2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanoic acid | 30270-19-0

• 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: 2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanoic acid
• 英文别名: α-(Methylsuccinimido)-propionsaeure
• CAS: 30270-19-0
• 化学式: C₈H₁₁NO₄
• 分子量: 185.18
• InChiKey: QQIDCYIERBMXTC-UHFFFAOYSA-N

物化性质

• 沸点：
  417.4±28.0 °C(Predicted)
• 密度：
  1.327±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanoic acid 、 对三氟甲基苯胺 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 24.5h， 以55%的产率得到2-(3-methyl-2,5-dioxopyrrolidin-1-yl)-N-[4-(trifluoromethyl)phenyl]propanamide
  参考文献：
  名称：

  N-苯基-2-（2,5-二氧杂吡咯烷-1-基）-丙酰胺和-丁酰胺衍生的新型杂化化合物的设计，合成和抗惊厥活性

  摘要：

  重点研究了21种新的N-苯基-2-（2,5-二氧杂吡咯烷-1-基）丙酰胺，2-（3-甲基-2,5-二氧杂吡咯烷-1-基）丙酰胺和2-（2，合成了5-二氧杂吡咯烷-1-基）丁酰胺衍生物作为潜在的新型杂化抗惊厥药。这些杂合分子是作为先前描述的N-苄基衍生物的紧密类似物获得的，并且融合了临床上相关的抗癫痫药如乙巯丁二酰亚胺，左乙拉西坦和拉考酰胺的化学片段。最初的抗惊厥筛选是在小鼠（ip）上使用“经典”最大电休克（MES）和皮下戊四氮（scPTZ）测试，以及药物耐受性边缘癫痫发作的六赫兹（6 Hz）模型。应用旋转脚架试验，确定了急性神经毒性。在小鼠中（跨越临床前惊厥模型活动的宽光谱的ip）显示的化合物4，5，11，和19。最有利的抗惊厥特性显示4（ED 50 MES = 96.9 mg / kg，ED 50 sc PTZ = 75.4 mg / kg，ED 50 6 Hz = 44.3 mg / kg）， 在旋转试验中显示TD

  DOI：

  10.1016/j.bmc.2016.04.066
• 作为产物：
  描述：

  甲基丁二酸 、 DL-丙氨酸 反应 1.0h， 以75%的产率得到2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanoic acid
  参考文献：
  名称：

  New hybrid molecules with anticonvulsant and antinociceptive activity derived from 3-methyl- or 3,3-dimethyl-1-[1-oxo-1-(4-phenylpiperazin-1-yl)propan-2-yl]pyrrolidine-2,5-diones

  摘要：

  The purpose of this study was to synthetize the focused library of 34 new piperazinamides of 3-methyland 3,3-dimethyl-(2,5-dioxopyrrolidin-1-yl) propanoic or butanoic acids as potential new hybrid anticonvulsants. These hybrid molecules join the chemical fragments of well-known antiepileptic drugs (AEDs) such as ethosuximide, levetiracetam, and lacosamide. Compounds 5-38 were prepared in a coupling reaction of the 3-methyl-or 3,3-dimethyl-2-(2,5-dioxopyrrolidin-1-yl) propanoic (1, 2) or butanoic acids (3, 4) with the appropriately substituted secondary amines in the presence of the N, N-carbonyldiimidazole reagent. The initial anticonvulsant screening was performed in mice (ip) using the 'classical' maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests as well as in the six-Hertz (6 Hz) model of pharmacoresistant limbic seizures. The acute neurological toxicity was determined applying the chimney test. The broad spectra of activity across the preclinical seizure models in mice ip displayed compounds 7, 15, and 36. The most favorable anticonvulsant properties demonstrated 15 (ED50 MES = 74.8 mg/kg, ED50 scPTZ = 51.6 mg/kg, ED50 6 Hz = 16.8 mg/kg) which showed TD50 = 213.3 mg/kg in the chimney test that yielded satisfying protective indexes (PI MES = 2.85, PI scPTZ = 4.13, PI 6 Hz = 12.70) at time point of 0.5 h. As a result, compound 15 displayed comparable or better safety profile than clinically relevant AEDs: ethosuximide, lacosamide or valproic acid. In the in vitro assays compound 15 was observed as relatively effective binder to the neuronal voltage-sensitive sodium and L-type calcium channels. Beyond the anticonvulsant properties, 6 compounds diminished the pain responses in the formalin model of tonic pain in mice. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.027

