(E)-N-(1-羟基丙-2-基)-3-苯基丙-2-烯酰胺 | 30687-18-4

• 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: (E)-N-(1-羟基丙-2-基)-3-苯基丙-2-烯酰胺
• 英文名称: (R,S)-(E)-N-(1-hydroxypropan-2-yl)-3-phenylprop-2-enamide
• 英文别名: N-(2-Hydroxy-1-methylethyl)cinnamamide；(E)-N-(1-hydroxypropan-2-yl)-3-phenylprop-2-enamide
• CAS: 30687-18-4
• 化学式: C₁₂H₁₅NO₂
• 分子量: 205.257
• InChiKey: FCIUATHUXGLRRQ-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  (E)-N-(1-羟基丙-2-基)-3-苯基丙-2-烯酰胺 、 乙酸酐 以62%的产率得到(R,S)-2-{[(2E)-3-phenylprop-2-enoyl]amino}propyl acetate
  参考文献：
  名称：

  Anticonvulsant activity, crystal structures, and preliminary safety evaluation of N-trans-cinnamoyl derivatives of selected (un)modified aminoalkanols

  摘要：

  Adequate control of seizures remains an unmet need in epilepsy. In order to identify new anticonvulsant agents, a series of N-trans-cinnamoyl derivatives of selected aminoalkanols was synthetized. The compounds were obtained in the reaction of N-acylation carried out in a two-phase system. The substances were tested in animal models of seizures induced either electrically (maximal electroshock - MES; 6-Hz test) or chemically, by subcutaneous injection of pentetrazol (scPTZ). Neurotoxicity was determined by the rotarod test. Lipophilicity of the active compounds, expressed as R-M0, was determined by reversed-phase thin layer chromatography and it ranged from 1.390 to 2.219. From among the tested series of compounds, R,S-(E)-N-(1-hydroxypropan-2-yl)-3-phenylprop-2-enamide (1) and R,S-(E)-N-(2-hydroxypropyl)-3-phenylprop-2-enamide (3) exhibited the best anticonvulsant activity. Compound 1, when administered to mice by intraperitoneal (i.p.) injection, showed the ED50 values of 86.6, 60.9, and 109.6 mg/kg in the MES, 6-Hz, and scPTZ tests, respectively. For compound 3, the ED50 values were found to be 47.1 mg/kg in MES and 77.1 mg/kg in scPTZ (mice, i.p.). The distances measured in crystals of compound 1 were: 7.99 angstrom - from the phenyl ring to the hydroxyl group in the amide moiety, 5.729 angstrom - from the phenyl ring to the amide group, and 3.112 angstrom - from the amide group to the hydroxyl group in the amide moiety. The reported compounds did not exhibit mutagenic potential when assayed in the Ames test. Compounds 1 and 3 did not affect viability and morphology of human hepatocellular carcinoma cells (HepG2). (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.051
• 作为产物：
  描述：

  DL-氨基丙醇 、 3-苯基-2-丙烯酰氯 在 potassium carbonate 作用下， 以 甲苯 为溶剂， 生成 (E)-N-(1-羟基丙-2-基)-3-苯基丙-2-烯酰胺
  参考文献：
  名称：

  Anti-Helicobacter pylori activities of selected N-substituted cinnamamide derivatives evaluated on reference and clinical bacterial strains

  摘要：

  在本项研究中，使用琼脂平板扩散法对三十五种N-取代肉桂酸酰胺（肉桂酰胺）衍生物进行了抗幽门螺杆菌活性评估。通过对参考幽门螺杆菌菌株（ATCC 43504）的定性筛选，鉴定出三种最具活性的化合物，分别为8号（R,S-(2E)-3-(4-氯苯基)-N-(2-羟丙基)丙-2-烯酰胺，最小抑制浓度MIC=7.5μg/mL）、23号（(2E)-3-(4-氯苯基)-N-(2-羟环己基)丙-2-烯酰胺，MIC=10μg/mL）和28号（(2E)-3-(4-氯苯基)-N-(4-氧环己基)丙-2-烯酰胺，MIC=10μg/mL）。随后，这些化合物在十二种特征明确的临床菌株上进行了进一步测试，得到的MIC值范围从10到1000μg/mL不等。通过MTT活力度测试评估细胞毒性和Ames试验评估诱变性，对这些化合物进行了初步安全性评估，结果显示它们总体上是安全的，尽管在某些测试浓度下，8号和28号化合物表现出诱变活性。本研究结果表明，肉桂酰胺衍生物具有抗幽门螺杆菌的潜力。

