(E)-N-benzyl-3-(4-hydroxyphenyl)acrylamide

• 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: (E)-N-benzyl-3-(4-hydroxyphenyl)acrylamide
• 英文别名: (E)-N-benzyl-3-(4-hydroxyphenyl)prop-2-enamide
• 化学式: C₁₆H₁₅NO₂
• 分子量: 253.301
• InChiKey: QQDGGVVFYXVOQK-DHZHZOJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.062
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-胍基苯甲酸甲烷磺酸盐 、 (E)-N-benzyl-3-(4-hydroxyphenyl)acrylamide 在 N,N'-二环己基碳二亚胺 作用下， 以 吡啶 为溶剂， 以48%的产率得到[4-[4-[(E)-3-(benzylamino)-3-oxoprop-1-enyl]phenoxy]carbonylphenyl]-(diaminomethylidene)azanium;methanesulfonate
  参考文献：
  名称：

  Synthesis and structure-activity relationship study of the new set of trypsin-like proteinase inhibitors

  摘要：

  A new set of 25 trypsin-like proteinase inhibitors was prepared and the inhibiting activity on trypsin, thrombin, plasmin and urokinase was measured. The structure-activity relationship is discussed. High inhibiting activities were observed in 4-guanidinobenzoic acid esters only. The replacement of this moiety for N-formamidinyl-isonipecotic acid or an arginine moiety caused almost total loss of the activity. In the series of 4-guanidinobenzoic acid esters, any important influence of the ester-groups reactivity was observed. The trypsin-thrombin selectivity in the compounds with the guanidine-remote carboxylic function was also observed. (C) 1999 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(99)00123-3
• 作为产物：
  描述：

  p-acetoxycinnamoyl chloride 在 四氢吡咯 、 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 (E)-N-benzyl-3-(4-hydroxyphenyl)acrylamide
  参考文献：
  名称：

  Development trans-N-benzyl hydroxyl cinnamamide based compounds from cinnamic acids and characteristics anticancer potency

  摘要：

  三种羟基肉桂酰胺的衍生物成为反式-N-苄基羟基肉桂酰胺，并进行了抗癌剂的潜在检测。N-苄基-对香豆酰胺（5a）、N-苄基咖啡酰胺（5b）和N-苄基阿魏酰胺（5c）分别由对香豆酸、咖啡酸和阿魏酸与苄胺通过四个反应步骤（即乙酰化、氯化、酰胺化和脱乙酰化）获得。所有产品均采用FTIR、1H-NMR和13C-NMR光谱进行表征，并通过MTT法对P388白血病鼠细胞进行细胞毒性测试。虽然化合物5b和5c没有抗癌活性，IC50分别为674.38和179.56 µg/mL，但化合物5a具有潜在的抗癌活性，IC50为16.15 µg/mL。进行了分子建模研究，以了解其与鼠白血病P388细胞活性的相互作用。

  DOI：

  10.1007/s13738-022-02499-7

文献信息

• Synthesis of cinnamic amide derivatives and their anti-melanogenic effect in α-MSH-stimulated B16F10 melanoma cells
  作者：Sultan Ullah、Dongwan Kang、Sanggwon Lee、Muhammad Ikram、Chaeun Park、Yujin Park、Sik Yoon、Pusoon Chun、Hyung Ryong Moon

  DOI：10.1016/j.ejmech.2018.10.025

  日期：2019.1

  debenzylation of cinnamic amides 45–49 with the anilino moiety provided our desired cinnamic amides 6–10 without inducing the intramolecular Michael addition. Debenzylation of cinnamic amides 43, 48, and 53 with a 2,4-dibenzyloxyphenyl group was also successfully accomplished using BBr3 to give 4, 9, and 14. Among the nine compounds that inhibited mushroom tyrosinase more potently at 25 μM than kojic acid, four

  在调节黑色素生物合成的三种酶，酪氨酸酶及其相关蛋白TYRP-1和TYRP-2中，酪氨酸酶是最重要的，因为它能够限制黑色素细胞中黑色素的产生速率。对于治疗由黑色素过量引起的皮肤色素沉着症，酪氨酸酶的抑制是迄今为止最成熟的策略。肉桂酸是一种安全的天然产物，具有（E）-β-苯基-α，β-不饱和羰基，我们先前已证明其在抑制酪氨酸酶中起重要作用。由于肉桂酸相对亲水，这阻碍了它在皮肤上的吸收，因此少了十五种亲水性肉桂酰胺衍生物（1 – 15）被设计为安全且更有效的酪氨酸酶抑制剂，并通过Horner-Wadsworth-Emmons反应合成。使用浓的去苄基化-HCl和乙酸ö苄基-保护的肉桂酰胺40 - 54产生以下三个结果。1）肉桂酰胺类43，48，和53与2,4-组二苄，无论胺类型的酰胺的，产生具有高极性配位化合物。2）肉桂酰胺类40 - 42，44，50 - 52，和54用苄基氨基，或二乙胺基取代产生了所需的脱苄基肉桂酰胺13，5，10
• NOVEL ACETAMIDE DERIVATIVES AND PROTEASE INHIBITORS
  申请人：NIPPON KAYAKU KABUSHIKI KAISHA

