[(S)-2-((S)-1,4-Dioxo-hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-4-methyl-pentanoylamino]-acetic acid methyl ester | 197453-31-9

• 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: [(S)-2-((S)-1,4-Dioxo-hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-4-methyl-pentanoylamino]-acetic acid methyl ester
• CAS: 197453-31-9
• 化学式: C₁₆H₂₅N₃O₅
• 分子量: 339.392
• InChiKey: SSBVOTQQZLRIHB-RYUDHWBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.48
• 重原子数：
  24.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  96.02
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  [(S)-2-((S)-1,4-Dioxo-hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-4-methyl-pentanoylamino]-acetic acid methyl ester 在 氨 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以100%的产率得到(2S)-2-[(8aS)-1,4-dioxo-6,7,8,8a-tetrahydro-3H-pyrrolo[1,2-a]pyrazin-2-yl]-N-(2-amino-2-oxoethyl)-4-methylpentanamide
  参考文献：
  名称：

  Design, Synthesis, and Dopamine Receptor Modulating Activity of Diketopiperazine Peptidomimetics of l-Prolyl-l-leucylglycinamide

  摘要：

  The diketopiperazine ''C5'' conformational mimic has been incorporated into the L-prolyl-L-leucylglycinamide (PLG,1) structure and into the bicyclic lactam PLG peptidomimetic structure 3 to give compounds 5 and 6, respectively. These analogues were designed to explore the idea that the N-terminal ''C5'' conformation, which was found in the crystal structure of 2 and which was mimicked in 4 by the diketopiperazine function, was a factor in the high potency of these two agents. Through the use of the [H-3]spiroperidol/N-propylnorapomorphine (NPA) D-2 receptor competitive binding assay, both 5 and 6 were found to increase the affinity of the dopamine receptor for agonists and both were found to increase the percentage of D-2 receptors which existed in the high-affinity state. These effects were observed when Gpp(NH)p was either absent or present, and they were analogous to the effects observed previously for PLG and the PLG peptidomimetics 2 and 4. However, the potency seen with 5 and 6 was less than that seen for 2 and 4, suggesting that while the N-terminal ''C5'' conformation may play a role in the potency of the gamma-lactam peptidomimetics of PLG, it does not appear to be the primary factor. In the 6-hydroxydopamine-lesioned animal model of Parkinson's disease, 5 altered apomorphine-induced rotational behavior in a dose-dependent manner. The maximum effect occurred at a dose of 0.01 mg/kg ip and resulted in a 52.27 +/- 13.96% (p < 0.001, n = 7) increase in rotations compared to apomorphine administered alone.

  DOI：

  10.1021/jm970328b
• 作为产物：
  描述：

  N-chloroacetyl-L-proline methyl ester 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 乙二醇乙醚 、 二氯甲烷 为溶剂， 反应 88.0h， 生成 [(S)-2-((S)-1,4-Dioxo-hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-4-methyl-pentanoylamino]-acetic acid methyl ester
  参考文献：
  名称：

  Design, Synthesis, and Dopamine Receptor Modulating Activity of Diketopiperazine Peptidomimetics of l-Prolyl-l-leucylglycinamide

  摘要：

  The diketopiperazine ''C5'' conformational mimic has been incorporated into the L-prolyl-L-leucylglycinamide (PLG,1) structure and into the bicyclic lactam PLG peptidomimetic structure 3 to give compounds 5 and 6, respectively. These analogues were designed to explore the idea that the N-terminal ''C5'' conformation, which was found in the crystal structure of 2 and which was mimicked in 4 by the diketopiperazine function, was a factor in the high potency of these two agents. Through the use of the [H-3]spiroperidol/N-propylnorapomorphine (NPA) D-2 receptor competitive binding assay, both 5 and 6 were found to increase the affinity of the dopamine receptor for agonists and both were found to increase the percentage of D-2 receptors which existed in the high-affinity state. These effects were observed when Gpp(NH)p was either absent or present, and they were analogous to the effects observed previously for PLG and the PLG peptidomimetics 2 and 4. However, the potency seen with 5 and 6 was less than that seen for 2 and 4, suggesting that while the N-terminal ''C5'' conformation may play a role in the potency of the gamma-lactam peptidomimetics of PLG, it does not appear to be the primary factor. In the 6-hydroxydopamine-lesioned animal model of Parkinson's disease, 5 altered apomorphine-induced rotational behavior in a dose-dependent manner. The maximum effect occurred at a dose of 0.01 mg/kg ip and resulted in a 52.27 +/- 13.96% (p < 0.001, n = 7) increase in rotations compared to apomorphine administered alone.

  DOI：

  10.1021/jm970328b