(E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-methylpiperazin-1-yl)prop-2-en-1-one

• 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)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-methylpiperazin-1-yl)prop-2-en-1-one
• 化学式: C₁₅H₂₀N₂O₃
• 分子量: 276.335
• InChiKey: BCHSTKFDUXIRGF-GQCTYLIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  53
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-methylpiperazin-1-yl)prop-2-en-1-one 、 (2S)-N-[4-(3-bromopropoxy)-5-methoxy-2-nitrobenzoyl]pyrrolidine-2-carboxaldehyde diethyl thioacetal 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 48.0h， 以68%的产率得到(S,E)-3-(4-(3-(4-(2-(bis(ethylthio)methyl)pyrrolidine-1-carbonyl)-2-methoxy-5-nitrophenoxy)propoxy)-3-methoxyphenyl)-1-(4-methylpiperazin-1-yl)prop-2-en-1-one
  参考文献：
  名称：

  [EN] CINNAMIDO-PVRROLOR[2,1-C][1,4]BENZODIAZEPINES AS POTENTIAL ANTICANCER AGENTS AND PROCESS FOR THE PREPARATION THEREOF
  [FR] CINNAMIDO-PVRROLOR[2,1-C][1,4]BENZODIAZÉPINES UTILIÉES COMME AGENTS ANTICANCÉREUX POTENTIELS ET PROCESSUS DE PRÉPARATION DE CES COMPOSÉS

  摘要：

  本发明提供了一种通用公式（8a-i）、（11a-i）、（14a-i）和（17a-i）的化合物，可作为潜在的抗人类癌细胞系肿瘤药物。本发明还提供了一种制备通用公式（8a-i）、（11a-i）、（14a-i）和（17a-i）的桂皮基吡咯并[2,1-c][1,4]苯二氮杂环丙烷的方法。

  公开号：

  WO2010052732A1
• 作为产物：
  描述：

  (E)-3-(4-(苄氧基)-3-甲氧基苯基)丙烯酸乙酯 在 N-甲基吗啉 、 盐酸 、 溶剂黄146 、 sodium hydroxide 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 73.17h， 生成 (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-methylpiperazin-1-yl)prop-2-en-1-one
  参考文献：
  名称：

  Tyrosinase inhibition and anti-melanin generation effect of cinnamamide analogues

  摘要：

  Abnormal melanogenesis results in excessive production of melanin, leading to pigmentation disorders. As a key and rate-limiting enzyme for melanogenesis, tyrosinase has been considered an important target for developing therapeutic agents of pigment disorders. Despite having an (E)-beta-phenyl-alpha,beta-unsaturated carbonyl scaffold, which plays an important role in the potent inhibition of tyrosinase activity, cinnamic acids have not attracted attention as potential tyrosinase inhibitors, due to their low tyrosinase inhibitory activity and relatively high hydrophilicity. Given that cinnamic acids' structure intrinsically features this (E)-scaffold and following our experience that minute changes in the chemical structure can powerfully affect tyrosinase activity, twenty less hydrophilic cinnamamide derivatives were designed as potential tyrosinase inhibitors and synthesised using a Horner-Wadsworth-Emmons reaction. Four of these cinnmamides (4, 9, 14, and 19) exhibited much stronger mushroom tyrosinase inhibition (over 90% inhibition) at 25 mu M compared to kojic acid (20.57% inhibition); crucially, all four have a 2,4-dihydroxy group on the beta-phenyl ring of the scaffold. A docking simulation using tyrosinase indicated that the four cinnamamides exceeded the binding affinity of kojic acid, and bound more strongly to the active site of tyrosinase. Based on the strength of their tyrosinase inhibition, these four cinnamamides were further evaluated in B16F10 melanoma cells. All four cinnamamides, without cytotoxicity, exhibited higher tyrosinase inhibitory activity (67.33 - 79.67% inhibition) at 25 mu M than kojic acid (38.11% inhibition), with the following increasing inhibitory order: morpholino (9) = cyclopentylamino (14) < cyclohexylamino (19) < N-methylpiperazino (4) cinnamamides. Analysis of tyrosinase activity and melanin content in B16F10 cells showed that the four cinnamamides dose-dependently inhibited both cellular tyrosinase activity and melanin content and that their inhibitory activity at 25 mu M was much better than that of kojic acid. The results of melanin content analysis well matched those of the cellular tyrosinase activity analysis, indicating that tyrosinase inhibition by the four cinnamamides is a major factor in the reduction of melanin production. These results imply that these four cinnamamides with a 2,4-dihydroxyphenyl group can act as excellent anti-melanogenic agents in the treatment of pigmentation disorders.

  DOI：

  10.1016/j.bioorg.2019.03.001

文献信息

• Bioassay of ferulic acid derivatives as influenza neuraminidase inhibitors
  作者：Man‐Ying Cui、Meng‐Wu Xiao、Lv‐Jie Xu、Yun Chen、Ai‐Lin Liu、Jiao Ye、Ai‐Xi Hu

  DOI：10.1002/ardp.201900174

  日期：2020.1

  respectively. On the basis of the biological results, a preliminary structure–activity relationship (SAR) was derived and discussed. Besides, molecular docking was performed to study the possible interactions of compounds 1p, 2d, 3b, and 4a with the active site of NA. It was found that the 4‐OH‐3‐OMe group and the amide group (CON) of ferulic acid amide derivatives were two key pharmacophores for NA

