(2S)-2-氨基-5-[[(2R)-1-乙氧基-1-氧代-3-巯基丙-2-基]氨基]-5-氧代戊酸 | 114627-30-4

• 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: (2S)-2-氨基-5-[[(2R)-1-乙氧基-1-氧代-3-巯基丙-2-基]氨基]-5-氧代戊酸
• 中文别名: N-γ-谷氨酰半胱氨酸乙基酯
• 英文名称: L-γ-glutamyl-L-cysteinylethyl ester
• 英文别名: γ-glutamylcisteinylethyl ester；γ-glutamylcysteine ethyl ester；γ-glutamylcysteinylethyl ester；TEI-2306；γ-L-glutamyl L-cysteine ethyl ester；N-gamma-Glutamylcysteine ethyl ester；(2S)-2-amino-5-[[(2R)-1-ethoxy-1-oxo-3-sulfanylpropan-2-yl]amino]-5-oxopentanoic acid
• CAS: 114627-30-4
• 化学式: C₁₀H₁₈N₂O₅S
• 分子量: 278.329
• InChiKey: IVEKVTHFAJJKGA-BQBZGAKWSA-N

物化性质

• 沸点：
  519.8±50.0 °C(Predicted)
• 密度：
  1.287±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.1
• 重原子数：
  18
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  120
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S)-2-氨基-5-[[(2R)-1-乙氧基-1-氧代-3-巯基丙-2-基]氨基]-5-氧代戊酸 生成 (2S)-2-amino-5-[[(2S)-3-[[(2R)-2-[[(4S)-4-amino-4-carboxybutanoyl]amino]-3-ethoxy-3-oxopropyl]disulfanyl]-1-ethoxy-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
  参考文献：
  名称：

  KITAHARA, SHIGEHISA;OHTSU, AKIRA;FUJII, KATSUHIKO

  摘要：

  DOI：
• 作为产物：
  描述：

  L-半胱氨酸乙酯 在 硫化氢 、 mercury(II) diacetate 、 一水合肼 、 三乙胺 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 4.08h， 生成 (2S)-2-氨基-5-[[(2R)-1-乙氧基-1-氧代-3-巯基丙-2-基]氨基]-5-氧代戊酸
  参考文献：
  名称：

  Augmentation of Human and Rat Lenticular Glutathione in Vitro by Prodrugs of γ-l-Glutamyl-l-cysteine

  摘要：

  A marked age-related decrease in glutathione (GSH) levels as well as depression of gamma-glutamylcysteine synthetase activity are factors that are believed to render the aged lens more susceptible to oxidative stress and, therefore, to cataractogenesis. Providing gamma-L-glutamyl-L-cysteine, the dipeptide precursor of GSH, would effectively bypass the compromised first step in its biosynthesis and should protect the lens from GSH depletion. Accordingly, some bioreversible sulfhydryl-, amino-, and C-terminal carboxyl-protected prodrug forms of this dipeptide were prepared. Sulfhydryl protection was in the form of an acetyl thioester, while the carboxyl group was protected as the ethyl ester. These prodrugs were evaluated for their GSH-enhancing activity in cultured human and rat lenses in vitro using an assay that measured the incorporation of [C-14]glycine into lens GSH. Ethyl S-acetyl-gamma-L-glutamyl-L-cysteinate (2) raised GSH levels in human lenses by 25% and in rat lenses by >150%. These data suggest that 2 may have potential as an anticataract agent since ethyl gamma-L-glutamyl-L-cysteinate (1a), the des-S-acetyl analog of 2, had been shown (by others) to protect against experimental rodent cataracts. GSH augmentation by 1a was 2% in human lenses and 25% in rat lenses, considerably less than that shown by 2.

  DOI：

  10.1021/jm950674y

文献信息

• [EN] METHODS FOR THE TREATMENT OF CYSTEAMINE SENSITIVE DISORDERS<br/>[FR] MÉTHODES DE TRAITEMENT DES TROUBLES SENSIBLES À LA CYSTÉAMINE
  申请人：THIOGENESIS THERAPEUTICS INC

  公开号：WO2019060634A1

  公开（公告）日：2019-03-28

  The invention features methods for the treatment of cystinosis and other cysteamine sensitive disorders in a subject including administration of a disulfide convertible to cysteamine in vivo. The methods can include the separate administration of a reducing agent to the subject to increase the bioavailablity and extend the plasma pharmacokinetic profile of the cysteamine produced following administration of the disulfide. The methods permit sustained cysteamine plasma concentrations in a subject.

  这项发明涉及治疗囊性氨基酸病和其他对半胱氨酸敏感的疾病的方法，包括在体内给予可转化为半胱氨酸的二硫化物。该方法可以包括向受试者单独给予还原剂，以增加半胱氨酸在给予二硫化物后产生的生物利用度，并延长血浆药代动力学特性。该方法允许受试者体内维持持续的半胱氨酸血浆浓度。
• NEW SQUALAMINE SOLID FORMS AND METHODS OF MAKING THE SAME
  申请人：Enterin, Inc.

