methyl (2S,5R,7R)-1-aza-7-[(tert-butoxycarbonyl)amino]-8-oxo-4-thiabicyclo[3.3.0]octane-2-carboxylate | 150507-47-4

• 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: methyl (2S,5R,7R)-1-aza-7-[(tert-butoxycarbonyl)amino]-8-oxo-4-thiabicyclo[3.3.0]octane-2-carboxylate
• 英文别名: methyl (3S,6R,7aR)-6-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxo-3,6,7,7a-tetrahydro-2H-pyrrolo[2,1-b][1,3]thiazole-3-carboxylate
• CAS: 150507-47-4
• 化学式: C₁₃H₂₀N₂O₅S
• 分子量: 316.378
• InChiKey: HZTSAZVICTZTNP-IWSPIJDZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (2S,5R,7R)-1-aza-7-[(tert-butoxycarbonyl)amino]-8-oxo-4-thiabicyclo[3.3.0]octane-2-carboxylate 在 盐酸 、 氨 、 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 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.0h， 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
  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：

  重氮甲烷 、 D-半胱氨酸盐酸盐 、 Boc-D-Asp(H)-OBzl 在 吡啶 、 4 A molecular sieve 作用下， 生成 methyl (2S,5R,7R)-1-aza-7-[(tert-butoxycarbonyl)amino]-8-oxo-4-thiabicyclo[3.3.0]octane-2-carboxylate 、 methyl (2S,5R,7S)-1-aza-7-<(tert-butoxycarbonyl)amino>-8-oxo-4-thiabicyclo<3.3.0>octane-2-carboxylate 、 methyl (2R,5S,7R)-1-aza-7-<(tert-butoxycarbonyl)amino>-8-oxo-4-thiabicyclo<3.3.0>octane-2-carboxylate
  参考文献：
  名称：

  多巴胺受体调节肽Pro-Leu-Gly-NH2的双环噻唑烷内酰胺肽模拟物。

  摘要：

  已经合成了双环噻唑烷内酰胺内拟肽3-5，作为多巴胺受体调节肽Pro-Leu-Gly-NH2（PLG）的潜在类似物。拟肽3和4被设计为将四个扭转角中的两个psi 2和phi 3约束为一个β-转角，使其接近于II型β-转角，而5被设计为一种化合物，可以无法实现β转弯构象。发现拟肽3和4增强多巴胺受体激动剂ADTN与多巴胺受体的结合，而发现5是无活性的。像PLG一样，3和4的剂量反应曲线实际上是钟形的，在浓度为1 microM时产生最大作用。3和4在增强ADTN与多巴胺受体的结合方面均比PLG更有效。5 5-双环噻唑烷内酰胺肽模拟物3将ADTN的结合提高了近200％，而6,5-双环噻唑烷内酰胺肽模拟物4将ADTN的结合提高了约75％。这些结果提供了进一步的证据，支持了PLG的生物活性构象是II型β转角的假说。

  DOI：

  10.1021/jm00068a013

文献信息

• Bicyclic thiazolidine lactam peptidomimetics of the dopamine receptor modulating peptide Pro-Leu-Gly-NH2
  作者：Nalin L. Subasinghe、Roger J. Bontems、Edward McIntee、Ram K. Mishra、Rodney L. Johnson

  DOI：10.1021/jm00068a013

  日期：1993.8

  achieve a beta-turn conformation. Peptidomimetics 3 and 4 were found to enhance the binding of the dopamine receptor agonist ADTN to the dopamine receptor, while 5 was found to be inactive. Like PLG the dose-response curves for 3 and 4 were bell-shaped in nature with the maximum effect occurring at a concentration of 1 microM. Both 3 and 4 were more effective than PLG in enhancing the binding of ADTN to

  已经合成了双环噻唑烷内酰胺内拟肽3-5，作为多巴胺受体调节肽Pro-Leu-Gly-NH2（PLG）的潜在类似物。拟肽3和4被设计为将四个扭转角中的两个psi 2和phi 3约束为一个β-转角，使其接近于II型β-转角，而5被设计为一种化合物，可以无法实现β转弯构象。发现拟肽3和4增强多巴胺受体激动剂ADTN与多巴胺受体的结合，而发现5是无活性的。像PLG一样，3和4的剂量反应曲线实际上是钟形的，在浓度为1 microM时产生最大作用。3和4在增强ADTN与多巴胺受体的结合方面均比PLG更有效。5 5-双环噻唑烷内酰胺肽模拟物3将ADTN的结合提高了近200％，而6,5-双环噻唑烷内酰胺肽模拟物4将ADTN的结合提高了约75％。这些结果提供了进一步的证据，支持了PLG的生物活性构象是II型β转角的假说。
• 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.