(3S,6S)-3-phenylmethyl-6-(amidocarbonylmethyl)piperazine-2,5-dione | 55881-18-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3S,6S)-3-phenylmethyl-6-(amidocarbonylmethyl)piperazine-2,5-dione
• 英文别名: 2-((2S,5S)-5-benzyl-3,6-dioxopiperazin-2-yl)acetamide；cyclo(L-asparaginyl-L-phenylalanyl)；cis-cyclo(Asn-Phe)；cyclo(Asn-Phe)；2-(5-benzyl-3,6-dioxo-piperazin-2-yl)-acetamide；2-[(2S,5S)-5-benzyl-3,6-dioxopiperazin-2-yl]acetamide
• CAS: 55881-18-0
• 化学式: C₁₃H₁₅N₃O₃
• 分子量: 261.28
• InChiKey: PBPWMUZEJODEEP-UWVGGRQHSA-N

物化性质

• 沸点：
  707.4±45.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3S,6S)-3-phenylmethyl-6-(amidocarbonylmethyl)piperazine-2,5-dione 在 三氟化硼四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 反应 40.0h， 以80.9%的产率得到2-[(2S,5S)-5-benzylpiperazin-2-yl]ethylamine
  参考文献：
  名称：

  The 5-substituted piperazine as a novel secondary pharmacophore greatly improving the physical properties of urea-based inhibitors of soluble epoxide hydrolase

  摘要：

  The inhibition of the mammalian soluble epoxide hydrolase (sEH) is a promising new therapy in the treatment of hypertention and inflammation. The problems of limited water solubility and high melting points commonly displayed by the active 1,3-disubstituted ureas prevent the further development of potent urea-based sEH inhibitors. Therefore, a new class of potent inhibitors of sEH were designed and synthesized by the introduction of a polar constrained piperazino group in the right side of adasmantyl urea to increase the water solubility. A facile and general synthesis was established to prepare a series of 1-adamantan-1-yl-3-(2-piperazin-2-yl-ethyl)-ureas (1a-d) with various 5-substitutions on the 2-piperazino ring, which will advance the SAR study by the efficient making of structurally diverse analogs. The effect of the 5-substitution on the activity and the water solubility was examined. The best potency was exhibited by the 5-benzyl-substituted-piperazine-containing urea with an IC50 value of 1.37 mu M against human sEH and good water solubility (S = 7.46 mg/mL) and low melting point, in which the 5-substituted piperazine serves as a favorable secondary pharmacophore and a water-solubility enhancing group. Our present work provides a promising new template for the design of orally available therapeutic agents for the disorders that can be addressed by changing the in vivo concentration of the chemical mediators that contain an epoxide. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.06.005
• 作为产物：
  描述：

  asparaginyl-phenylalanine methyl ester 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以1.08 mmol的产率得到(3S,6S)-3-phenylmethyl-6-(amidocarbonylmethyl)piperazine-2,5-dione
  参考文献：
  名称：

  Structures, Sensory Activity, and Dose/Response Functions of 2,5-Diketopiperazines in Roasted Cocoa Nibs (Theobroma cacao)

  摘要：

  The taste compounds inducing the blood-like, metallic bitter taste sensation reported recently for a dichloromethane extract prepared from roasted cocoa nibs were identified as a series of 25 diketopiperazines by means of HPLC degustation, LC-MS/MS, and independent synthesis. Among these 25 compounds, 13 cis-configured diketopiperazines, namely, CYCIO(L-IIe-L-Phe), CYCIO(L-Val-L-Leu), CYCIO(L-Pro-L-Pro), CYCIO(L-IIe-L-Pro), CYCIO(L-Val-L-Tyr), CYCIO(L-Ala-L-Tyr), CYCIO(L-Phe-L-Ser), CYCIO(L-Ala-L-IIe), CYCIO(L-LeU-L-Phe), cyclo(L-Pro-L-Val), CYCIO(L-Pro-L-Thr), CYCIO(L-PrO-L-Tyr), and CYCIO(L-Val-L-Val) were identified for the first time in cocoa. In addition, the taste recognition thresholds for the metallic as well as the bitter taste of the diketopiperazines were determined, and after quantitative analysis by using two diastereomeric diketopiperazines as the internal standards, the sensory impact of the diketopiperazines was evaluated on the basis of their close-over-threshold (DoT) factors calculated as the ratio of the concentration and the threshold concentration of a compound. These data revealed DoT factors above 1.0 exclusively for cis-cyclo(L-Pro-L-Val), cis-cyclo(L-Val-L-Leu), cis-cyclo(L-Ala-L-IIe), cis-cyclo(L-Ala-L-Leu), and cis-cyclo(L-IIe-L-Pro), whereas all of the other diketopiperazines were present below their individual bitter taste threshold concentrations and should therefore not contribute to the cocoa taste. Because the DoT factors do not consider the nonlinear relationship between the concentration and gustatory response of an individual compound, we, for the first time, report on the recording of dose/response functions describing the human bitter taste perception of diketopiperazines more precisely.