  DOI：

  10.1038/s41429-018-0027-1

文献信息

• Anti-Helicobacter pylori activities of selected N-substituted cinnamamide derivatives evaluated on reference and clinical bacterial strains
  作者：Karolina Klesiewicz、Elżbieta Karczewska、Paweł Nowak、Iwona Skiba-Kurek、Edward Sito、Katarzyna Pańczyk、Paulina Koczurkiewicz、Dorota Żelaszczyk、Elżbieta Pękala、Anna M. Waszkielewicz、Alicja Budak、Henryk Marona、Agnieszka Gunia-Krzyżak

  DOI：10.1038/s41429-018-0027-1

  日期：2018.5

  In this study, thirty-five N-substituted derivatives of cinnamic acid amide (cinnamamide) were evaluated for anti-Helicobacter pylori activity using an agar disc-diffusion method. Qualitative screening was performed on a reference H. pylori strain (ATCC 43504), resulting in the identification of the three most active compounds, 8 (R,S-(2E)-3-(4-chlorophenyl)-N-(2-hydroxypropyl)prop-2-enamide, minimal inhibitory concentration, MIC = 7.5 µg/mL), 23 ((2E)-3-(4-chlorophenyl)-N-(2-hydroxycyclohexyl)prop-2-enamide, MIC = 10 µg/mL), and 28 ((2E)-3-(4-chlorophenyl)-N-(4-oxocyclohexyl)prop-2-enamide, MIC = 10 µg/mL). These compounds were further tested on twelve well-characterized clinical strains, yielding MIC values that ranged from 10 to 1000 µg/mL. Preliminary safety assessments of the compounds were made using the MTT viability test for cytotoxicity and Ames test for mutagenicity, which showed them to be generally safe, although compounds 8 and 28 showed mutagenic activity at some of the tested concentrations. The results of this study showed the anti-H. pylori potential of cinnamamide derivatives.

  在本项研究中，使用琼脂平板扩散法对三十五种N-取代肉桂酸酰胺（肉桂酰胺）衍生物进行了抗幽门螺杆菌活性评估。通过对参考幽门螺杆菌菌株（ATCC 43504）的定性筛选，鉴定出三种最具活性的化合物，分别为8号（R,S-(2E)-3-(4-氯苯基)-N-(2-羟丙基)丙-2-烯酰胺，最小抑制浓度MIC=7.5μg/mL）、23号（(2E)-3-(4-氯苯基)-N-(2-羟环己基)丙-2-烯酰胺，MIC=10μg/mL）和28号（(2E)-3-(4-氯苯基)-N-(4-氧环己基)丙-2-烯酰胺，MIC=10μg/mL）。随后，这些化合物在十二种特征明确的临床菌株上进行了进一步测试，得到的MIC值范围从10到1000μg/mL不等。通过MTT活力度测试评估细胞毒性和Ames试验评估诱变性，对这些化合物进行了初步安全性评估，结果显示它们总体上是安全的，尽管在某些测试浓度下，8号和28号化合物表现出诱变活性。本研究结果表明，肉桂酰胺衍生物具有抗幽门螺杆菌的潜力。
• US4512994A
  申请人：——

  公开号：US4512994A

  公开（公告）日：1985-04-23
• Cinnamic acid derivatives as chemosensitising agents against DOX-treated lung cancer cells – Involvement of carbonyl reductase 1
  作者：Paulina Koczurkiewicz-Adamczyk、Kamil Piska、Agnieszka Gunia-Krzyżak、Adam Bucki、Marek Jamrozik、Ewelina Lorenc、Damian Ryszawy、Katarzyna Wójcik-Pszczoła、Marta Michalik、Henryk Marona、Marcin Kołaczkowski、Elżbieta Pękala

