4-benzyl-1-[(1-methylpyrrol-2-yl)acetyl]semicarbazide | 1217115-24-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-benzyl-1-[(1-methylpyrrol-2-yl)acetyl]semicarbazide
• 英文别名: 1-Benzyl-3-[[2-(1-methylpyrrol-2-yl)acetyl]amino]urea
• CAS: 1217115-24-6
• 化学式: C₁₅H₁₈N₄O₂
• 分子量: 286.334
• InChiKey: DNAHWAPPKQYZCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75.2
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-benzyl-1-[(1-methylpyrrol-2-yl)acetyl]semicarbazide 在 sodium hydroxide 作用下， 生成 4-benzyl-3-[(1-methylpyrrol-2-yl)methyl]-4,5-dihydro-1H-1,2,4-triazol-5-one
  参考文献：
  名称：

  Structural and Molecular Docking Studies of 4-Benzyl-3-[(1-methylpyrrol- 2-yl)methyl]-4,5-dihydro-1H-1,2,4-triazol-5-one with Anticancer Activity

  摘要：

  1,2,4-三唑类药物是一类重要的药物，具有多种活性，例如止痛、抗菌、杀菌、消炎、抗病毒和抗癌。作为我们对1,2,4-三唑类药物长期研究的一部分，我们合成了4-苄基-3-[(1-甲基吡咯-2-基)甲基]-4,5-二氢-1H-1,2,4-三唑-5-酮，其抗癌活性是它的主要特征。在此，我们对其电子和分子结构进行了详尽的研究，旨在通过分子对接到EGFR激酶域ATP结合位点来合理化所观察到的药理活性。结构研究包括X射线分析、实验和计算光谱分析（1H和13C NMR、IR）以及构象分析和正面分子轨道（FMO）分析。分子对接的结果表明，4-苄基-3-[(1-甲基吡咯-2-基)甲基]-4,5-二氢-1H-1,2,4-三唑-5-酮与EGFR激酶域ATP结合位点的相互作用可能是这种1,2,4-三唑衍生物所观察到的抗癌活性的原因。此外，我们发现，相应配体-蛋白复合物的形成受配体的酮-烯醇互变异构的影响，即酮形式的能量优势。

  DOI：

  10.2174/1573406411309030002
• 作为产物：
  描述：

  2-(1-甲基-1H-吡咯-2-基)乙酰肼 、 异氰酸苄酯 以 N,N-二甲基乙酰胺 为溶剂， 反应 24.0h， 以76%的产率得到4-benzyl-1-[(1-methylpyrrol-2-yl)acetyl]semicarbazide
  参考文献：
  名称：

  Determination of the Lipophilicity of Some New Derivatives of Semicarbazide and 1,2,4-Triazol-5-one with Potential Antibacterial Activity

  摘要：

  新的1,2,4-三唑-5-酮和半卡巴肼衍生物的色谱行为已被确定。使用RP-TLC方法确认了它们的亲脂性。使用理论程序计算了它们的分配系数。确定了理论和实验亲脂性之间的相关性。对所有获得的化合物进行了抗微生物活性测试。

  DOI：

  10.1515/znb-2009-0514

文献信息

• Determination of the Lipophilicity of Some New Derivatives of Semicarbazide and 1,2,4-Triazol-5-one with Potential Antibacterial Activity
  作者：Monika Pitucha、Beata Polak、Ryszard Świebodac、Urszula Kosikowska、Anna Malm

  DOI：10.1515/znb-2009-0514

  日期：2009.5.1

  The chromatographic behavior of new derivatives of 1,2,4-triazol-5-one and semicarbazide was determined. The lipophilicity was confirmed by the use of a RP-TLC method. The partition coefficients were calculated by use of theoretical procedures. The correlation between theoretical and experimental lipophilicity was determined. All obtained compounds were tested for their antimicrobial activity.

  新的1,2,4-三唑-5-酮和半卡巴肼衍生物的色谱行为已被确定。使用RP-TLC方法确认了它们的亲脂性。使用理论程序计算了它们的分配系数。确定了理论和实验亲脂性之间的相关性。对所有获得的化合物进行了抗微生物活性测试。
• Experimental and theoretical investigations on the keto–enol tautomerism of 4-substituted 3-[1-methylpyrrol-2-yl)methyl]-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives
  作者：Monika Pitucha、Zbigniew Karczmarzyk、Waldemar Wysocki、Agnieszka A. Kaczor、Dariusz Matosiuk

  DOI：10.1016/j.molstruc.2011.03.041

  日期：2011.5

  possessing the carbonyl group. In the present study we use X-ray analysis, IR spectroscopy as well as quantum chemical calculation to address the keto–enol tautomerism of 4-substituted 3-[1-methylpyrrol-2-yl)methyl]-4,5-dihydro-1 H -1,2,4-triazol-5-one derivatives with antimicrobial activity. In the gas phase and in the crystalline state all the investigated molecules exist in the keto form while in the

