4-((Z)-4-fluorobenzylidene)-2-((E)-styryl)oxazol-5(4H)-one

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-((Z)-4-fluorobenzylidene)-2-((E)-styryl)oxazol-5(4H)-one
• 英文别名: (4Z)-4-[(4-fluorophenyl)methylidene]-2-[(E)-2-phenylethenyl]-1,3-oxazol-5-one
• 化学式: C₁₈H₁₂FNO₂
• 分子量: 293.297
• InChiKey: SUTJVPZHGFNCST-NJAVVXAXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  正丙胺 、 4-((Z)-4-fluorobenzylidene)-2-((E)-styryl)oxazol-5(4H)-one 以 乙醇 为溶剂， 反应 2.0h， 以82%的产率得到(Z)-2-cinnamamido-3-(4-fluorophenyl)-N-propylacrylamide
  参考文献：
  名称：

  Introducing of potent cytotoxic novel 2-(aroylamino)cinnamamide derivatives against colon cancer mediated by dual apoptotic signal activation and oxidative stress

  摘要：

  Curcumin and trans-cinnamaldehyde are acrolein-based Michael acceptor compounds that are commonly found in domestic condiments, and known to cause cancer cell death via redox mechanisms. Based on the structural features of these compounds we designed and synthesized several 2-cinnamamido-N-substituted-cinnamamide (bis-cinnamamide) compounds. One of the derivatives, (Z)-2-[(E)-cinnamamido]-3-phenyl-N-propylacrylamide 8 showed a moderate antiproliferative potency (HCT-116 cell line inhibition of 32.0 mu M), no inhibition of normal cell lines C-166, and proven cellular activities leading to apoptosis. SAR studies led to more than 10-fold increase in activity. Our most promising compound, [(Z)-3-(1H-indol-3-yl)-N-propyl-2-[(E)-3-(thien-2-yl)propenamido) propenamide] 45 killed colon cancer cells at IC50 = 0.89 mu M (Caco-2), 2.85 mu M (HCT-116) and 1.65 mu M (HT -29), while exhibiting much weaker potency on C-166 and BHK normal cell lines (IC50 = 71 mu M and 77.6 mu M, respectively). Cellular studies towards identifying the compounds mechanism of cytotoxic activities revealed that apoptotic induction occurs in part as a result of oxidative stress. Importantly, the compounds showed inhibition of cancer stem cells that are critical for maintaining the potential for self-renewal and stemness. The results presented here show discovery of covalently acting Michael addition compounds that potently kill cancer cells by a defined mechanism, with prominent selectivity profile over non-cancerous cell lines.

  DOI：

  10.1016/j.bioorg.2020.103953
• 作为产物：
  描述：

  3-苯基-2-丙烯酰氯 在 sodium acetate 作用下， 以 乙酸酐 为溶剂， 反应 2.0h， 生成 4-((Z)-4-fluorobenzylidene)-2-((E)-styryl)oxazol-5(4H)-one
  参考文献：
  名称：

  通过Pd介导的Kaede蛋白发色团类似物的光环加成反应合成二氨基truxillic bis-氨基酸的酯。

  摘要：

  据报道，由多官能恶唑酮立体合成合成木耳二氨基酯。4-（（Z）-亚芳基）-2-（E）-styryl-5（4 H）-恶唑酮2与Pd（OAc）2的反应导致邻位pal合并形成双核开卷复合物带有羧酸盐桥的3，其中Pd原子是与恶唑酮键合的C ^ N。在3中，恶唑酮的两个环外C = C键面对面排列，这对于它们的[2 + 2]光环加成是最佳的。在CH 2 Cl 2中辐照二聚体3蓝光（465 nm）的溶液促进了环外C = C键的化学和立体选择[2 + 2]光环加成反应，并形成了含环丁烷的邻钯配合物4。在MeOH / NCMe混合物中用CO处理4促进了钯化的碳的甲氧基羰基化，并释放了作为单一异构体的相应的邻官能化的1，3-二氨基苯甲基双氨基酯5。

