N-(1-(苯基乙酰基)-L-脯氨酰)甘氨酸乙酯 | 157115-85-0

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 甘氨酸类衍生物
• 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: N-(1-(苯基乙酰基)-L-脯氨酰)甘氨酸乙酯
• 中文别名: 苯乙酰甘氨酸乙酯；Noopept；GVS-111；甘氨酸乙酯
• 英文名称: N-phenylacetyl-L-prolylglycine ethyl ester
• 英文别名: noopept；ethyl 2-[[(2S)-1-(2-phenylacetyl)pyrrolidine-2-carbonyl]amino]acetate
• CAS: 157115-85-0
• 化学式: C₁₇H₂₂N₂O₄
• 分子量: 318.373
• InChiKey: PJNSMUBMSNAEEN-AWEZNQCLSA-N

物化性质

• 熔点：
  94.0 to 98.0 °C
• 沸点：
  547.3±50.0 °C(Predicted)
• 密度：
  1.202±0.06 g/cm3(Predicted)
• 溶解度：
  溶于DMSO（高达25mg/ml）

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2942000000
• RTECS号：
  MC0814400
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  -20°C

制备方法与用途

NOOPEPT简介

NOOPEPT的商品名是N-(1-(苯基乙酰基)-L-脯氨酰)甘氨酸乙酯，主要用于治疗肥胖、酒精依赖性退化或中毒性损伤等疾病。

生物活性

Omberacetam（GVS-111）是一种多肽膳食补充剂。体外研究表明，Nooglutil在竞争性结合选择性AMPA受体激动剂([G-3H]Ro 48-8587)的结合位点时表现出药理学显著性，其IC50值为6.4±0.2微摩尔，而Noopept对该结合位点的竞争性较低一个数量级（IC50 = 80±5.6微摩尔）[1]。GVS-111在过氧化氢处理后显著增加神经元存活率，并表现出剂量依赖性的神经保护活性，从10纳摩尔到100微摩尔均有作用，其半数有效浓度（IC50）值为1.21±0.07微摩尔。GVS-111还抑制了过氧化氢或硫酸亚铁处理后神经元内的自由基积累和脂质过氧化损伤，表明其具有抗氧化机制[2]。

体内研究

静脉注射N-苯基乙酰-L-脯氨酰甘氨酸乙酯（GVS-111）在梗死发生后1小时首次给药，并随后连续9个术后日每天给药一次，最后一次给药前15分钟进行测试。结果显示，该药物能减轻缺血性损伤后的功能缺陷[3]。体内研究还表明，即使在大剂量（5毫克/公斤）腹腔注射后1小时内，GVS-111也没有在大鼠脑中被检测到[4]。二肽在预防佐剂性关节炎模型中的抗炎效果最为显著，在25天的治疗期内，药物以0.5毫克/公斤（肌内注射）或5毫克/公斤（口服）的剂量给药，显著减少了慢性免疫炎症（第12天分别减少94.0%和74.1%）[5]。

反应信息

• 作为反应物：
  描述：

  N-(1-(苯基乙酰基)-L-脯氨酰)甘氨酸乙酯 在 氨 作用下， 以 甲醇 为溶剂， 以95%的产率得到N-phenylacetyl-L-prolylglycine amide
  参考文献：
  名称：

  Synthesis and antiamnesic activity of a series of N-acylprolyl-containing dipeptides

  摘要：

  Esters and amides of a series of N-acylprolyl-containing dipeptides were synthesized. It was established that these substances possess the ability to prevent memory decline evoked by maximal electroshock (MES) in a passive avoidance step-through paradigm. These N-acylprolyl-containing dipeptides were designed as analogues of pyroglutamyl-containing dipeptides, which we previously demonstrated to be highly active nootropics. Among the structure-activity relationships explored were the effect of N-acyl-substitution size, C-terminal substitution and the nature of the second amino acid. The optimal N-acyl moiety was the N-phenyl-acetyl group, while the optimal C-terminal substitution-esters were those derived from low alkyl alcohols. The optimal second amino acids were Asp, Glu or their fragments, Gly, beta-Ala, GABA. Compound 1 (N-phenylacetylprolylglycine ethyl ester) was selected for further evaluation in impaired cognitive functions. It was supposed that esters and unsubstituted amides of N-acylprolylglycines are prodrugs,which convert to the bioactive cyclo-(Pro-Gly) by virtue of enzymatic or chemical lability within the body.

