N-benzyloxycarbonyl-glycyl-L-2-methylproline | 869001-86-5

• 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: N-benzyloxycarbonyl-glycyl-L-2-methylproline
• 英文别名: L-Proline, N-[(phenylmethoxy)carbonyl]glycyl-2-methyl-；(2S)-2-methyl-1-[2-(phenylmethoxycarbonylamino)acetyl]pyrrolidine-2-carboxylic acid
• CAS: 869001-86-5
• 化学式: C₁₆H₂₀N₂O₅
• 分子量: 320.345
• InChiKey: YBKNTPKTWJAXOY-INIZCTEOSA-N

物化性质

• 沸点：
  569.2±50.0 °C(Predicted)
• 密度：
  1.293±0.06 g/cm3(Predicted)
• LogP：
  1.521

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  N-benzyloxycarbonyl-glycyl-L-2-methylproline 在 碘苯二乙酸 、 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以47%的产率得到
  参考文献：
  名称：

  通过二肽衍生物的脱羧环化合成多环氨基杂环

  摘要：

  报道了二肽衍生物的氧化脱羧分子内环化。苯碘( III )二乙酸酯(PIDA)与BF 3 ·OEt 2的组合促进了这种转化。该反应提供了获得各种有价值的多环 N-杂环支架的途径，这些支架包含 5-、6-或 7-元环。

  DOI：

  10.1039/d2cc00167e
• 作为产物：
  描述：

  (2R,5S)-2-trichloromethyl-1-aza-3-oxabicyclo[3.3.0]octan-4-one 在 sodium hydroxide 、 正丁基锂 、 氯化亚砜 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙胺 、 二异丙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 45.33h， 生成 N-benzyloxycarbonyl-glycyl-L-2-methylproline
  参考文献：
  名称：

  Synthesis of proline-modified analogues of the neuroprotective agent glycyl-l-prolyl-glutamic acid (GPE)

  摘要：

  The synthesis of ten proline-modified analogues of the neuroprotective tripeptide GPE is described. Five of the analogues incorporate a proline residue with a hydrophobic group at C-2 and two further analogues have this side chain locked into a spirolactam ring system. The pyrrolidine ring was also modified by replacing the gamma-CH2 group with sulfur and/or incorporation of two methyl groups at C-5. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.08.026

文献信息

• [EN] TREATMENT OF AUTISM SPECTRUM DISORDERES USING GLYCYL-L-2-METHYLPROLYL-L-GLUTAMIC ACID<br/>[FR] TRAITEMENT DE TROUBLES DU SPECTRE AUTISTIQUE EN UTILISANT L'ACIDE GLYCYL-L-2-MÉTHYLPROLYL-L-GLUTAMIQUE
  申请人：NEUREN PHARMACEUTICALS LTD

  公开号：WO2012102832A1

  公开（公告）日：2012-08-02

  This invention provides compounds, compositions and methods for treating Autism Spectrum Disorders (ASD) using glycyl-2-methylprolyl-glutamic acid (G-2-MePE) and analogs thereof. Autism Spectrum Disorders include Autism, Autistic Disorder, Asperger Syndrome, Childhood Disintegrative Disorder, Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS), Fragile X Syndrome, and Rett Syndrome. Compositions containing compounds include water-soluble formulations, water-in-oil micro-emulsions, water-in-oil coarse emulsions, water-in-oil liquid crystals, nanocapsules, tablets, and orally administered gels. The compounds and compositions of this invention can be administered intravenously, intraventricularly, parenterally, or orally, and can be effective in treating neurodegeneration, promoting neurological function, treating seizure activity and other symptoms of ASD, and can prolong life in animals including human beings having Autism Spectrum Disorders.

  该发明提供了使用甘氨基-2-甲基脯氨酰-谷氨酸 (G-2-MePE) 及其类似物治疗自闭症谱系障碍（ASD）的化合物、组合物和方法。自闭症谱系障碍包括自闭症、孤独症、亚斯伯格综合征、童年解体性障碍、广泛性发育障碍-未特定（PDD-NOS）、脆性X综合征和雷特综合征。含有化合物的组合物包括水溶性配方、水-油微乳液、水-油粗乳液、水-油液晶、纳米胶囊、片剂和口服凝胶。该发明的化合物和组合物可以通过静脉内、脑室内、肠外或口服途径给药，可有效治疗神经退行性疾病，促进神经功能，治疗癫痫活动和其他ASD症状，并可延长患有自闭症谱系障碍的动物（包括人类）的寿命。
• [EN] TREATMENT OF AUTISM SPECTRUM DISORDERS USING GLYCYL-L-2-METHYLPROLYL-L-GLUTAMIC ACID<br/>[FR] TRAITEMENT DE TROUBLES DU SPECTRE AUTISTIQUE À L'AIDE DE L'ACIDE GLYCYL-L-2-MÉTHYLPROLYL-L-GLUTAMIQUE
  申请人：NEUREN PHARMACEUTICALS LTD