文献信息

• US7645771B2
  申请人：——

  公开号：US7645771B2

  公开（公告）日：2010-01-12
• New hybrid molecules with anticonvulsant and antinociceptive activity derived from 3-methyl- or 3,3-dimethyl-1-[1-oxo-1-(4-phenylpiperazin-1-yl)propan-2-yl]pyrrolidine-2,5-diones
  作者：Krzysztof Kamiński、Mirosław Zagaja、Anna Rapacz、Jarogniew J. Łuszczki、Marta Andres-Mach、Michał Abram、Jolanta Obniska

  DOI：10.1016/j.bmc.2015.12.027

  日期：2016.2

  The purpose of this study was to synthetize the focused library of 34 new piperazinamides of 3-methyland 3,3-dimethyl-(2,5-dioxopyrrolidin-1-yl) propanoic or butanoic acids as potential new hybrid anticonvulsants. These hybrid molecules join the chemical fragments of well-known antiepileptic drugs (AEDs) such as ethosuximide, levetiracetam, and lacosamide. Compounds 5-38 were prepared in a coupling reaction of the 3-methyl-or 3,3-dimethyl-2-(2,5-dioxopyrrolidin-1-yl) propanoic (1, 2) or butanoic acids (3, 4) with the appropriately substituted secondary amines in the presence of the N, N-carbonyldiimidazole reagent. The initial anticonvulsant screening was performed in mice (ip) using the 'classical' maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests as well as in the six-Hertz (6 Hz) model of pharmacoresistant limbic seizures. The acute neurological toxicity was determined applying the chimney test. The broad spectra of activity across the preclinical seizure models in mice ip displayed compounds 7, 15, and 36. The most favorable anticonvulsant properties demonstrated 15 (ED50 MES = 74.8 mg/kg, ED50 scPTZ = 51.6 mg/kg, ED50 6 Hz = 16.8 mg/kg) which showed TD50 = 213.3 mg/kg in the chimney test that yielded satisfying protective indexes (PI MES = 2.85, PI scPTZ = 4.13, PI 6 Hz = 12.70) at time point of 0.5 h. As a result, compound 15 displayed comparable or better safety profile than clinically relevant AEDs: ethosuximide, lacosamide or valproic acid. In the in vitro assays compound 15 was observed as relatively effective binder to the neuronal voltage-sensitive sodium and L-type calcium channels. Beyond the anticonvulsant properties, 6 compounds diminished the pain responses in the formalin model of tonic pain in mice. (c) 2015 Elsevier Ltd. All rights reserved.
• Design, synthesis and anticonvulsant activity of new hybrid compounds derived from N -phenyl-2-(2,5-dioxopyrrolidin-1-yl)-propanamides and -butanamides
  作者：Krzysztof Kamiński、Anna Rapacz、Barbara Filipek、Jolanta Obniska

  DOI：10.1016/j.bmc.2016.04.066

  日期：2016.7

  5-dioxopyrrolidin-1-yl)butanamide derivatives as potential new hybrid anticonvulsant agents was synthesized. These hybrid molecules were obtained as close analogs of previously described N-benzyl derivatives and fuse the chemical fragments of clinically relevant antiepileptic drugs such as ethosuximide, levetiracetam, and lacosamide. The initial anticonvulsant screening was performed in mice (ip) using the ‘classical’

  重点研究了21种新的N-苯基-2-（2,5-二氧杂吡咯烷-1-基）丙酰胺，2-（3-甲基-2,5-二氧杂吡咯烷-1-基）丙酰胺和2-（2，合成了5-二氧杂吡咯烷-1-基）丁酰胺衍生物作为潜在的新型杂化抗惊厥药。这些杂合分子是作为先前描述的N-苄基衍生物的紧密类似物获得的，并且融合了临床上相关的抗癫痫药如乙巯丁二酰亚胺，左乙拉西坦和拉考酰胺的化学片段。最初的抗惊厥筛选是在小鼠（ip）上使用“经典”最大电休克（MES）和皮下戊四氮（scPTZ）测试，以及药物耐受性边缘癫痫发作的六赫兹（6 Hz）模型。应用旋转脚架试验，确定了急性神经毒性。在小鼠中（跨越临床前惊厥模型活动的宽光谱的ip）显示的化合物4，5，11，和19。最有利的抗惊厥特性显示4（ED 50 MES = 96.9 mg / kg，ED 50 sc PTZ = 75.4 mg / kg，ED 50 6 Hz = 44.3 mg / kg）， 在旋转试验中显示TD