4-[1-氧代-3-(3,4,5-三甲氧基苯基)-2-丙烯基]吗啉 | 1703-34-0

• 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
• 中文名称: 4-[1-氧代-3-(3,4,5-三甲氧基苯基)-2-丙烯基]吗啉
• 英文名称: (E)-1-morpholino-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• 英文别名: 4-(3,4,5-Trimethoxycinnamoyl)morpholine；(E)-1-morpholin-4-yl-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 1703-34-0
• 化学式: C₁₆H₂₁NO₅
• 分子量: 307.346
• InChiKey: FACQYSYWUYJQCQ-SNAWJCMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  4-[1-氧代-3-(3,4,5-三甲氧基苯基)-2-丙烯基]吗啉 生成 4-(3,4,5-Trimethoxybenzenepropionyl)morpholine
  参考文献：
  名称：

  FARINA C.; PELLEGATA R.; PINZA M.; PIFFERI G., ARCH. PHARM., 1981, 314, NO 2, 108-117

  摘要：

  DOI：
• 作为产物：
  描述：

  3,4,5-三甲基肉桂酸甲酯 在 三甲基铝 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 28.5h， 生成 4-[1-氧代-3-(3,4,5-三甲氧基苯基)-2-丙烯基]吗啉
  参考文献：
  名称：

  反式-3,4,5-三甲氧基肉桂酰胺的简单合成及其生物学活性评估

  摘要：

  一个简单的合成和生物评价反式-3,4,5-三甲氧基肉桂酰胺10a-e和11作为新型抗麻醉药。合成关键策略涉及缩合反应和偶联反应，以生成反式-3,4,5-三甲氧基肉桂酰胺10a–e和11。对它们的自由基清除，培养的神经元对神经毒性的抑制作用以及小鼠的抗麻醉活性进行了评估。研究发现，化合物10a，10d和10e对谷氨酸诱导的神经毒性具有明显的抑制作用，而10a–e和11则具有抑制作用。 在小鼠中显示出高的抗麻醉活性。

  DOI：

  10.1007/s00044-012-0415-1

文献信息

• Design, synthesis and antibacterial activity of cinnamaldehyde derivatives as inhibitors of the bacterial cell division protein FtsZ
  作者：Xin Li、Juzheng Sheng、Guihua Huang、Ruixin Ma、Fengxin Yin、Di Song、Can Zhao、Shutao Ma

  DOI：10.1016/j.ejmech.2015.04.048

  日期：2015.6

  exerted superior or comparable activity to all the reference drugs. In the cell division inhibitory activity, all the compounds showed the same trend as their in vitro antibacterial activity, exhibiting better activity against S. aureus ATCC25923 than the other strains. Additionally, compounds 3, 6, 7 and 8 displayed potent cell division inhibitory activity with an MIC value of below 1 μg/mL, over 256-fold

  为了发现潜在的抗细菌耐药性增强剂，设计，合成和评估了新型肉桂醛衍生物作为FtsZ抑制剂，使用肉汤微稀释法评估了其对九种重要病原体的抗菌活性，以及​​它们对四种代表性菌株的细胞分裂抑制活性。在体外抗菌活性中，新合成的化合物一般对金黄色葡萄球菌ATCC25923显示出比其他化合物更好的功效。特别是化合物3，8和10发挥了优于所有参比药物的活性。在细胞分裂抑制活性中，所有化合物均显示出与其体外抗菌活性相同的趋势，与其他菌株相比，其对金黄色葡萄球菌ATCC25923的活性更好。此外，化合物3，6，7和8中显示强效的细胞分裂的抑制活性具有低于1微克/毫升，超过256倍更好所有参考药物的MIC值。
• Design, synthesis and biological evaluation of (E)-3-(3,4,5-trimethoxyphenyl) acrylic acid (TMCA) amide derivatives as anticonvulsant and sedative agents
  作者：Zefeng Zhao、Yajun Bai、Xufei Chen、Shaoping Wu、Xirui He、Yujun Bai、Ying Sun、Xiaohui Zheng

  DOI：10.1007/s00044-018-2228-3

  日期：2018.12

  article, a novel series of (E)-3-(3,4,5-trimethoxyphenyl)acrylic acid (TMCA) amide derivatives 1-18 were designed and synthesized by a facile and one-pot step, which were achieved with good yields using 1-hydroxybenzotriazole (HOBT) and 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) as activation system. All the synthesized derivatives were biologically evaluated for their anticonvulsant

