(4S,8aS)-4-phenyl-perhydropyrrolo[1,2-a]pyrazine-1,3-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (4S,8aS)-4-phenyl-perhydropyrrolo[1,2-a]pyrazine-1,3-dione
• 英文别名: (4S,8aS)-4-phenylperhydropyrrole[1,2-a]pyrazine-1,3-dione；(4S,8aS)-4-phenylperhydropyrrolo[1,2-a]pyrazine-1,3-dione；(4S,8aS)-4-phenyl-6,7,8,8a-tetrahydro-4H-pyrrolo[1,2-a]pyrazine-1,3-dione
• 化学式: C₁₃H₁₄N₂O₂
• 分子量: 230.266
• InChiKey: HBBMDAQPPJMYRZ-QWRGUYRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4S,8aS)-4-phenyl-perhydropyrrolo[1,2-a]pyrazine-1,3-dione 、 乙基溴苯 在 四丁基溴化铵 、 potassium carbonate 、 盐酸 作用下， 以 丙酮 、 乙醚 为溶剂， 反应 1.0h， 以63%的产率得到(4S,8aS)-2-(2-phenylethyl)-4-phenyl-perhydropyrrole[1,2-a]pyrazine-1,3-dione hydrochloride
  参考文献：
  名称：

  新型2,6-二酮哌嗪衍生物的合成及其抗惊厥活性。第1部分：全氢吡咯[1,2- a ]吡嗪

  摘要：

  合成了许多新颖的吡咯[1,2- a ]吡嗪衍生物，并在癫痫的体内动物模型中进行了评估。其中，几种化合物在最大电击惊厥（MES），皮下甲硝唑惊厥（scMET），6 Hz和毛果芸香碱引起的状态预防（PISP）测试中显示出有希望的癫痫保护作用，其ED 50值可与参考抗惊厥药（AEDs）相提并论。 ）。观察到吡咯[1,2- a ]吡嗪核心的立体化学和构象偏好对体内药理活性的关键影响。合成药物的抗惊厥作用机制很可能不是通过抑制电压依赖性钠（Na+）电流。

  DOI：

  10.1016/j.ejmech.2011.07.027
• 作为产物：
  描述：

  L-扁桃酸甲酯 在 sodium ethanolate 、 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 12.67h， 生成 (4S,8aS)-4-phenyl-perhydropyrrolo[1,2-a]pyrazine-1,3-dione
  参考文献：
  名称：

  The synthesis of new diastereomers of (4S,8aS)- and (4R,8aS)-4-phenyl-perhydropyrrole[1,2-a]pyrazine-1,3-dione

  摘要：

  The synthesis of new (4S,8aS)- and (4R,8aS)-4-phenyl-perhydropyrrole[1,2-a]pyrazine-1,3-diones in the cyclocondensation reaction of the respective derivatives of L-prolineamide is described. The effect of the amount of NaOEt, temperature, and reaction time on the proportions of diastereomers formed in the cyclocondensation reaction was examined. The structures of the diastercomers were confirmed by GC/MS, FIRMS, HPLC; XRD, and H-1 and C-13 NMR investigations. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2007.08.025

文献信息

• Synthesis of New Perhydropyrrolo[1,2-a]pyrazine Derivatives and Their Evaluation in Animal Models of Epilepsy
  作者：Maciej Dawidowski、Wojciech Lewandowski、Jadwiga Turło

  DOI：10.3390/molecules191015955

  日期：——

  A series of novel stereochemically pure derivatives of the investigative broad-spectrum anticonvulsant ADD408003 was designed and synthesized. Five-center four-component (U-5C-4CR) and four-center three-component (U-4C-3CR) variants of Ugi reaction were used in the key step of the synthetic pathways. The compounds obtained were evaluated for the anticonvulsant activitiy in the maximal electroshock seizure (MES), subcutaneous Metrazole (scMET) and minimal clonic seizure (6 Hz) animal models of epilepsy. The efficacies of most derivatives in the 6 Hz model of pharmacoresistant partial seizures were markedly higher than in the ‘classical’ MES and scMET models. The most active compounds, (4R,8aR)-3a, and (4S,8aS)-6 displayed median effective doses (ED50) of 47.90 and 126.19 mg/kg, respectively, for the 6 Hz test.