  DOI：

  10.1021/jf051313m

文献信息

• Synthesis of Fluorescent Gelators and Direct Observation of Gelation with a Fluorescence Microscope
  作者：Kenji Hanabusa、Takuya Ueda、Shingo Takata、Masahiro Suzuki

  DOI：10.1002/chem.201603295

  日期：2016.11.14

  and trans‐(1R,2R)‐diaminocyclohexane. The emission behaviors of the gelators were investigated, and their gelation abilities studied against 15 solvents. The minimum gel concentration, variable‐temperature spectroscopy, transmission electron microscopy, scanning electron microscopy, fluorescence microscopy (FM), and confocal laser scanning microscopy (CLSM) were used to characterize gelation. The intermolecular

  荧光素，苯并噻唑，喹啉，stilbene-，和含咔唑的荧光胶凝剂已经通过连接胶凝驱动段，包括合成的升-异亮氨酸，升-缬氨酸，升-苯丙氨酸，升-亮氨酸残基，环（升-天冬酰胺基-1-苯丙氨酰基）和反式-（1 R，2 R）-二氨基环己烷 研究了胶凝剂的发射行为，并研究了它们对15种溶剂的胶凝能力。最低凝胶浓度，可变光谱，透射电子显微镜，扫描电子显微镜，荧光显微镜（FM）和共聚焦激光扫描显微镜（CLSM）用于表征凝胶化。NH和C = O之间的分子间氢键，范德华相互作用和π–π堆积在胶凝中起重要作用。发射的颜色与胶凝剂的荧光结构有关。FM观察到以其发射颜色为特征的纤维聚集体。通过每0.1μm的CLSM捕获的图像叠加到固定深度即可生成3D图像。3D图像显示，微米级的大聚集体沿三维分布。对混合胶凝剂的FM观察进行了研究。在胶凝的情况下，具有相同胶凝驱动链段的两个结构相关的胶凝剂会导致胶凝剂通过相似的氢键
• Fluorescent Gelators for Detection of Explosives
  作者：Kenji Hanabusa、Shingo Takata、Masafumi Fujisaki、Yasushi Nomura、Masahiro Suzuki

  DOI：10.1246/bcsj.20160232

  日期：2016.11.15

  Carbazole-, quinoline-, benzothiazole-, and stilbene-containing fluorescent gelators are synthesized by connecting gelation-driving segments, and their gelation abilities are studied with 13 solvents. Fibrous thin-layer films are prepared on quartz plates from the solutions or gels, and they are studied as chemosensors for explosives. Fluorescence quenching of the films upon exposure to saturated TNT or RDX vapor is used to evaluate the abilities of the films to detect explosives. The relationship between the thickness of the thin-layer film and the quenching efficiency upon exposure to TNT is studied. The morphologies of the thin-layer films are observed by dynamic force mode scanning probe microscopy and discussed with regard to their fluorescence quenching. The interactions among chromophores in the gels, thin-layer films, and solutions are studied by variable-temperature spectroscopy. The mechanism of TNT detection is discussed from the viewpoint of the HOMO and LUMO energy levels.

