2-(1,4-dioxooctahydropyrrolo<1,2-a>pyrazin-3-yl)ethanamide | 55881-17-9

• 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: 2-(1,4-dioxooctahydropyrrolo<1,2-a>pyrazin-3-yl)ethanamide
• 英文别名: 2-((3S,8aS)-1,2-dioxooctahydropyrrolo[1,2-a]pyrazin-3-yl)acetamide；3-carbamoylmethylhexahydropyrrolo[1,2-a]pyrazin-1,4-dione；cyclo-Asn-Pro；cyclo-L-Asn-L-Pro；2-[(3S,8aS)-1,4-dioxo-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-3-yl]acetamide
• CAS: 55881-17-9
• 化学式: C₉H₁₃N₃O₃
• 分子量: 211.221
• InChiKey: SMWQCKMKPDUGIZ-WDSKDSINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  92.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(1,4-dioxooctahydropyrrolo<1,2-a>pyrazin-3-yl)ethanamide 在 三氟化硼四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 以80.9%的产率得到2-((3S,8aS)-octahydropyrrolo[1,2-a]pyrazin-3-yl)acetamide
  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：

  L-脯氨酰胺 在 盐酸 、 1-羟基苯并三唑 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-(1,4-dioxooctahydropyrrolo<1,2-a>pyrazin-3-yl)ethanamide
  参考文献：
  名称：

  强制置换和构象限制对甲状腺激素类似物的精神活性的影响

  摘要：

  在三肽 Glp-Gln-Pro 的合成中观察到 Gln(Asn)-Pro-NH2 容易内酰胺化，形成具有二酮哌嗪结构的环状二肽（具有 X-Protrans 键的线性三肽的构象片段的模拟物） -NH2 通过在甲状腺激素（Glp-His-Pro-NH2，TRH）及其结构类似物 [Asn2]TRH 的合成中用必需的类似谷氨酰胺替换组氨酸来修饰。在合成的肽的质谱图中揭示了对应于 Glp 和 Pro 氨基酸残基的离子峰。测定所得化合物的生物学特性，表明强制置换导致 [Gln2]TRH 的生理特异性增加。

  DOI：

  10.1007/bf02494506

文献信息

• An efficient green synthesis of proline-based cyclic dipeptides under water-mediated catalyst-free conditions
  作者：Habeebullah Thajudeen、Kyungseok Park、Surk-Sik Moon、In Seok Hong

  DOI：10.1016/j.tetlet.2009.12.134

  日期：2010.3

  L-Proline-based cyclic dipeptides were synthesized from N-Boc-protected dipeptide methyl esters under catalyst-free condition using water as a solvent. One-pot deprotection and cyclization have been used is the key steps, providing an efficient and environmentally friendly approach. Clean reaction conditions, easy isolation, and good yields of cyclic dipeptides are the salient features of the proposed methodology (C) 2010 Elsevier Ltd All rights reserved.
• 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.
• Effect of obligatory replacement and conformational restriction on psychotropic activity of thyroliberin analogs
  作者：A. A. Mazurov、T. I. Korotenko、V. Ya. Gorbatyuk、Yu. E. Shapiro、A. V. Mazepa、A. I. Dyadenko、S. A. Andronati

  DOI：10.1007/bf02494506

  日期：1998.10

  obligatory replacement resulted in an increased physiological specificity of [Gln2]TRH. The enhanced activity of conformationally restricted cyclic peptides compared to linear ones suggests that the biologically active conformation responsible for the antidepressant activity of linear TRH analogs is the conformation with X−Protrans-bond.

  在三肽 Glp-Gln-Pro 的合成中观察到 Gln(Asn)-Pro-NH2 容易内酰胺化，形成具有二酮哌嗪结构的环状二肽（具有 X-Protrans 键的线性三肽的构象片段的模拟物） -NH2 通过在甲状腺激素（Glp-His-Pro-NH2，TRH）及其结构类似物 [Asn2]TRH 的合成中用必需的类似谷氨酰胺替换组氨酸来修饰。在合成的肽的质谱图中揭示了对应于 Glp 和 Pro 氨基酸残基的离子峰。测定所得化合物的生物学特性，表明强制置换导致 [Gln2]TRH 的生理特异性增加。