3-乙基-1,3-二甲基-2,5-吡咯烷二酮 | 13861-99-9

• 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
• 中文名称: 3-乙基-1,3-二甲基-2,5-吡咯烷二酮
• 英文名称: 2,5-pyrrolidinedione, 3-ethyl-1,3-dimethyl-
• 英文别名: 3-ethyl-1,3-dimethyl-2,5-pyrrolidinedione；3-ethyl-1,3-dimethyl-pyrrolidine-2,5-dione；3-Aethyl-1,3-dimethyl-pyrrolidin-2,5-dion；2-Ethyl-2-methyl-N-methyl-succinimid；2-Ethyl-2,N-dimethyl-succinimid；3-ethyl-1,3-dimethylpyrrolidine-2,5-dione
• CAS: 13861-99-9
• 化学式: C₈H₁₃NO₂
• 分子量: 155.197
• InChiKey: SZXUVNXLZXDSLJ-UHFFFAOYSA-N

物化性质

• 保留指数：
  1416

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 生成 3-乙基-1,3-二甲基-2,5-吡咯烷二酮
  参考文献：
  名称：

  Anticonvulsants. III. A Study of N,α,β-Alkylsuccinimides

  摘要：

  DOI：

  10.1021/ja01098a034

文献信息

• α-Methyl-α-phenylsuccinimide ameliorates neurodegeneration in a C. elegans model of TDP-43 proteinopathy
  作者：Shi Quan Wong、Matthew G. Pontifex、Marie M. Phelan、Chandra Pidathala、Brian C. Kraemer、Jeff W. Barclay、Neil G. Berry、Paul M. O'Neill、Robert D. Burgoyne、Alan Morgan

  DOI：10.1016/j.nbd.2018.06.013

  日期：2018.10

  The antiepileptic drug ethosuximide has recently been shown to be neuroprotective in various Caenorhabditis elegans and rodent neurodegeneration models. It is therefore a promising repurposing candidate for the treatment of multiple neurodegenerative diseases. However, high concentrations of the drug are required for its protective effects in animal models, which may impact on its translational potential and impede the identification of its molecular mechanism of action. Therefore, we set out to develop more potent neuroprotective lead compounds based on ethosuximide as a starting scaffold. Chemoinformatic approaches were used to identify compounds with structural similarity to ethosuximide and to prioritise these based on good predicated blood brain barrier permeability and C. elegans bioaccumulation properties. Selected compounds were initially screened for anti-convulsant activity in a C. elegans pentylenetetrazol-induced seizure assay, as a rapid primary readout of bioactivity; and then assessed for neuroprotective properties in a C. elegans TDP-43 proteinopathy model based on pan-neuronal expression of human A315T mutant TDP-43. The most potent compound screened, a-methyl-a-phenylsuccinimide (MPS), ameliorated the locomotion defects and extended the shortened lifespan of TDP-43 mutant worms. MPS also directly protected against neurodegeneration by reducing the number of neuronal breaks and cell body losses in GFP-labelled GABAergic motor neurons. Importantly, optimal neuroprotection was exhibited by external application of 50 mu M MPS, compared to 8 mM for ethosuximide. This greater potency of MPS was not due to bioaccumulation to higher internal levels within the worm, based on H-1-nuclear magnetic resonance analysis. Like ethosuximide, the activity of MPS was abolished by mutation of the evolutionarily conserved FOXO transcription factor, daf-16, suggesting that both compounds act via the same neuroprotective pathway(s).In conclusion, we have revealed a novel neuroprotective activity of MPS that is > 100-fold more potent than ethosuximide. This increased potency will facilitate future biochemical studies to identify the direct molecular target(s) of both compounds, as we have shown here that they share a common downstream DAF-16-dependent mechanism of action. Furthermore, MPS is the active metabolite of another approved antiepileptic drug, methsuximide. Therefore, methsuximide may have repurposing potential for treatment of TDP-43 proteinopathies and possibly other human neurodegenerative diseases.
• Multi-API Loading Prodrugs
  申请人：Alkermes Pharma Ireland Limited

  公开号：US20160024011A1

  公开（公告）日：2016-01-28

  The present invention accomplishes this by having multiple molecules of parent drugs attached to carrier moieties and by extending the period during which the parent drug is released and absorbed after administration to the patient and providing a longer duration of action per dose than the parent drug itself. Prodrug conjugates are suitable for sustained delivery of heteroaryl, lactam-amide-, imide-, sulfonamide-, carbamate-, urea-, benzamide-, acylaniline-, cyclic amide- and tertiary amine-containing parent drugs that are substituted at the amide nitrogen or oxygen atom with labile aldehyde-linked prodrug moieties. The carrier groups of the prodrugs can be hydrophobic to reduce the polarity and solubility of the parent drug under physiological conditions.
• Anticonvulsants. III. A Study of N,α,β-Alkylsuccinimides
  作者：C. A. Miller、Loren M. Long

  DOI：10.1021/ja01098a034

  日期：1953.1