(2E)-N-(2-methoxy-5-nitrophenyl)-3-phenylprop-2-enamide

• 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-(2-methoxy-5-nitrophenyl)-3-phenylprop-2-enamide
• 英文别名: cinnamic acid-(2-methoxy-5-nitro-anilide)；4-Nitro-2-cinnamoylamino-phenol-methylaether；Zimtsaeure-(2-methoxy-5-nitro-anilid)；4-Nitro-2-cinnamoylamino-anisol；(E)-N-(2-methoxy-5-nitrophenyl)-3-phenylprop-2-enamide
• 化学式: C₁₆H₁₄N₂O₄
• 分子量: 298.298
• InChiKey: GJWJVLBLBWRSOE-JXMROGBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-甲氧基-3-硝基苯甲酸 在 ammonium sulfide 、 硝酸 作用下， 生成 (2E)-N-(2-methoxy-5-nitrophenyl)-3-phenylprop-2-enamide
  参考文献：
  名称：

  Adrenocortical Dysfunction Following Etomidate Induction in Emergency Department Patients

  摘要：

  Abstract. Objective: To assess adrenocortical function following intravenous etomidate use in emergency department (ED) patients requiring intubation. Methods: This was a prospective, randomized, controlled trial of consecutive patients presenting to the ED requiring intubation. Patients were randomized to receive a single bolus induction dose of either 0.05‐0.1 mg/kg midazolam (control group) or 0.3 mg/kg etomidate (etomidate group) during a standardized rapid‐sequence intubation (RSI) with succinylcholine. The primary outcome variable was adrenocortical function at 4, 12, and 24 hours post‐induction as assessed by measured serum cortisol response to exogenous cosyntropin (cosyntropin stimulation test, CST). Fisher's exact test was used to compare CST results between groups. Results: Thirty‐one patients were enrolled: 8 control, 10 etomidate, and 13 excluded from analysis for either incomplete data or steroid use during the study period. The 4‐hour CST results were significantly different between study groups, with a normal response in 100% of control patients vs 30% of etomidate patients (p = 0.004). The 12‐ and 24‐hour CSTs did not differ significantly between groups: normal CST in 100% of control patients at 12 and 24 hours vs 100% and 90% among etomidate patients at 12 and 24 hours, respectively (p = 1.0 at 12 and 24 hours). Measured cortisol levels of patients with abnormal CSTs remained within normal laboratory reference ranges. Conclusion: Use of etomidate in ED patients requiring RSI results in adrenocortical dysfunction. However, cortisol levels remain within normal laboratory levels during this period of dysfunction. Adrenocortical dysfunction appears to resolve within 12 hours of a single bolus dose of 0.3 mg/kg etomidate.

  DOI：

  10.1111/j.1553-2712.2001.tb00537.x

文献信息

• Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives
  作者：Jan Hošek、Jiří Kos、Tomáš Strhársky、Lucie Černá、Pavel Štarha、Ján Vančo、Zdeněk Trávníček、Ferdinand Devínsky、Josef Jampílek

  DOI：10.3390/molecules24244531

  日期：——

  A series of sixteen ring-substituted N-arylcinnamanilides, previously described as highly antimicrobially effective against a wide spectrum of bacteria and fungi, together with two new derivatives from this group were prepared and characterized. Moreover, the molecular structure of (2E)-N-(2-bromo-5-fluorophenyl)-3-phenylprop-2-enamide as a model compound was determined using single-crystal X-ray analysis. All the compounds were tested for their anti-inflammatory potential, and most tested compounds significantly attenuated the lipopolysaccharide-induced NF-κB activation and were more potent than the parental cinnamic acid. (2E)-N-[2-Chloro-5-(trifluoromethyl)phenyl]-3-phenylprop-2-enamide, (2E)-N-(2,6-dibromophenyl)- 3-phenylprop-2-enamide, and (2E)-N-(2,5-dichlorophenyl)-3-phenylprop-2-enamide demonstrated the highest inhibition effect on transcription factor NF-κB at the concentration of 2 µM and showed a similar effectiveness as the reference drug prednisone. Several compounds also decreased the level of TNF-α. Nevertheless, subsequent tests showed that the investigated compounds affect neither IκBα level nor MAPKs activity, which suggests that the N-arylcinnamanilides may have a different mode of action to prednisone. The modification of the C(2,5)ʹ or C(2,6)ʹ positions of the anilide core by rather lipophilic and bulky moieties seems to be preferable for the anti-inflammatory potential of these compounds.

  一系列十六个环取代的N-芳基肉桂酰胺衍生物，先前已被描述为对广谱细菌和真菌高度抗菌有效，与该组的两个新衍生物一起被制备和表征。此外，使用单晶X射线分析确定了（2E）-N-（2-溴-5-氟苯基）-3-苯基丙烯酰胺作为模型化合物的分子结构。所有化合物都被测试其抗炎潜力，大多数测试化合物显著减弱了脂多糖诱导的NF-κB活化，并且比母体肉桂酸更有效。 （2E）-N- [2-氯-5-（三氟甲基）苯基] -3-苯基丙烯酰胺，（2E）-N-（2,6-二溴苯基）-3-苯基丙烯酰胺和（2E）-N-（2,5-二氯苯基）-3-苯基丙烯酰胺在2微米的浓度下表现出对转录因子NF-κB的最高抑制作用，并且显示出与参考药品泼尼松相似的效果。几种化合物还降低了TNF-α的水平。然而，随后的测试表明，所调查的化合物既不影响IκBα水平也不影响MAPKs活性，这表明N-芳基肉桂酰胺可能具有与泼尼松不同的作用模式。通过将苯酰胺核心的C（2,5）'或C（2,6）'位置修饰为较亲脂性和笨重的基团，似乎更有利于这些化合物的抗炎潜力。
• Insights into Antimalarial Activity of N-Phenyl-Substituted Cinnamanilides
  作者：Jiri Kos、Gilles Degotte、Dominika Pindjakova、Tomas Strharsky、Timotej Jankech、Tomas Gonec、Pierre Francotte、Michel Frederich、Josef Jampilek