  合成了含有氮杂环、喹啉、苯并噻唑和苯乙烯的荧光凝胶剂，通过连接促使凝胶化的片段，并使用13种溶剂研究它们的凝胶能力。在石英板上从溶液或凝胶中制备了纤维状薄膜，并将其作为化学传感器用于探测爆炸物。薄膜在接触饱和的TNT或RDX蒸气时的荧光淬灭被用来评估薄膜检测爆炸物的能力。研究了薄层膜厚度与接触TNT时淬灭效率之间的关系。通过动态力模式扫描探针显微镜观察薄层膜的形态，并讨论其与荧光淬灭的关系。通过可变温光谱学研究凝胶、薄层膜和溶液中色谱体之间的相互作用。从HOMO和LUMO能级的角度讨论了TNT检测机制。
• Structures, Sensory Activity, and Dose/Response Functions of 2,5-Diketopiperazines in Roasted Cocoa Nibs (<i>Theobroma cacao</i>)
  作者：Timo Stark、Thomas Hofmann

  DOI：10.1021/jf051313m

  日期：2005.9.1

  The taste compounds inducing the blood-like, metallic bitter taste sensation reported recently for a dichloromethane extract prepared from roasted cocoa nibs were identified as a series of 25 diketopiperazines by means of HPLC degustation, LC-MS/MS, and independent synthesis. Among these 25 compounds, 13 cis-configured diketopiperazines, namely, CYCIO(L-IIe-L-Phe), CYCIO(L-Val-L-Leu), CYCIO(L-Pro-L-Pro), CYCIO(L-IIe-L-Pro), CYCIO(L-Val-L-Tyr), CYCIO(L-Ala-L-Tyr), CYCIO(L-Phe-L-Ser), CYCIO(L-Ala-L-IIe), CYCIO(L-LeU-L-Phe), cyclo(L-Pro-L-Val), CYCIO(L-Pro-L-Thr), CYCIO(L-PrO-L-Tyr), and CYCIO(L-Val-L-Val) were identified for the first time in cocoa. In addition, the taste recognition thresholds for the metallic as well as the bitter taste of the diketopiperazines were determined, and after quantitative analysis by using two diastereomeric diketopiperazines as the internal standards, the sensory impact of the diketopiperazines was evaluated on the basis of their close-over-threshold (DoT) factors calculated as the ratio of the concentration and the threshold concentration of a compound. These data revealed DoT factors above 1.0 exclusively for cis-cyclo(L-Pro-L-Val), cis-cyclo(L-Val-L-Leu), cis-cyclo(L-Ala-L-IIe), cis-cyclo(L-Ala-L-Leu), and cis-cyclo(L-IIe-L-Pro), whereas all of the other diketopiperazines were present below their individual bitter taste threshold concentrations and should therefore not contribute to the cocoa taste. Because the DoT factors do not consider the nonlinear relationship between the concentration and gustatory response of an individual compound, we, for the first time, report on the recording of dose/response functions describing the human bitter taste perception of diketopiperazines more precisely.
• The 5-substituted piperazine as a novel secondary pharmacophore greatly improving the physical properties of urea-based inhibitors of soluble epoxide hydrolase
  作者：Hui-Yuan Li、Yi Jin、Christophe Morisseau、Bruce D. Hammock、Ya-Qiu Long

  DOI：10.1016/j.bmc.2006.06.005

  日期：2006.10

  The inhibition of the mammalian soluble epoxide hydrolase (sEH) is a promising new therapy in the treatment of hypertention and inflammation. The problems of limited water solubility and high melting points commonly displayed by the active 1,3-disubstituted ureas prevent the further development of potent urea-based sEH inhibitors. Therefore, a new class of potent inhibitors of sEH were designed and synthesized by the introduction of a polar constrained piperazino group in the right side of adasmantyl urea to increase the water solubility. A facile and general synthesis was established to prepare a series of 1-adamantan-1-yl-3-(2-piperazin-2-yl-ethyl)-ureas (1a-d) with various 5-substitutions on the 2-piperazino ring, which will advance the SAR study by the efficient making of structurally diverse analogs. The effect of the 5-substitution on the activity and the water solubility was examined. The best potency was exhibited by the 5-benzyl-substituted-piperazine-containing urea with an IC50 value of 1.37 mu M against human sEH and good water solubility (S = 7.46 mg/mL) and low melting point, in which the 5-substituted piperazine serves as a favorable secondary pharmacophore and a water-solubility enhancing group. Our present work provides a promising new template for the design of orally available therapeutic agents for the disorders that can be addressed by changing the in vivo concentration of the chemical mediators that contain an epoxide. (c) 2006 Elsevier Ltd. All rights reserved.