  设计并合成了新型广谱抗惊厥药物ADD408003的一系列立体化学纯衍生物。在合成路径的关键步骤中，使用了五中心四组分（U-5C-4CR）和四中心三组分（U-4C-组分的Ugi反应）的变体。获得的化合物在最大电休克发作（MES）、皮下甲戊二氮（scMET）和最小阵挛发作（6 Hz）的癫痫动物模型中进行了抗惊厥活性评估。大部分衍生物在耐药性部分发作的6 Hz模型中的疗效明显高于传统的MES和scMET模型。最活性的化合物，(4R,8aR)-3a和(4S,8aS)-6在6 Hz测试中分别显示出中效剂量（ED50）为47.90和126.19 mg/kg。
• Synthesis of bicyclic 2,6-diketopiperazines via a three-step sequence involving an Ugi five-center, four-component reaction
  作者：Maciej Dawidowski、Franciszek Herold、Marcin Wilczek、Jadwiga Turło、Andrzej Chodkowski、Anna Gomółka、Jerzy Kleps

  DOI：10.1016/j.tet.2012.07.064

  日期：2012.9

  A three-step sequence involving an Ugi five-center, four-component reaction (U-5C-4CR), amide N-detertbutylation and cyclocondensation has been developed for easy access to diverse bicyclic 2,6-diketopiperazine (2,6-DKP) derivatives. In the key step, aromatic aldehydes were successfully coupled with cyclic alpha-amino acids and isocyanides in the course of U-5C-4CR. Boron trifluoride-acetic acid complex was developed as a new N-detertbutylating agent effective at rt. (C) 2012 Elsevier Ltd. All rights reserved.
• The synthesis and conformational analysis of optical isomers of 4-phenyl-perhydropyrido[1,2-a]pyrazine-1,3-dione: an example of ‘solid state–frozen’ dynamics in nitrogen-bridged bicyclic 2,6-diketopiperazines
  作者：Maciej Dawidowski、Franciszek Herold、Marcin Wilczek、Jerzy Kleps、Irena Wolska、Jadwiga Turło、Andrzej Chodkowski、Paweł Widomski、Anna Bielejewska

  DOI：10.1016/j.tetasy.2009.06.022

  日期：2009.8

  The synthesis, chemical properties, and conformational analysis of enantiopure (4R,9aS)-, (4S,9aR)-, (4S,9aS)-, and (4R,9aR)-4-phenyl-perhydropyrido[1,2-a]pyrazine-1,3-diones having potential biological activity are described. An interesting example of the coexistence of two invertomers of the (4R,9aR)-diastereomer in a single crystal unit cell is reported. The invertomers differ in the cis/trans-relationship between the fused rings and in the absolute configuration at the chiral nitrogen atom. The structure and equilibrium distributions of the respective conformers have been determined by NMR spectroscopy in both polar and non-polar solvents at various temperatures. The NMR spectra show that dynamic processes in the imide parts of the interconverting species are restrained by self-aggregation. The (4S,9aR)-diastereomer exists in a single conformation with insignificant dynamic effects. (c) 2009 Elsevier Ltd. All rights reserved.
• Synthesis and anticonvulsant activity of novel 2,6-diketopiperazine derivatives. Part 1: Perhydropyrrole[1,2-a]pyrazines
  作者：Maciej Dawidowski、Franciszek Herold、Andrzej Chodkowski、Jerzy Kleps、Paweł Szulczyk、Marcin Wilczek

  DOI：10.1016/j.ejmech.2011.07.027

  日期：2011.10

  A number of novel pyrrole[1,2-a]pyrazine derivatives were synthesized and evaluated in in vivo animal models of epilepsy. Among them, several compounds displayed promising seizure protection in the maximal electroshock seizure (MES), subcutaneous metrazol seizure (scMET), 6 Hz and pilocarpine-induced status prevention (PISP) tests, with ED50 values comparable to the reference anticonvulsant drugs (AEDs)

  合成了许多新颖的吡咯[1,2- a ]吡嗪衍生物，并在癫痫的体内动物模型中进行了评估。其中，几种化合物在最大电击惊厥（MES），皮下甲硝唑惊厥（scMET），6 Hz和毛果芸香碱引起的状态预防（PISP）测试中显示出有希望的癫痫保护作用，其ED 50值可与参考抗惊厥药（AEDs）相提并论。 ）。观察到吡咯[1,2- a ]吡嗪核心的立体化学和构象偏好对体内药理活性的关键影响。合成药物的抗惊厥作用机制很可能不是通过抑制电压依赖性钠（Na+）电流。
• The synthesis of new diastereomers of (4S,8aS)- and (4R,8aS)-4-phenyl-perhydropyrrole[1,2-a]pyrazine-1,3-dione
  作者：Franciszek Herold、Maciej Dawidowski、Irena Wolska、Andrzej Chodkowski、Jerzy Kleps、Jadwiga Turło、Andrzej Zimniak

  DOI：10.1016/j.tetasy.2007.08.025

  日期：2007.9

  The synthesis of new (4S,8aS)- and (4R,8aS)-4-phenyl-perhydropyrrole[1,2-a]pyrazine-1,3-diones in the cyclocondensation reaction of the respective derivatives of L-prolineamide is described. The effect of the amount of NaOEt, temperature, and reaction time on the proportions of diastereomers formed in the cyclocondensation reaction was examined. The structures of the diastercomers were confirmed by GC/MS, FIRMS, HPLC; XRD, and H-1 and C-13 NMR investigations. (C) 2007 Elsevier Ltd. All rights reserved.