  公开号：EP0936216A1

  公开（公告）日：1999-08-18

  The present invention relates to novel acetamide derivatives having a substituted heterocyclic group and consecutive dicarbonyl structures, for example 1-pyrimidinylacetamide compounds, 1-pyrazinylacetamide compounds, 1-triazinylacetamide compounds etc., and these compounds have inhibitory activity on chymotrypsin type proteases and are useful as inhibitors for said enzymes, particularly as chymase inhibitors. The novel acetamide derivatives of the present invention are shown in formula (I) below: wherein R0 is substituted or unsubstituted phenyl; R1 is aryl, heteroaryl or aliphatic lower alkyl which may be substituted or unsubstituted; R2 is substituted or unsustituted alkyl, arylalkyl, or heteroarylalkyl; R3 is hydrogen; acyl group; sulfonyl group; isocyanate group; thiourea; or hydrogen, a lower alkyl or a substituted lower alkyl; aryl (1-7C) alkyl, heteroaryl (1-7C) alkyl, aryl and heteroaryl; X and Y independently represent a nitrogen atom or a carbon atom; and Z is a polymethylene group wherein a hydrogen atom in the polymethylene may be replaced.

  本发明涉及具有取代杂环基团和连续二羰基结构的新型乙酰胺衍生物，例如1-嘧啶基乙酰胺化合物、1-吡嗪基乙酰胺化合物、1-三嗪基乙酰胺化合物等，这些化合物对糜蛋白酶型蛋白酶具有抑制活性，可用作上述酶的抑制剂，特别是糜蛋白酶抑制剂。本发明的新型乙酰胺衍生物如下式(I)所示： 其中 R0 是取代或未取代的苯基；R1 是芳基、杂芳基或可取代或未取代的脂肪族低级烷基；R2 是取代或未取代的烷基、芳烷基或杂芳基；R3 是氢；酰基；磺酰基；异氰酸酯基；硫脲；或氢、低级烷基或取代的低级烷基；芳基（1-7C）烷基、杂芳基（1-7C）烷基、芳基和杂芳基； X 和 Y 独立地代表一个氮原子或一个碳原子；Z 是一个聚亚甲基，其中聚亚甲基中的一个氢原子可被取代。
• Synthesis and structure-activity relationship study of the new set of trypsin-like proteinase inhibitors
  作者：Pavol Zlatoidsky、Tibor Maliar

  DOI：10.1016/s0223-5234(99)00123-3

  日期：1999.12

  A new set of 25 trypsin-like proteinase inhibitors was prepared and the inhibiting activity on trypsin, thrombin, plasmin and urokinase was measured. The structure-activity relationship is discussed. High inhibiting activities were observed in 4-guanidinobenzoic acid esters only. The replacement of this moiety for N-formamidinyl-isonipecotic acid or an arginine moiety caused almost total loss of the activity. In the series of 4-guanidinobenzoic acid esters, any important influence of the ester-groups reactivity was observed. The trypsin-thrombin selectivity in the compounds with the guanidine-remote carboxylic function was also observed. (C) 1999 Editions scientifiques et medicales Elsevier SAS.
• Development trans-N-benzyl hydroxyl cinnamamide based compounds from cinnamic acids and characteristics anticancer potency
  作者：Firdaus Zenta、Nunuk Hariani Soekamto、Seniwati Dali、Syadza Firdausiah、Herlina Rasyid、Bahriah Bahriah、Agustan Agustan、Dahlang Tahir

  DOI：10.1007/s13738-022-02499-7

  日期：2022.7

  The derivatization of three hydroxycinnamamides becomes trans-N-benzylhydroxycinnamamides, and their potential assay as anticancer agents has been carried out. N-benzyl-p-coumaramide (5a), N-benzylcaffeamide (5b), and N-benzylferulamide (5c) were obtained from p-coumaric, caffeic, and ferulic acid, respectively, with benzylamine via four reaction steps, i.e., acetylation, chlorination, amidation, and deacetylation. All products characterize using FTIR, 1H-NMR, and 13C-NMR spectroscopy, and their cytotoxicity were tested against P388 leukemia murine cells by MTT method. Although compound 5b and 5c have no and low anticancer activity with IC50 sequentially of 674.38 and 179.56 µg/mL, compound 5a showed potentially use as an anticancer agent with IC50 of 16.15 µg/mL Molecular modelling studies were performed to understand the interactions with the activity against murine leukemia P388 cells.

  三种羟基肉桂酰胺的衍生物成为反式-N-苄基羟基肉桂酰胺，并进行了抗癌剂的潜在检测。N-苄基-对香豆酰胺（5a）、N-苄基咖啡酰胺（5b）和N-苄基阿魏酰胺（5c）分别由对香豆酸、咖啡酸和阿魏酸与苄胺通过四个反应步骤（即乙酰化、氯化、酰胺化和脱乙酰化）获得。所有产品均采用FTIR、1H-NMR和13C-NMR光谱进行表征，并通过MTT法对P388白血病鼠细胞进行细胞毒性测试。虽然化合物5b和5c没有抗癌活性，IC50分别为674.38和179.56 µg/mL，但化合物5a具有潜在的抗癌活性，IC50为16.15 µg/mL。进行了分子建模研究，以了解其与鼠白血病P388细胞活性的相互作用。