  DOI：10.3390/molecules27227799

  日期：——

  Due to the urgent need of innovation in the antimalarial therapeutic arsenal, a series of thirty-seven ring-substituted N-arylcinnamanilides prepared by microwave-assisted synthesis were subjected to primary screening against the chloroquine-sensitive strain of P. falciparum 3D7/MRA-102. The lipophilicity of all compounds was experimentally determined as the logarithm of the capacity factor k, and these data were subsequently used in the discussion of structure-activity relationships. Among the screened compounds, fourteen derivatives exhibited IC50 from 0.58 to 31 µM, whereas (2E)-N-(4-bromo-2-chlorophenyl)-3-phenylprop-2-enamide (24) was the most effective agent (IC50 = 0.58 µM). In addition, (2E)-N-[2,6-dibromo-4-(trifluoromethyl)- phenyl]-3-phenylprop-2-enamide (36), (2E)-N-[4-nitro-3-(trifluoromethyl)phenyl]-3-phenylprop- 2-enamide (18), (2E)-N-(2-bromo-5-fluorophenyl)-3-phenylprop-2-enamide (23), and (2E)-3-phenyl-N-(3,4,5-trichlorophenyl)prop-2-enamide (33) demonstrated efficacy in the IC50 range from 2.0 to 4.3 µM, comparable to the clinically used standard chloroquine. The results of a cell viability screening performed using THP1-Blue™ NF-κB cells showed that none of these highly active compounds displayed any significant cytotoxic effect up to 20 μM, which makes them promising Plasmodium selective substances for further investigations.

  由于抗疟治疗药库急需创新，我们对微波辅助合成法制备的一系列 37 种环状取代的 N-芳基肉桂酰苯胺进行了初筛，以对抗对氯喹敏感的恶性疟原虫 3D7/MRA-102菌株。所有化合物的亲脂性都是通过实验测定的，即能力因子 k 的对数，这些数据随后被用于结构-活性关系的讨论。在筛选出的化合物中，有 14 种衍生物的 IC50 值在 0.58 到 31 µM 之间，而 (2E)-N-(4-bromo-2-chlorophenyl)-3-phenylprop-2-enamide (24) 是最有效的药剂（IC50 = 0.58 µM）。(2E)-N-(2-溴-5-氟苯基)-3-苯基丙-2-烯酰胺(23)和(2E)-3-苯基-N-(3,4,5-三氯苯基)丙-2-烯酰胺(33)的药效 IC50 范围为 2.0 至 4.3 µM，与临床使用的标准氯喹相当。使用 THP1-Blue™ NF-κB 细胞进行的细胞活力筛选结果表明，这些高活性化合物在 20 μM 以下均未显示出任何明显的细胞毒性作用，这使它们成为有望进一步研究的疟原虫选择性物质。
• Adrenocortical Dysfunction Following Etomidate Induction in Emergency Department Patients
  作者：Christina L. Schenarts、John H. Burton、Richard R. Riker

  DOI：10.1111/j.1553-2712.2001.tb00537.x

  日期：2001.1

  Abstract. Objective: To assess adrenocortical function following intravenous etomidate use in emergency department (ED) patients requiring intubation. Methods: This was a prospective, randomized, controlled trial of consecutive patients presenting to the ED requiring intubation. Patients were randomized to receive a single bolus induction dose of either 0.05‐0.1 mg/kg midazolam (control group) or 0.3 mg/kg etomidate (etomidate group) during a standardized rapid‐sequence intubation (RSI) with succinylcholine. The primary outcome variable was adrenocortical function at 4, 12, and 24 hours post‐induction as assessed by measured serum cortisol response to exogenous cosyntropin (cosyntropin stimulation test, CST). Fisher's exact test was used to compare CST results between groups. Results: Thirty‐one patients were enrolled: 8 control, 10 etomidate, and 13 excluded from analysis for either incomplete data or steroid use during the study period. The 4‐hour CST results were significantly different between study groups, with a normal response in 100% of control patients vs 30% of etomidate patients (p = 0.004). The 12‐ and 24‐hour CSTs did not differ significantly between groups: normal CST in 100% of control patients at 12 and 24 hours vs 100% and 90% among etomidate patients at 12 and 24 hours, respectively (p = 1.0 at 12 and 24 hours). Measured cortisol levels of patients with abnormal CSTs remained within normal laboratory reference ranges. Conclusion: Use of etomidate in ED patients requiring RSI results in adrenocortical dysfunction. However, cortisol levels remain within normal laboratory levels during this period of dysfunction. Adrenocortical dysfunction appears to resolve within 12 hours of a single bolus dose of 0.3 mg/kg etomidate.