3-(gamma-L-Glutamyl)-2(R,S)-Methylthiazolidine-4(R)-Carboxylic Acid | 190063-00-4

• 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
• 英文名称: 3-(gamma-L-Glutamyl)-2(R,S)-Methylthiazolidine-4(R)-Carboxylic Acid
• 英文别名: (4R)-3-[(4S)-4-amino-4-carboxybutanoyl]-2-methyl-1,3-thiazolidine-4-carboxylic acid
• CAS: 190063-00-4
• 化学式: C₁₀H₁₆N₂O₅S
• 分子量: 276.313
• InChiKey: ZBPZKAZHMOLGEN-BYRXKDITSA-N

物化性质

• 沸点：
  601.9±55.0 °C(Predicted)
• 密度：
  1.447±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  146
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(gamma-L-Glutamyl)-2(R,S)-Methylthiazolidine-4(R)-Carboxylic Acid 在 硫化氢 、 mercury(II) diacetate 作用下， 生成 5-L-谷氨酰-L-半胱氨酸
  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
• 作为产物：
  描述：

  2-甲基-1,3-噻唑烷-4-羧酸 在 N,O-双(三甲基硅烷基)三氟乙酰胺 、 一水合肼 、 三乙胺 作用下， 以 甲醇 、 水 为溶剂， 反应 0.83h， 生成 3-(gamma-L-Glutamyl)-2(R,S)-Methylthiazolidine-4(R)-Carboxylic Acid
  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

• Compounds that enhance the concentration of glutathione in tissues
  申请人：Regents of the University of Minnesota

  公开号：US05624955A1

  公开（公告）日：1997-04-29

  A pharmaceutical unit dosage form comprising an amount of a compound of the formula: ##STR1## is provided wherein R.sup.1 is a (C.sub.1 -C.sub.20)alkyl group, a (C.sub.6 -C.sub.12)aryl group, or a C.sub.3 -C.sub.18)cycloalkyl group and R.sup.2 is H or a (C.sub.1 -C.sub.19)alkyl group, a (C.sub.6 -C.sub.12)aryl group, a (C.sub.7 -C.sub.13)arylalkoxy group, a (C.sub.1 -C.sub.6)alkyoxy group, a (C.sub.3 -C.sub.18)cycloalkyl group, a ##STR2## group, or a --CH(R.sup.3)NH.sub.2 group wherein R.sup.3 is a side chain of a natural amino acid, and the pharmaceutically acceptable salts thereof; in combination with a pharmaceutically acceptable carrier, wherein said amount is effective to increase the concentration of glutathione in tissue.

  提供了一种药物单剂量形式，其中包含一定量的化合物，其化学式为：##STR1## 其中R.sup.1是（C.sub.1-C.sub.20）烷基，（C.sub.6-C.sub.12）芳基或C.sub.3-C.sub.18）环烷基，R.sup.2为H或（C.sub.1-C.sub.19）烷基，（C.sub.6-C.sub.12）芳基，（C.sub.7-C.sub.13）芳基烷氧基，（C.sub.1-C.sub.6）烷氧基，（C.sub.3-C.sub.18）环烷基，##STR2##基团或--CH（R.sup.3）NH.sub.2基团，其中R.sup.3是天然氨基酸的侧链，以及其药学上可接受的盐；与药学上可接受的载体结合，其中所述的量有效地增加组织中谷胱甘肽的浓度。
• Augmentation of Human and Rat Lenticular Glutathione in Vitro by Prodrugs of γ-<scp>l</scp>-Glutamyl-<scp>l</scp>-cysteine
  作者：Herbert T. Nagasawa、Jonathan F. Cohen、Ann M. Holleschau、William B. Rathbun

  DOI：10.1021/jm950674y

  日期：1996.1.1

  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.