2-(S)-tert-butoxycarbonylaminopentanedioic acid 1-butyl ester

• 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-(S)-tert-butoxycarbonylaminopentanedioic acid 1-butyl ester
• 英文别名: (4S)-5-butoxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoic acid
• 化学式: C₁₄H₂₅NO₆
• 分子量: 303.356
• InChiKey: AZIHWKHQCYWLHP-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(S)-tert-butoxycarbonylaminopentanedioic acid 1-butyl ester 在 吡啶 、 盐酸 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 49.25h， 生成 4-{[2-(S)-(benzoylsulfanyl)ethyl]carbamoyl}-1-butoxy-1-oxobutan-2-aminium chloride
  参考文献：
  名称：

  Synthesis of diacylated γ-glutamyl-cysteamine prodrugs, and in vitro evaluation of their cytotoxicity and intracellular delivery of cysteamine

  摘要：

  To overcome the major disadvantages of cysteamine, the only registered treatment for the rare genetic disease cystinosis, nine prodrugs of gamma-glutamyl-cysteamine (4) were synthesized for evaluation. Esterification of the thiol conferred oxidative stability, while sufficient lipophilicity for oral bioavailability was achieved by acylation of the alpha-carboxyl group of gamma-glutamyl-cysteamine (4). Low cytotoxicity was observed in cultured HaCaT keratinocytes using the MIT assay, with EC50 values higher than or similar to that of cysteamine. Successful uptake of the esterified prodrugs and the subsequent release of cysteamine into cultured human proximal tubule epithelial cells were demonstrated using CMQT derivatisation and HPLC with UV detection. These prodrugs show potential as novel delivery vehicles of cysteamine to improve the treatment of the genetic disorder nephropathic cystinosis. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.027
• 作为产物：
  描述：

  2-(S)-tert-butoxycarbonylaminopentanedioic acid 5-benzyl ester 1-butyl ester 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 3.0 ℃ 、300.01 kPa 条件下， 反应 20.0h， 以89%的产率得到2-(S)-tert-butoxycarbonylaminopentanedioic acid 1-butyl ester
  参考文献：
  名称：

  Synthesis of diacylated γ-glutamyl-cysteamine prodrugs, and in vitro evaluation of their cytotoxicity and intracellular delivery of cysteamine

  摘要：

  To overcome the major disadvantages of cysteamine, the only registered treatment for the rare genetic disease cystinosis, nine prodrugs of gamma-glutamyl-cysteamine (4) were synthesized for evaluation. Esterification of the thiol conferred oxidative stability, while sufficient lipophilicity for oral bioavailability was achieved by acylation of the alpha-carboxyl group of gamma-glutamyl-cysteamine (4). Low cytotoxicity was observed in cultured HaCaT keratinocytes using the MIT assay, with EC50 values higher than or similar to that of cysteamine. Successful uptake of the esterified prodrugs and the subsequent release of cysteamine into cultured human proximal tubule epithelial cells were demonstrated using CMQT derivatisation and HPLC with UV detection. These prodrugs show potential as novel delivery vehicles of cysteamine to improve the treatment of the genetic disorder nephropathic cystinosis. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.027

文献信息

• C7-fluoro substituted tetracycline compounds
  申请人：Tetraphase Pharmaceuticals, Inc.

  公开号：EP2682387A2

  公开（公告）日：2014-01-08

  The present invention is directed to a compound falling under Structural Formula (A): or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.

  本发明涉及一种属于结构式（A）的化合物： 或其药学上可接受的盐。结构式（A）的变量在此定义。还描述了一种包含结构式（A）化合物的药物组合物及其治疗用途。
• C7-FLUORO SUBSTITUTED TETRACYCLINE COMPOUNDS
  申请人：Tetraphase Pharmaceuticals, Inc.

  公开号：EP3000805B1

  公开（公告）日：2017-10-18
• C7-Fluoro Substituted Tetracycline Compounds
  申请人：Zhou Jingye

  公开号：US20120302527A1

  公开（公告）日：2012-11-29

  The present invention is directed to a compound represented by Structural Formula (A): or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.
• US8501716B2
  申请人：——

  公开号：US8501716B2

  公开（公告）日：2013-08-06
• US8796245B2
  申请人：——

  公开号：US8796245B2

  公开（公告）日：2014-08-05