(E)-3-(4-hydroxyphenyl)-1-morpholinoprop-2-en-1-one | 21497-16-5

• 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-hydroxyphenyl)-1-morpholinoprop-2-en-1-one
• 英文别名: 4-[3-(4-hydroxy-phenyl)-acryloyl]-morpholine；trans-p-Hydroxy-zimtsaeuremorpholid；(E)-3-(4-hydroxyphenyl)-1-morpholin-4-ylprop-2-en-1-one
• CAS: 21497-16-5
• 化学式: C₁₃H₁₅NO₃
• 分子量: 233.267
• InChiKey: AHAPXCANEJCINV-ZZXKWVIFSA-N

物化性质

• 沸点：
  471.5±45.0 °C(Predicted)
• 密度：
  1.246±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-3-(4-hydroxyphenyl)-1-morpholinoprop-2-en-1-one 、 4-胍基苯甲酸甲烷磺酸盐 在 N,N'-二环己基碳二亚胺 作用下， 以 吡啶 为溶剂， 以38%的产率得到diaminomethylidene-[4-[4-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]phenoxy]carbonylphenyl]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：

  乙基 3-[4-(苄氧基)苯基]丙烯酸酯 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-hydroxyphenyl)-1-morpholinoprop-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

• Some condensation reactions between aromatic aldehydes and 1,1-bisdialkylaminoalkenes and related compounds
  作者：D. H. R. Barton、G. Hewitt、P. G. Sammes

  DOI：10.1039/j39690000016

  日期：——

  Condensation of 1,1-bisdialkylaminoethenes with aromatic aldehydes gives the corresponding trans-cinnamoyl amides in fair yield. Salicylaldehyde affords coumarin. 1,1-Bisdialkylamino-1,3-dienes and aromatic aldehydes produce 5-arylpenta-cis-2,trans-4-dienoyl dialkylamides. The mechanisms of these reactions have been explored. Some related condensations using 1-alkoxy-1-dialkylaminoethenes and 1-al

  1，1-双二烷基氨基乙烯与芳族醛的缩合以适当的收率得到相应的反式肉桂酰基酰胺。水杨醛提供香豆素。1，1-双二烷基氨基-1，3-二烯和芳族醛产生5-芳基五-顺-2，反式-4-二壬基二烷基酰胺。已经研究了这些反应的机理。还研究了一些使用1-烷氧基-1-二烷基氨基乙烯和1-烷硫基-1-二烷基氨基乙烯的缩合反应。
• 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.
• 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.