  公开号：WO2014085480A1

  公开（公告）日：2014-06-05

  This invention provides compounds, compositions and methods for treating Autism Spectrum Disorders (ASD) using glycyl-2-methyIprolyl-glutamic acid (G-2-MePE) and analogs thereof. Autism Spectrum Disorders include Autism, Autistic Disorder, Asperger Syndrome, Childhood Disintegrative Disorder, Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS), Fragile X Syndrome, and Rett Syndrome. Compositions containing compounds include water-soluble formulations, water-in-oil micro-emulsions, water-in-oil coarse emulsions, water-in-oil liquid crystals, nanocapsules, tablets, and orally administered gels. The compounds and compositions of this invention can be administered intravenously, intraventricularly, parenterally, or orally, and can be effective in treating neurodegeneration, promoting neurological function, treating seizure activity and other symptoms of ASD, and can prolong life in animals including human beings having Autism Spectrum Disorders.

  这项发明提供了使用甘氨酰-2-甲基脯氨酰-谷氨酸酸（G-2-MePE）及其类似物治疗自闭症谱系障碍（ASD）的化合物、组合物和方法。自闭症谱系障碍包括自闭症、孤独症障碍、亚斯伯格综合症、儿童解体性障碍、广泛发育障碍-未明确其他类型（PDD-NOS）、脆性X综合症和雷特综合症。含有这些化合物的组合物包括水溶性配方、水-油微乳液、水-油粗乳液、水-油液晶体、纳米胶囊、片剂和口服凝胶。这项发明的化合物和组合物可以通过静脉内、脑室内、肠外或口服给药，并且可以有效治疗神经退行性疾病、促进神经功能、治疗癫痫活动和其他自闭症谱系障碍症状，并且可以延长患有自闭症谱系障碍的动物（包括人类）的寿命。
• Synthesis of isotopically labelled glycyl-L-prolyl-L-glutamic acid (Glypromate®) and derivatives
  作者：Paul W. R. Harris、Margaret A. Brimble

  DOI：10.1002/jlcr.1075

  日期：2006.5

  The related tripeptides glycyl-L-prolyl-L-glutamic acid (GPE) and glycyl-L-2-methylprolyl-L-glutamic acid (G-2-MePE) were labelled with commercially available [1,2,3,4,5-13C5, 2-15N1]-L-glutamic acid in 3 steps in excellent overall yield with high isotope incorporation. A related cyclic dipeptide was labelled with [2,2-2H2, 2-15N1]glycine giving a mixture of compounds resulting from deuterium scrambling

  相关的三肽甘氨酰-L-脯氨酰-L-谷氨酸 (GPE) 和甘氨酰-L-2-甲基脯氨酰-L-谷氨酸 (G-2-MePE) 用市售 [1,2,3,4, 5-13C5, 2-15N1]-L-谷氨酸分 3 个步骤以优异的总收率和高同位素掺入量获得。相关的环状二肽用 [2,2-2H2, 2-15N1] 甘氨酸标记，得到由氘扰乱产生的化合物混合物。版权所有 © 2006 John Wiley & Sons, Ltd.
• Effects of glycyl-2 methyl prolyl glutamate on neurodegeneration
  申请人：Gluckman David Peter

  公开号：US20070298009A1

  公开（公告）日：2007-12-27

  This invention provides analogs and peptidomimetics of glycyl-L-prolyl-L-glutamic acid (GPE). In particular, this invention relates to GPE analogs and peptidomimetics that are anti-apoptotic, anti-necrotic and have neuroprotective effects. These agents are useful in treating neurodegeneration and behavioural disorders caused by toxins, traumatic brain injury and autoimmune disorders of the brain, such as multiple sclerosis and in reducing seizures.

  该发明提供了甘氨酰-L-脯氨酰-L-谷氨酸（GPE）的类似物和肽类类似物。特别是，该发明涉及具有抗凋亡、抗坏死和神经保护作用的GPE类似物和肽类类似物。这些药物对治疗由毒素、创伤性脑损伤和脑自身免疫性疾病（如多发性硬化症）引起的神经退行性和行为障碍以及减少癫痫发作具有用处。
• COGNITIVE ENHANCEMENT AND COGNITIVE THERAPY USING GLYCYL-L-2-METHYLPROLYL-L-GLUTAMIC ACID
  申请人：Gluckman Peter David

  公开号：US20110112033A1

  公开（公告）日：2011-05-12

  This invention provides compounds, compositions and methods for treating a cognitive disorder or memory disorder in animals that result from aging or other neurodegenerative condition. In particular, compounds of this invention can stimulate neural cell growth, increased amounts of cells containing a key enzyme needed for production of the cholinergic neurotransmitter, and can improve memory and cognitive function in animals who have experienced a loss of memory or cognitive function.

  本发明提供了用于治疗动物中由于衰老或其他神经退行性疾病导致的认知障碍或记忆障碍的化合物、组合物和方法。特别地，本发明的化合物可以刺激神经细胞的生长，增加含有乙酰胆碱神经递质生产所需的关键酶的细胞数量，并可以改善失去记忆或认知功能的动物的记忆和认知功能。