tert-butyl (S)-2,5-dihydro-2,5-dioxo-1-methyl-α-<(tert-butoxycarbonyl)amino>pyrrole-3-propanoate | 144347-41-1

• 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: tert-butyl (S)-2,5-dihydro-2,5-dioxo-1-methyl-α-<(tert-butoxycarbonyl)amino>pyrrole-3-propanoate
• 英文别名: tert-butyl (S)-2-((tert-butoxycarbonyl)amino)-3-(1-methyl-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl)propanoate；tert-Butyl (S)-2,5-Dihydro-2,5-dioxo-1-methyl-α-[(tertbutoxycarbonyl)amino]pyrrole-3-propanoate；tert-Butyl (S)-2,5-Dihydro-2,5-dioxo-1-methyl-alpha-[(tertbutoxycarbonyl)amino]pyrrole-3-propanoate；tert-butyl (2S)-3-(1-methyl-2,5-dioxopyrrol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• CAS: 144347-41-1
• 化学式: C₁₇H₂₆N₂O₆
• 分子量: 354.403
• InChiKey: FCHWROLBYNLELZ-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-2,5-dihydro-2,5-dioxo-1-methyl-α-<(tert-butoxycarbonyl)amino>pyrrole-3-propanoate 在 ice 、 水 作用下， 以 三氟乙酸 为溶剂， 反应 32.0h， 以to give 0.33 g (59%) of 3 as a white solid的产率得到(S)-2,5-Dihydro-2,5-dioxo-α-amino-1-methylpyrrole-3-propanoic acid
  参考文献：
  名称：

  Bioactive quisqualic acid analogs

  摘要：

  本发明提供了通式为： ##STR1## 其中 R 为 H、(C.sub.1 -C.sub.4)烷基、(C.sub.3 -C.sub.6)环烷基、(C.sub.3 -C.sub.6)环烷基(C.sub.1 -C.sub.4)烷基、烯丙基、(C.sub.6 -C.sub.10)芳基或(C.sub.1 -C.sub.4)烷基CO.sub.2 Y；Y 为 H、(C.sub.1 -C.sub.4)烷基或(C.sub.6 -C.sub.10)芳基；每个 X 分别为 H、(C.sub.1 -C.sub.4)烷基、(C.sub.6 -C.sub.10)芳基、(C.sub.3 -C.sub.6)环烷基(C.sub.1 -C.sub.4)烷基或(C.sub.3 -C.sub.6)环烷基；由--表示的键存在或不存在；以及其药学上可接受的盐，并且使用该化合物刺激哺乳动物神经系统中的受体的方法。

  公开号：

  US05359087A1
• 作为产物：
  描述：

  1-O-tert-butyl 4-O-(2-sulfanylidenepyridin-1-yl) (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanedioate 在 MPCBA 作用下， 以 四氢呋喃 、 氯仿 、 甲苯 为溶剂， 反应 3.0h， 生成 tert-butyl (S)-2,5-dihydro-2,5-dioxo-1-methyl-α-<(tert-butoxycarbonyl)amino>pyrrole-3-propanoate
  参考文献：
  名称：

  Quisqualic acid analogs: synthesis of .beta.-heterocyclic 2-aminopropanoic acid derivatives and their activity at a novel quisqualate-sensitized site

  摘要：

  Hippocampal CA1 pyramidal cell neurons are sensitized over 30-fold to depolarization by L-2-amino-4-phosphonobutanoic acid (L-AP4) following exposure to L-quisqualic acid. This phenomenon has been termed the QUIS effect. In the present study several novel L-quisqualic acid analogues have been synthesized and tested for their interaction with the different components of the QUIS-effect system. Replacement of the oxadiazolidinedione ring Of L-quisqualic acid with several other types of heterocyclic rings yielded the following quisqualic acid analogues: maleimide 2, N-methylmaleimide 3, N-(carboxymethyl)maleimide 4, succinimides 5A and 5B, and imidazolidinedione 6. None of these analogues were able to mimic the effects Of L-quisqualic acid and sensitize hippocampal CA1 neurons to depolarization by L-AP4. Also, unlike L-serine O-sulfate, L-homocysteinesulfinic acid, or L-alpha-aminoadipic acid, none of the analogues were able to preblock or reverse the QUIS effect. However, when the IC50 values for inhibition of the CA1 synaptic field potential of analogues 2-6 were determined both before and after hippocampal slices were exposed to L-quisqualic acid, the IC50 values of analogues 3 and 4 were found to decrease more than 7-fold. Thus, these two compounds behave like L-AP4 rather than L-quisqualic acid in this system in that they exhibit increased potencies in slices that have been pretreated with L-quisqualic acid even though they cannot themselves induce this sensitization. Compounds 3 and 4, therefore, represent the first non-phosphorus-containing compounds to which hippocampal neurons become sensitized following exposure to L-quisqualic acid. No change in the IC50 values was observed for 5A or 5B. Analogues 2 and 6, on the other hand, displayed a high potency for inhibition of the evoked field potential even prior to treatment of the slices with L-quisqualic acid.

  DOI：

  10.1021/jm00102a014

文献信息

• New 4-Functionalized Glutamate Analogues Are Selective Agonists at Metabotropic Glutamate Receptor Subtype 2 or Selective Agonists at Metabotropic Glutamate Receptor Group III
  作者：Tri H. V. Huynh、Mette N. Erichsen、Amélie S. Tora、Cyril Goudet、Emmanuelle Sagot、Zeinab Assaf、Christian Thomsen、Robb Brodbeck、Tine B. Stensbøl、Walden E. Bjørn-Yoshimoto、Birgitte Nielsen、Jean-Philippe Pin、Thierry Gefflaut、Lennart Bunch

  DOI：10.1021/acs.jmedchem.5b01333

  日期：2016.2.11

  core scaffold led to the stereoselective synthesis of four new conformationally restricted Glu analogues, 2a–d. Most interestingly, 2a retained a selective agonist activity profile at mGlu2 (EC50 in the micromolar range), whereas 2c/2d were both selective agonists at group III, subtypes mGlu4,6,8. In general, 2d was 20-fold more potent than 2c and potently activated mGlu4,6,8 in the low–mid nanomolar

  代谢型谷氨酸（Glu）受体（mGluRs）在调节大脑兴奋性神经传递中起关键作用。总共确定了八种亚型，并将其分为三组，第一组（mGlu1,5），第二组（mGlu2,3）和第三组（mGlu4,6-8）。在本文中，我们介绍了一个L-2,4-syn-取代的Glu类似物1d，它在mGlu2上显示了对其余mGluR亚型的选择性激动剂活性。对核心支架的建模研究和重新设计导致了四个新的构象受限的Glu类似物2a - d的立体选择性合成。最有趣的是，2a在mGlu2（EC 50在微摩尔范围内）保留了选择性激动剂活性谱，而2c /2d均为第III组mGlu4、6、8亚型的选择性激动剂。通常，在低-中纳摩尔范围内，2d的效力比2c强20倍，并且有效活化了mGlu4、6、8。