  摘要 酮-烯醇互变异构是决定具有羰基的化合物药理活性的关键现象。在本研究中，我们使用 X 射线分析、红外光谱以及量子化学计算来解决 4-取代 3-[1-甲基吡咯-2-基)甲基]-4,5-二氢- 1 H -1,2,4-triazol-5-one 衍生物，具有抗菌活性。在气相和结晶状态下，所有研究的分子都以酮形式存在，而在氯仿溶液中，观察到少量与酮形式平衡的烯醇形式。计算结果与在 KBr 中从 X 射线分析和红外光谱获得的实验数据非常一致，但不能证实互变异构平衡在氯仿溶液中转变为烯醇形式。
• Synthesis and RP HPLC studies of biologically active semicarbazides and their cyclic analogues 1,2,4-triazol-3-ones
  作者：Monika Pitucha、Joanna Matysiak、Bogdan Senczyna

  DOI：10.1007/s00706-011-0715-z

  日期：2012.4

  The retention behaviour of semicarbazides and their cyclic analogues 1,2,4-triazol-3-ones, has been investigated by RP-8, RP-18 and IAM HPLC. The structures of new derivatives were proved by elemental analyses, IR, H-1 NMR and C-13 NMR spectroscopy. The compounds showed regular retention behaviour in three chromatographic systems; their log k values decreased linearly with the increasing concentration of an organic modifier in the mobile phase. The ratio of the intercept (log k (w)) to the slope of compounds is constant and the same for both groups of compounds on C18 and IAM stationary phases. Differences between log k (w) values from the octadecyl stationary phase of corresponding cyclic and linear derivatives are constant, and they are related to the mechanism of synthesis of 1,2,4-triazol-3-ones from linear substrate semicarbazides, which was confirmed by modelling studies. Good correlations between log k (w) parameters obtained by RP-8 or RP-18 and determined by the computational approach log P were found.
• Structural and Molecular Docking Studies of 4-Benzyl-3-[(1-methylpyrrol- 2-yl)methyl]-4,5-dihydro-1H-1,2,4-triazol-5-one with Anticancer Activity
  作者：Agnieszka A. Kaczor、Monika Pitucha、Zbigniew Karczmarzyk、Waldemar Wysocki、Jolanta Rzymowska、Dariusz Matosiuk

  DOI：10.2174/1573406411309030002

  日期：2013.2.1

  The 1,2,4-triazoles are an important group of medicinal substances which exhibit a wide range of activity, such as analgesic, antibacterial, fungicidal, antinflammatory, antiviral and anticancer. As a part of our long-term study on 1,2,4- triazoles we synthesize 4-benzyl-3-[(1-methylpyrrol-2-yl)methyl]-4,5-dihydro-1H-1,2,4-triazol-5-one which is characterized with anticancer activity. Here, we present an exhaustive studies of its electronic and molecular structure, aimed to rationalize the observed pharmacological activity, supported by the molecular docking to the EGFR kinase domain ATP binding site. The structural studies include X-ray analysis, experimental and computed spectral analysis (1H and 13C NMR, IR) as well as conformational analysis and the frontal molecular orbitals (FMO) analysis. The results of molecular docking indicate that interaction of 4-benzyl-3-[(1-methylpyrrol-2-yl)methyl]-4,5-dihydro-1H-1,2,4-triazol-5-one with the EGFR kinase domain ATP binding site may be responsible for the observed anticancer activity of this 1,2,4-triazole derivative. Moreover, we find that formation of the respective ligand-protein complex is conditioned by the keto-enol tautomerism of the ligand, i.e. the energetic prevalence of the keto form.

  1,2,4-三唑类药物是一类重要的药物，具有多种活性，例如止痛、抗菌、杀菌、消炎、抗病毒和抗癌。作为我们对1,2,4-三唑类药物长期研究的一部分，我们合成了4-苄基-3-[(1-甲基吡咯-2-基)甲基]-4,5-二氢-1H-1,2,4-三唑-5-酮，其抗癌活性是它的主要特征。在此，我们对其电子和分子结构进行了详尽的研究，旨在通过分子对接到EGFR激酶域ATP结合位点来合理化所观察到的药理活性。结构研究包括X射线分析、实验和计算光谱分析（1H和13C NMR、IR）以及构象分析和正面分子轨道（FMO）分析。分子对接的结果表明，4-苄基-3-[(1-甲基吡咯-2-基)甲基]-4,5-二氢-1H-1,2,4-三唑-5-酮与EGFR激酶域ATP结合位点的相互作用可能是这种1,2,4-三唑衍生物所观察到的抗癌活性的原因。此外，我们发现，相应配体-蛋白复合物的形成受配体的酮-烯醇互变异构的影响，即酮形式的能量优势。