  公开号：US20190127416A1

  公开（公告）日：2019-05-02

  Provided herein are crystalline solid forms of squalamine phosphate designated as Form 1 and Form 2, compositions containing one or both forms, and methods of their preparation and of their use.

  本文提供了作为Form 1和Form 2指定的鲨烷磷酸盐的结晶固态形式，包含一种或两种形式的组合物，以及它们的制备方法和使用方法。
• Tricyclic Lactam Derivatives as 11-Beta Hydroxysteroid Dehydrogenase Inhibitors
  申请人：Jaraskova Libuse

  公开号：US20080214597A1

  公开（公告）日：2008-09-04

  the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein X represents C or N; Y represents C or N; L represents a methyl or a direct bond; Z 1 represents a direct bond, C 1-2 alkyl- or a divalent radical of formula —CH 2 —CH═ (a) or —CH═ (b); Z 2 represents a direct bond, C 1-2 alkyl- or a divalent radical of formula —CH 2 —CH═ (a) or —CH═ (b); R 1 represents hydrogen, halo, cyano, amino, phenyl, hydroxy, C 1-4 alkyloxycarbonyl, hydroxycarbonyl, NR 3 R 4 or C 1-4 alkyl optionally substituted with one or more substituents selected from hydroxycarbonyl, phenyl, C 1-4 alkyloxy or NR 5 R 6 or R 1 represents C 1-4 alkyloxy- optionally substituted with one or more substituents selected from hydroxycarbonyl, phenyl, C 1-4 alkyloxy or NR 7 R 8 ; R 2 represents hydrogen, halo, C 1-4 alkyl or C 1-4 alkyloxy-; R 3 and R 4 each independently represent hydrogen, C 1-4 alkyl or C 1-4 alkylcarbonyl-; R 5 and R 6 each independently represent hydrogen, C 1-4 alkyl or C 1-4 alkylcarbonyl-; R 7 and R 8 each independently represent hydrogen, C 1-4 alkyl or C 1-4 alkylcarbonyl-; A represents phenyl or a monocyclic heterocycle selected from the group consisting of thiophenyl, furanyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, pyrridinyl, pyridazinyl, pyrimidinyl and piperazinyl.

  N-氧化物形式，其药学上可以接受的加成盐和立体化学异构体形式，其中X代表C或N；Y代表C或N；L代表甲基或直接键；Z1代表直接键，C1-2烷基或公式—CH2—CH═（a）或—CH═（b）的二价基团；Z2代表直接键，C1-2烷基或公式—CH2—CH═（a）或—CH═（b）的二价基团；R1代表氢，卤素，氰基，氨基，苯基，羟基，C1-4烷氧羰基，羟羰基，NR3R4或C1-4烷基，可选地被选自羟羰基，苯基，C1-4烷氧基或NR5R6的一个或多个取代基取代，或R1代表C1-4烷氧基，可选地被选自羟羰基，苯基，C1-4烷氧基或NR7R8的一个或多个取代基取代；R2代表氢，卤素，C1-4烷基或C1-4烷氧基；R3和R4各自独立地代表氢，C1-4烷基或C1-4烷基羰基；R5和R6各自独立地代表氢，C1-4烷基或C1-4烷基羰基；R7和R8各自独立地代表氢，C1-4烷基或C1-4烷基羰基；A代表苯基或从噻吩基，呋喃基，噁唑基，噻唑基，咪唑基，异噁唑基，异噻唑基，吡啶基，吡嗪基，嘧啶基和哌嗪基中选择的单环杂环。
• FORMULATIONS COMPRISING AMINOSTEROLS
  申请人：ZASLOFF Michael

  公开号：US20110123624A1

  公开（公告）日：2011-05-26

  This invention relates to stable aminosterol phosphate compositions. The aminosterol phosphate compositions permit administration without associated tissue damage and achieve a sustained release effect.

  本发明涉及稳定的氨基固醇磷酸盐组合物。这些氨基固醇磷酸盐组合物可在不造成组织损伤的情况下进行给药，并实现持续释放效果。
• METHODS OF TREATMENT USING AN AMINOSTEROL COMPOSITION
  申请人：Zasloff Michael

  公开号：US20140099281A1

  公开（公告）日：2014-04-10

  This invention relates to stable aminosterol phosphate compositions. The aminosterol phosphate compositions permit administration without associated tissue damage and achieve a sustained release effect.

  本发明涉及稳定的氨基固醇磷酸盐组合物。该氨基固醇磷酸盐组合物可以在不造成组织损伤的情况下进行给药，并实现持续释放效果。