  DOI：

  10.1016/0223-5234(96)80448-x
• 作为产物：
  描述：

  L-脯氨酸 在 N-甲基吗啉 、 sodium hydroxide 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.78h， 生成 N-(1-(苯基乙酰基)-L-脯氨酰)甘氨酸乙酯
  参考文献：
  名称：

  Synthesis and antiamnesic activity of a series of N-acylprolyl-containing dipeptides

  摘要：

  Esters and amides of a series of N-acylprolyl-containing dipeptides were synthesized. It was established that these substances possess the ability to prevent memory decline evoked by maximal electroshock (MES) in a passive avoidance step-through paradigm. These N-acylprolyl-containing dipeptides were designed as analogues of pyroglutamyl-containing dipeptides, which we previously demonstrated to be highly active nootropics. Among the structure-activity relationships explored were the effect of N-acyl-substitution size, C-terminal substitution and the nature of the second amino acid. The optimal N-acyl moiety was the N-phenyl-acetyl group, while the optimal C-terminal substitution-esters were those derived from low alkyl alcohols. The optimal second amino acids were Asp, Glu or their fragments, Gly, beta-Ala, GABA. Compound 1 (N-phenylacetylprolylglycine ethyl ester) was selected for further evaluation in impaired cognitive functions. It was supposed that esters and unsubstituted amides of N-acylprolylglycines are prodrugs,which convert to the bioactive cyclo-(Pro-Gly) by virtue of enzymatic or chemical lability within the body.

  DOI：

  10.1016/0223-5234(96)80448-x

文献信息

• [EN] ARYL IMIDAZOLE COMPOUNDS AND THEIR USE AS BETA AMYLOID PRODUCTION INHIBITORS<br/>[FR] COMPOSÉ ARYLIMIDAZOLE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE PRODUCTION DE LA PROTÉINE AMYLOÏDE BÊTA
  申请人：EISAI R&D MAN CO LTD

  公开号：WO2010098488A1

  公开（公告）日：2010-09-02

  A compound represented by the formula (I): or a pharmacologically acceptable salt or ester thereof, wherein Ring A represents a triazolyl group or the like which may be substituted, Ring B represents a phenyl group or the like which may be substituted, X1 represents a single bond or the like, R1 and R2 each represent a C1-6 alkyl group or the like, m represents an integer of 0 to 3, and n represents an integer of 0 to 2, is effective as a therapeutic agent for a disease caused by Aβ.

  一种由化学式(I)表示的化合物，或其药理学上可接受的盐或酯，其中环A代表可能被取代的三唑基团或类似物，环B代表可能被取代的苯基团或类似物，X1代表单键或类似物，R1和R2分别代表C1-6烷基或类似物，m代表0到3的整数，n代表0到2的整数，对于由Aβ引起的疾病具有治疗作用。
• MULTI-CYCLIC COMPOUNDS
  申请人：KIMURA Teiji

  公开号：US20090062529A1

  公开（公告）日：2009-03-05

  A compound represented by the formula (I): or a pharmacologically acceptable salt thereof, wherein Ar 1 represents an imidazolyl group or the like which may be substituted with a C1-6 alkyl group, Ar 2 represents a phenyl group or the like which may be substituted with a C1-6 alkoxy group, X 1 represents a double bond or the like and Het represents a triazolyl group or the like which may be substituted with a C1-6 alkyl group or the like, is effective as a therapeutic or prophylactic agent for a disease caused by Aβ.

  一种由化学式(I)表示的化合物或其药理学可接受的盐，其中Ar1代表可用C1-6烷基基团取代的咪唑基团或类似基团，Ar2代表可用C1-6烷氧基团取代的苯基团或类似基团，X1代表双键或类似基团，Het代表可用C1-6烷基基团或类似基团取代的三唑基团或类似基团，对由Aβ引起的疾病具有治疗或预防作用。
• [EN] NITROGEN-CONTAINING FUSED HETEROCYCLIC COMPOUNDS AND THEIR USE AS BETA AMYLOID PRODUCTION INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES CONDENSÉS CONTENANT DE L'AZOTE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE PRODUCTION DE LA BÊTA-AMYLOÏDE
  申请人：EISAI R&D MAN CO LTD

  公开号：WO2010098487A1

  公开（公告）日：2010-09-02

  A compound represented by the formula [I]: or a pharmacologically acceptable salt or ester thereof, wherein Ring A represents a five-membered aromatic heterocyclic group or the like fused with a non-aromatic ring group, which may be substituted, Ring B represents a phenyl group or the like which may be substituted, X1 represents a single bond or the like, R1 and R2 each represent a C1-6 alkyl group or the like, m represents an integer of 0 to 3, and n represents an integer of 0 to 2, is effective as a therapeutic agent for a disease caused by Aβ.

