(3S,6R,7aR)-6-((S)-1,4-Dioxo-hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-5-oxo-hexahydro-pyrrolo[2,1-b]thiazole-3-carboxylic acid methyl ester | 197453-41-1

• 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,6R,7aR)-6-((S)-1,4-Dioxo-hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-5-oxo-hexahydro-pyrrolo[2,1-b]thiazole-3-carboxylic acid methyl ester
• 英文别名: methyl (3S,6R,7aR)-6-[(8aS)-1,4-dioxo-6,7,8,8a-tetrahydro-3H-pyrrolo[1,2-a]pyrazin-2-yl]-5-oxo-3,6,7,7a-tetrahydro-2H-pyrrolo[2,1-b][1,3]thiazole-3-carboxylate
• CAS: 197453-41-1
• 化学式: C₁₅H₁₉N₃O₅S
• 分子量: 353.399
• InChiKey: YZAHSZHMPIBEPC-BTQIBKBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  113
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3S,6R,7aR)-6-((S)-1,4-Dioxo-hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-5-oxo-hexahydro-pyrrolo[2,1-b]thiazole-3-carboxylic acid methyl ester 在 氨 作用下， 以 甲醇 为溶剂， 反应 5.0h， 生成 6-((S)-1,4-Dioxo-hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-5-oxo-hexahydro-pyrrolo[2,1-b]thiazole-3-carboxylic acid amide 、 (3S,6R,7aR)-6-((S)-1,4-Dioxo-hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-5-oxo-hexahydro-pyrrolo[2,1-b]thiazole-3-carboxylic acid amide 、 (3S,6S,7aR)-6-((S)-1,4-Dioxo-hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-5-oxo-hexahydro-pyrrolo[2,1-b]thiazole-3-carboxylic acid amide
  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：

  L-脯氨酸叔丁酯 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 33.25h， 生成 (3S,6R,7aR)-6-((S)-1,4-Dioxo-hexahydro-pyrrolo[1,2-a]pyrazin-2-yl)-5-oxo-hexahydro-pyrrolo[2,1-b]thiazole-3-carboxylic 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

文献信息

• Design, Synthesis, and Dopamine Receptor Modulating Activity of Diketopiperazine Peptidomimetics of <scp>l</scp>-Prolyl-<scp>l</scp>-leucylglycinamide
  作者：Paul W. Baures、William H. Ojala、Willard J. Costain、Michael C. Ott、Ashish Pradhan、William B. Gleason、Ram K. Mishra、Rodney L. Johnson

  DOI：10.1021/jm970328b

  日期：1997.10.1

  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.