  本文设计了一系列新颖的（E）-3-（3,4,5-三甲氧基苯基）丙烯酸（TMCA）酰胺衍生物1-18，并通过简单的一锅法步骤合成了使用1-羟基苯并三唑（HOBT）和1-（3-二甲基氨基丙基）-3-乙基碳二亚胺盐酸盐（EDCI）作为活化体系可得到良好的收率。分别使用最大电击（MES）模型，sc-戊烯四唑（PTZ）模型，戊巴比妥钠诱发的睡眠模型和运动功能测试，对所有合成衍生物的抗惊厥，镇静活性和神经毒性进行了生物学评估。其中，化合物4、9和16在初步评估中表现出良好的抗惊厥活性。此外，化合物4是随后测试中最有效的抗惊厥药和镇静剂，而化合物4的低毒性阈值则保持警惕。在随后的测试中，化合物9和16还具有明显的抗惊厥活性，且毒性较弱。分子建模实验还预测了获得的活性分子与GABA转移蛋白的良好结合相互作用。因此，可以得出结论，合成的衍生物4、9和16将代表有用的先导化合物，用于进一步研究抗惊厥药和镇静剂。
• Synthesis and Evaluation of a Series of 3,4,5-Trimethoxycinnamic Acid Derivatives as Potential Antinarcotic Agents
  作者：Jae-Chul Jung、Sohyeon Moon、Dongguk Min、Woo Kyu Park、Mankil Jung、Seikwan Oh

  DOI：10.1111/cbdd.12087

  日期：2013.3

  A series of 3,4,5‐trimethoxycinnamic acid derivatives was prepared and evaluated for antinarcotic effects on morphine dependence in mice and binding affinities on serotonergic receptors. The key synthetic strategies involve generation of ketones 6–7, esters 9–12 through condensation reaction, and amides 13–19 via coupling reaction using 1‐hydroxybenzotriazole/ethyl(dimethylaminopropryl)carbodiimide system in high yield. We found that the naloxone‐induced morphine withdrawal syndrome was significantly suppressed by new synthetic 3,4,5‐trimethoxycinnamic acid derivatives (20 mg/kg/day). Most of 3,4,5‐trimethoxycinnamic acid derivatives were found to have high affinity to 5‐HT1A receptor. The naloxone‐induced morphine withdrawal syndrome was attenuated by (+)8‐OH‐DPAT (0.1 mg/kg/day, i.p.), a 5‐HT1A receptor agonist. In cortical neuronal cells, (+)8‐OH‐DPAT (1 μm) produced an elevation of the pERK 1/2 expression, and the elevated pERK levels were inhibited by WAY 100635, a 5‐HT1A receptor‐specific antagonist. Interestingly, the pERK levels were increased by the 3,4,5‐trimethoxycinnamic acid derivatives and the derivatives‐mediated changes in pERK levels were blocked by the WAY 100635. These results suggested that new synthetic 3,4,5‐trimethoxycinnamic acid derivatives have a potential antinarcotic effect through acting as a 5‐HT1A receptor agonist in mice.
• Synthesis of piplartine analogs and preliminary findings on structure–antimicrobial activity relationship
  作者：Antonio Maciel Fregnan、Guilherme Andrade Brancaglion、Alexandre Francisco Cerqueira Galvão、Cinara Oliveira D’Sousa Costa、Diogo Rodrigo Magalhães Moreira、Milena Botelho Pereira Soares、Daniel Pereira Bezerra、Naiara Chaves Silva、Stella Maria de Souza Morais、Josidel Conceição Oliver、Amanda Latercia Tranches Dias、Luiz Felipe Leomil Coelho、Diogo Teixeira Carvalho、Danielle Ferreira Dias、Thiago Belarmino de Souza

  DOI：10.1007/s00044-016-1774-9

  日期：2017.3

  In this work it is described the synthesis, characterization and antimicrobial and toxicity evaluation of a series of analogs of piplartine, a piperamide found in Piper sp. The compounds structures were confirmed by infrared spectroscopy, H-1, C-13 nuclear magnetic resonance, high resolution mass spectroscopy and were evaluated against strains of Candida spp., Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Derivative 24 was almost four-fold more potent (IC50: 48.83 mu M) and five-fold less toxic (SI > 3) than piplartine (IC50: 189.2 mu M; SI: 0.21) against Candida krusei, as well as two-fold more potent than fluconazole (IC50: 104.48 mu M). This compound was also active against Candida tropicalis at 97.67 mu M. Benzoyl derivative 17 was three-fold more potent (IC50: 85.2 mu M) and more than five-fold less toxic (CC50: 231.71 mu M) than piplartine (IC50: 315.33 mu M and CC50: 41.14 mu M) against Staphylococcus aureus. Given these findings, we have found analogs of piplartine which can be assumed as prototypes for the optimization and the development of new antimicrobial (compounds 24 and 17) agents.