  化合物的分子式为[I]：或其药理学可接受的盐或酯，其中环A代表一个五元芳香杂环基团或类似于非芳香环基团的融合物，可以被取代，环B代表一个苯基或类似的基团，可以被取代，X1代表一个单键或类似物，R1和R2分别代表一个C1-6烷基基团或类似物，m表示0到3的整数，n表示0到2的整数，对由Aβ引起的疾病具有治疗作用。
• [EN] IMIDAZOLYLPYRAZINE DERIVATIVES<br/>[FR] DÉRIVÉS D'IMIDAZOLYLPYRAZINE
  申请人：EISAI R&D MAN CO LTD

  公开号：WO2010098495A1

  公开（公告）日：2010-09-02

  To provide a novel low-molecular-weight compound that inhibits the production of amyloid-β (Aβ ). A compound represented by the formula [I]: or a pharmacologically acceptable salt or ester thereof, wherein R1 and R2 are the same or different and each represent a substituent selected from the following Substituent Group a1; m represents an integer of 0 to 3; n represents an integer of 0 to 2; X1 represents a single bond or the like; X2 represents a single bond or the like; Ring A represents a five-membered aromatic heterocyclic group or the like which contains two or more nitrogen atoms and may have 1 to 3 substituents selected from the following Substituent Group b1; and Ring B represents a monocyclic or fused cyclic aromatic ring group such as the formula [2] which may have 1 to 3 substituents selected from the following Substituent Group c1, is effective as a therapeutic agent for a disease such as Alzheimer's disease. Substituent Group a1: a C1-6 alkyl group and the like Substituent Group b1: a C1-6 alkyl group and the like Substituent Group c1: an amino group and the like

  提供一种新型低分子量化合物，该化合物能够抑制淀粉样蛋白-β（Aβ）的产生。表示为化学式[I]的化合物，或其药理学上可接受的盐或酯，其中R1和R2相同或不同，每个代表以下取代基团a1中选择的取代基；m代表0到3的整数；n代表0到2的整数；X1代表单键或类似物；X2代表单键或类似物；环A代表含有两个或更多氮原子并且可能具有1到3个取代基团b1中选择的取代基的五元芳香杂环基团或类似物；环B代表可能具有1到3个取代基团c1中选择的取代基的单环或融合环芳香环基团，如化学式[2]所示，对于阿尔茨海默病等疾病具有治疗作用。取代基团a1：C1-6烷基基团等；取代基团b1：C1-6烷基基团等；取代基团c1：氨基团等。
• Nitrogen-Containing Fused Heterocyclic Compounds and Their use as Beta Amyloid Production Inhibitors
  申请人：Kitazawa Noritaka

  公开号：US20120053171A1

  公开（公告）日：2012-03-01

  A compound represented by the formula [I]: or a pharmacologically acceptable salt or ester thereof, wherein Ring A represents a five-membered aromatic heterocyclic group or the like fused with a non-aromatic ring group, which may be substituted, Ring B represents a phenyl group or the like which may be substituted, X1 represents a single bond or the like, R1 and R2 each represent a C1-6 alkyl group or the like, m represents an integer of 0 to 3, and n represents an integer of 0 to 2, is effective as a therapeutic agent for a disease caused by Aβ.

  化合物的化学式为[I]，或其药理学上可接受的盐或酯，其中环A代表一个五元芳香杂环基团或类似物，与非芳香环基团融合，可以被取代，环B代表苯基或类似物，可以被取代，X1代表单键或类似物，R1和R2各代表C1-6烷基或类似物，m代表0至3的整数，n代表0至2的整数，该化合物对由Aβ引起的疾病具有治疗作用。