  DOI：10.1016/j.ejps.2020.105511

  日期：2020.11

  was simulated by molecular modelling studies. The kinetics of DOX reduction in the presence of active CA derivatives were measured in cytosols. The chemosensitising activity of CA derivatives including proapoptotic, anti-invasiveness activity were investigated in A549 lung cancer cell line. In our research 7 from 16 tested CA derivatives binded to the active site of CBR1 enzyme and improved DOX stability

  阿霉素（DOX）治疗受到癌细胞耐药性和心脏毒性的限制。还原酶（主要由CBR1；羰基还原酶1）将DOX生物转化为阿霉素（DOXol）是负责DOX不良反应发展的关键过程。因此，抑制CBR1可以提高DOX的治疗效果。在本研究中，我们使用了一组新的合成肉桂酸（CA）衍生物来提高DOX体外治疗癌细胞的有效性和安全性。 通过分子模型研究模拟了CBR1抑制的可能机制。在细胞溶胶中测量了在活性CA衍生物存在下DOX还原的动力学。研究了CA衍生物在A549肺癌细胞系中的化学增敏活性，包括促凋亡，抗侵袭活性。 在我们的研究中，从16种经过测试的CA衍生物中有7种与CBR1酶的活性位点结合，并通过抑制DOXol的形成提高了DOX的稳定性。A549细胞与活性CA衍生物和DOX共同处理通过激活caspase级联反应诱导细胞凋亡。同时，我们观察到CA衍生+ DOX处理的细胞中侵袭性下降（细胞迁移和迁移分析）和F-肌动
• Anticonvulsant activity, crystal structures, and preliminary safety evaluation of N-trans-cinnamoyl derivatives of selected (un)modified aminoalkanols
  作者：Agnieszka Gunia-Krzyżak、Ewa Żesławska、Karolina Słoczyńska、Paulina Koczurkiewicz、Wojciech Nitek、Dorota Żelaszczyk、Natalia Szkaradek、Anna M. Waszkielewicz、Elżbieta Pękala、Henryk Marona

  DOI：10.1016/j.ejmech.2015.10.051

  日期：2016.1

  Adequate control of seizures remains an unmet need in epilepsy. In order to identify new anticonvulsant agents, a series of N-trans-cinnamoyl derivatives of selected aminoalkanols was synthetized. The compounds were obtained in the reaction of N-acylation carried out in a two-phase system. The substances were tested in animal models of seizures induced either electrically (maximal electroshock - MES; 6-Hz test) or chemically, by subcutaneous injection of pentetrazol (scPTZ). Neurotoxicity was determined by the rotarod test. Lipophilicity of the active compounds, expressed as R-M0, was determined by reversed-phase thin layer chromatography and it ranged from 1.390 to 2.219. From among the tested series of compounds, R,S-(E)-N-(1-hydroxypropan-2-yl)-3-phenylprop-2-enamide (1) and R,S-(E)-N-(2-hydroxypropyl)-3-phenylprop-2-enamide (3) exhibited the best anticonvulsant activity. Compound 1, when administered to mice by intraperitoneal (i.p.) injection, showed the ED50 values of 86.6, 60.9, and 109.6 mg/kg in the MES, 6-Hz, and scPTZ tests, respectively. For compound 3, the ED50 values were found to be 47.1 mg/kg in MES and 77.1 mg/kg in scPTZ (mice, i.p.). The distances measured in crystals of compound 1 were: 7.99 angstrom - from the phenyl ring to the hydroxyl group in the amide moiety, 5.729 angstrom - from the phenyl ring to the amide group, and 3.112 angstrom - from the amide group to the hydroxyl group in the amide moiety. The reported compounds did not exhibit mutagenic potential when assayed in the Ames test. Compounds 1 and 3 did not affect viability and morphology of human hepatocellular carcinoma cells (HepG2). (C) 2015 Elsevier Masson SAS. All rights reserved.