  DOI：

  10.3762/bjoc.16.98

文献信息

• Introducing of potent cytotoxic novel 2-(aroylamino)cinnamamide derivatives against colon cancer mediated by dual apoptotic signal activation and oxidative stress
  作者：Abdelsattar M. Omar、Moustafa E. El-Araby、Tamer M. Abdelghany、Martin K. Safo、Mostafa H. Ahmed、Rio Boothello、Bhaumik B Patel、Mohamed S. Abdel-Bakky、Azizah M. Malebari、Hany E.A. Ahmed、Radwan S. Elhaggar

  DOI：10.1016/j.bioorg.2020.103953

  日期：2020.8

  Curcumin and trans-cinnamaldehyde are acrolein-based Michael acceptor compounds that are commonly found in domestic condiments, and known to cause cancer cell death via redox mechanisms. Based on the structural features of these compounds we designed and synthesized several 2-cinnamamido-N-substituted-cinnamamide (bis-cinnamamide) compounds. One of the derivatives, (Z)-2-[(E)-cinnamamido]-3-phenyl-N-propylacrylamide 8 showed a moderate antiproliferative potency (HCT-116 cell line inhibition of 32.0 mu M), no inhibition of normal cell lines C-166, and proven cellular activities leading to apoptosis. SAR studies led to more than 10-fold increase in activity. Our most promising compound, [(Z)-3-(1H-indol-3-yl)-N-propyl-2-[(E)-3-(thien-2-yl)propenamido) propenamide] 45 killed colon cancer cells at IC50 = 0.89 mu M (Caco-2), 2.85 mu M (HCT-116) and 1.65 mu M (HT -29), while exhibiting much weaker potency on C-166 and BHK normal cell lines (IC50 = 71 mu M and 77.6 mu M, respectively). Cellular studies towards identifying the compounds mechanism of cytotoxic activities revealed that apoptotic induction occurs in part as a result of oxidative stress. Importantly, the compounds showed inhibition of cancer stem cells that are critical for maintaining the potential for self-renewal and stemness. The results presented here show discovery of covalently acting Michael addition compounds that potently kill cancer cells by a defined mechanism, with prominent selectivity profile over non-cancerous cell lines.
• Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore
  作者：Esteban P Urriolabeitia、Pablo Sánchez、Alexandra Pop、Cristian Silvestru、Eduardo Laga、Ana I Jiménez、Carlos Cativiela

  DOI：10.3762/bjoc.16.98

  日期：——

  face-to-face arrangement, which is optimal for their [2 + 2] photocycloaddition. Irradiation of dimers 3 in CH2Cl2 solution with blue light (465 nm) promoted the chemo- and stereoselective [2 + 2] photocycloaddition of the exocyclic C=C bonds and the formation of cyclobutane-containing ortho-palladated complexes 4. Treatment of 4 with CO in a MeOH/NCMe mixture promoted the methoxycarbonylation of the palladated

  据报道，由多官能恶唑酮立体合成合成木耳二氨基酯。4-（（Z）-亚芳基）-2-（E）-styryl-5（4 H）-恶唑酮2与Pd（OAc）2的反应导致邻位pal合并形成双核开卷复合物带有羧酸盐桥的3，其中Pd原子是与恶唑酮键合的C ^ N。在3中，恶唑酮的两个环外C = C键面对面排列，这对于它们的[2 + 2]光环加成是最佳的。在CH 2 Cl 2中辐照二聚体3蓝光（465 nm）的溶液促进了环外C = C键的化学和立体选择[2 + 2]光环加成反应，并形成了含环丁烷的邻钯配合物4。在MeOH / NCMe混合物中用CO处理4促进了钯化的碳的甲氧基羰基化，并释放了作为单一异构体的相应的邻官能化的1，3-二氨基苯甲基双氨基酯5。