  设计、合成了四个系列的阿魏酸衍生物，并评估了它们在体外对 H1N1 流感病毒的神经氨酸酶 (NA) 抑制活性。药理结果表明，大多数目标化合物表现出中等的流感NA抑制活性，也优于阿魏酸。两种最有效的化合物是 1m 和 4a，IC50 值分别为 12.77 ± 0.47 和 12.96 ± 1.34 μg/ml。在生物学结果的基础上，推导出并讨论了初步的构效关系（SAR）。此外，还进行了分子对接以研究化合物 1p、2d、3b 和 4a 与 NA 活性位点的可能相互作用。发现阿魏酸酰胺衍生物的 4-OH-3-OMe 基团和酰胺基团 (CON) 是 NA 抑制活性的两个关键药效团。进一步修饰天然产物阿魏酸以提高其对流感NA的抑制活性具有重要意义。
• CINNAMIDO-PYRROLO[2,1-C][1,4]BENZODIAZEPINES AS POTENTIAL ANTICANCER AGENTS AND PROCESS FOR THE PREPARATION THEREOF
  申请人：Ahmed Kamal

  公开号：US20120095213A1

  公开（公告）日：2012-04-19

  The present invention provides a compound of general formulae (8a-i), (11a-i), (14a-i), and (17a-i), useful as potential antitumour agents against human cancer cell lines. The present invention further provides a process for the preparation of Cinnamido-pyrrolo[2,1-c][1,4]benzodiazepines of general formulae (8a-i), (11a-i), (14a-i), and (17a-i).
• US8722665B2
  申请人：——

  公开号：US8722665B2

  公开（公告）日：2014-05-13
• Tyrosinase inhibition and anti-melanin generation effect of cinnamamide analogues
  作者：Sultan Ullah、Chaeun Park、Muhammad Ikram、Dongwan Kang、Sanggwon Lee、Jungho Yang、Yujin Park、Sik Yoon、Pusoon Chun、Hyung Ryong Moon

  DOI：10.1016/j.bioorg.2019.03.001

  日期：2019.6

  Abnormal melanogenesis results in excessive production of melanin, leading to pigmentation disorders. As a key and rate-limiting enzyme for melanogenesis, tyrosinase has been considered an important target for developing therapeutic agents of pigment disorders. Despite having an (E)-beta-phenyl-alpha,beta-unsaturated carbonyl scaffold, which plays an important role in the potent inhibition of tyrosinase activity, cinnamic acids have not attracted attention as potential tyrosinase inhibitors, due to their low tyrosinase inhibitory activity and relatively high hydrophilicity. Given that cinnamic acids' structure intrinsically features this (E)-scaffold and following our experience that minute changes in the chemical structure can powerfully affect tyrosinase activity, twenty less hydrophilic cinnamamide derivatives were designed as potential tyrosinase inhibitors and synthesised using a Horner-Wadsworth-Emmons reaction. Four of these cinnmamides (4, 9, 14, and 19) exhibited much stronger mushroom tyrosinase inhibition (over 90% inhibition) at 25 mu M compared to kojic acid (20.57% inhibition); crucially, all four have a 2,4-dihydroxy group on the beta-phenyl ring of the scaffold. A docking simulation using tyrosinase indicated that the four cinnamamides exceeded the binding affinity of kojic acid, and bound more strongly to the active site of tyrosinase. Based on the strength of their tyrosinase inhibition, these four cinnamamides were further evaluated in B16F10 melanoma cells. All four cinnamamides, without cytotoxicity, exhibited higher tyrosinase inhibitory activity (67.33 - 79.67% inhibition) at 25 mu M than kojic acid (38.11% inhibition), with the following increasing inhibitory order: morpholino (9) = cyclopentylamino (14) < cyclohexylamino (19) < N-methylpiperazino (4) cinnamamides. Analysis of tyrosinase activity and melanin content in B16F10 cells showed that the four cinnamamides dose-dependently inhibited both cellular tyrosinase activity and melanin content and that their inhibitory activity at 25 mu M was much better than that of kojic acid. The results of melanin content analysis well matched those of the cellular tyrosinase activity analysis, indicating that tyrosinase inhibition by the four cinnamamides is a major factor in the reduction of melanin production. These results imply that these four cinnamamides with a 2,4-dihydroxyphenyl group can act as excellent anti-melanogenic agents in the treatment of pigmentation disorders.
• [EN] CINNAMIDO-PVRROLOR[2,1-C][1,4]BENZODIAZEPINES AS POTENTIAL ANTICANCER AGENTS AND PROCESS FOR THE PREPARATION THEREOF<br/>[FR] CINNAMIDO-PVRROLOR[2,1-C][1,4]BENZODIAZÉPINES UTILIÉES COMME AGENTS ANTICANCÉREUX POTENTIELS ET PROCESSUS DE PRÉPARATION DE CES COMPOSÉS
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2010052732A1

  公开（公告）日：2010-05-14

  The present invention provides a compound of general formulae (8a-i), (11a-i), (14a-i), and (17a-i), useful as potential antitumour agents against human cancer cell lines. The present invention further provides a process for the preparation of Cinnamido-pyrrolo[2,1-c][1,4]benzodiazepines of general formulae (8a-i), (11a-i), (14a-i), and (17a-i).

  本发明提供了一种通用公式（8a-i）、（11a-i）、（14a-i）和（17a-i）的化合物，可作为潜在的抗人类癌细胞系肿瘤药物。本发明还提供了一种制备通用公式（8a-i）、（11a-i）、（14a-i）和（17a-i）的桂皮基吡咯并[2,1-c][1,4]苯二氮杂环丙烷的方法。