 2c and 2d. Among these were (2E)-N-(3-chlorophenyl)-3-(4-hydroxyphenyl)prop-2-enamide (7c) and (2E)-N-(3-bromophenyl)-3-(4-hydroxyphenyl)prop-2-enamide (7d) which inhibited MAO-B selectively and reversibly with IC50 values of 0.032 mu M and 0.026 mu M, respectively. These inhibitors were at least 14 fold more potent than 2c and 2d. This study concludes that N,3-diphenylprop-2-enamide is a suitable scaffold for the design of selective MAO-B inhibitors and structural modifications to enhance the binding affinities of the inhibitors for the MAO-B active site include substitution with halogens on the N-phenyl ring and substitution with hydroxyl and nitrile functional groups on the para and meta positions, respectively, of the C3 phenyl ring. Possible binding modes of these structures within the MAO-B active site are proposed with the emphasis on the interactions of the inhibitor halogens and the hydroxyl and nitrile functional groups with active site residues and water molecules. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.08.036

文献信息

• Cinnamic Anilides as New Mitochondrial Permeability Transition Pore Inhibitors Endowed with Ischemia-Reperfusion Injury Protective Effect in Vivo
  作者：Daniele Fancelli、Agnese Abate、Raffaella Amici、Paolo Bernardi、Marco Ballarini、Anna Cappa、Giacomo Carenzi、Andrea Colombo、Cristina Contursi、Fabio Di Lisa、Giulio Dondio、Stefania Gagliardi、Eva Milanesi、Saverio Minucci、Gilles Pain、Pier Giuseppe Pelicci、Alessandra Saccani、Mariangela Storto、Florian Thaler、Mario Varasi、Manuela Villa、Simon Plyte

  DOI：10.1021/jm500547c

  日期：2014.6.26

  In this account, we report the development of a series of substituted cinnamic anilides that represents a novel class of mitochondrial permeability transition pore (mPTP) inhibitors. Initial class expansion led to the establishment of the basic structural requirements for activity and to the identification of derivatives with inhibitory potency higher than that of the standard inhibitor cyclosporine-A

  在这个帐户中，我们报告了一系列取代的肉桂酸苯胺的开发，这些肉桂酸代表了一类新型的线粒体通透性过渡孔（mPTP）抑制剂。最初的类别扩展导致建立了活性的基本结构要求，并鉴定了具有比标准抑制剂环孢菌素-A（CsA）更高的抑制能力的衍生物。这些化合物可响应多种刺激（包括钙超载，氧化应激和硫醇交联剂）抑制mPTP的开放。肉桂酸苯胺类mPTP抑制剂的活性被证明与CsA的活性相加，提示这些抑制剂的分子靶标不同于环绿素D。给出了（E）-3-（4-氟-3-羟基-苯基）-的体外和体内数据N-萘-1-基丙烯酰胺22是该系列中最引人关注的化合物之一，能够减轻mPTP的开放度并限制兔子在急性心肌梗塞模型中的再灌注损伤。
• Monoamine oxidase inhibition by selected anilide derivatives
  作者：Lesetja Legoabe、Johann Kruger、Anél Petzer、Jacobus J. Bergh、Jacobus P. Petzer

  DOI：10.1016/j.ejmech.2011.08.036

  日期：2011.10

  A series of anilide derivatives were synthesized and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The most potent inhibitors among the derivatives that were initially evaluated were (2E)-N-(3-chlorophenyl)-3-phenylprop-2-enamide (2c) and (2E)-N-(3-bromophenyl)-3-phenylprop-2-enamide (2d) with IC50 values of 0.53 mu M and 0.45 mu M, respectively. These derivatives exhibited reversible and selective inhibition of MAO-B with binding affinities 37 fold higher for MAO-B than for MAO-A. Analysis of the possible binding interactions of these inhibitors with active site models of human MAO-A and B led to the design of phenolic and benzonitrile derivatives of 2c and 2d. Among these were (2E)-N-(3-chlorophenyl)-3-(4-hydroxyphenyl)prop-2-enamide (7c) and (2E)-N-(3-bromophenyl)-3-(4-hydroxyphenyl)prop-2-enamide (7d) which inhibited MAO-B selectively and reversibly with IC50 values of 0.032 mu M and 0.026 mu M, respectively. These inhibitors were at least 14 fold more potent than 2c and 2d. This study concludes that N,3-diphenylprop-2-enamide is a suitable scaffold for the design of selective MAO-B inhibitors and structural modifications to enhance the binding affinities of the inhibitors for the MAO-B active site include substitution with halogens on the N-phenyl ring and substitution with hydroxyl and nitrile functional groups on the para and meta positions, respectively, of the C3 phenyl ring. Possible binding modes of these structures within the MAO-B active site are proposed with the emphasis on the interactions of the inhibitor halogens and the hydroxyl and nitrile functional groups with active site residues and water molecules. (C) 2011 Elsevier Masson SAS. All rights reserved.