tert-butyl 2-{[2-({N2-(4-{[(2-amino-4-hydroxypteridin-6-yl)methyl]amino}benzoyl)-N1-[2-({2-[(tert-butoxycarbonyl)amino]ethyl}dithio)ethyl]-α-glutaminyl}amino)ethyl]dithio}ethylcarbamate | 1301165-94-5

• 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: tert-butyl 2-{[2-({N2-(4-{[(2-amino-4-hydroxypteridin-6-yl)methyl]amino}benzoyl)-N1-[2-({2-[(tert-butoxycarbonyl)amino]ethyl}dithio)ethyl]-α-glutaminyl}amino)ethyl]dithio}ethylcarbamate
• CAS: 1301165-94-5
• 化学式: C₃₇H₅₅N₁₁O₈S₄
• 分子量: 910.177
• InChiKey: HVLZPBZKBWGIEX-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.24
• 重原子数：
  60.0
• 可旋转键数：
  23.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  273.8
• 氢给体数：
  8.0
• 氢受体数：
  18.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-{[2-({N2-(4-{[(2-amino-4-hydroxypteridin-6-yl)methyl]amino}benzoyl)-N1-[2-({2-[(tert-butoxycarbonyl)amino]ethyl}dithio)ethyl]-α-glutaminyl}amino)ethyl]dithio}ethylcarbamate 在 盐酸 、 水 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以95%的产率得到2-({2-[(N2-(4-{[(2-amino-4-hydroxypteridin-6-yl)methyl]amino}benzoyl)-N1-{2-[(2-ammonioethyl)dithio]ethyl}-α-glutaminyl)amino]ethyl}dithio)ethanammoniumdichloride
  参考文献：
  名称：

  Folate pro-drug of cystamine as an enhanced treatment for nephropathic cystinosis

  摘要：

  Nephropathic cystinosis is a rare autosomal recessive disease characterised by raised intracellular levels of the amino acid, cystine. If untreated, the disease, progressively deteriorates towards end stage renal disease (ESRD) at the end of the first decade. The disease is caused by a defect in the lysosomal transport mechanism for cystine. The treatment of choice is the aminothiol cysteamine which acts as a lysine mimic. However, cysteamine possesses an offensive taste and smell and irritates the gastrointestinal tract leading to nausea and vomiting following administration. Furthermore, the rapid metabolism of cysteamine requires oral administration every 6 h for life, in consequence, the patient compliance is poor. As part of our continuing work to obtain new pro-drugs for the treatment of this genetic disease, we have synthesised a folate derivative of cystamine, the disulfide derivative of cysteamine. This new pro-drug was non cytotoxic, showed greater ability to deplete intralysosomal cystine than the current treatment, and, in fact has been the most effective reducer of intralysosomal cystine discovered in our laboratories to date. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.048
• 作为产物：
  描述：

  folate 、 T-BOC-胱胺 在 吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 水 为溶剂， 以96%的产率得到tert-butyl 2-{[2-({N2-(4-{[(2-amino-4-hydroxypteridin-6-yl)methyl]amino}benzoyl)-N1-[2-({2-[(tert-butoxycarbonyl)amino]ethyl}dithio)ethyl]-α-glutaminyl}amino)ethyl]dithio}ethylcarbamate
  参考文献：
  名称：

  Folate pro-drug of cystamine as an enhanced treatment for nephropathic cystinosis

  摘要：

  Nephropathic cystinosis is a rare autosomal recessive disease characterised by raised intracellular levels of the amino acid, cystine. If untreated, the disease, progressively deteriorates towards end stage renal disease (ESRD) at the end of the first decade. The disease is caused by a defect in the lysosomal transport mechanism for cystine. The treatment of choice is the aminothiol cysteamine which acts as a lysine mimic. However, cysteamine possesses an offensive taste and smell and irritates the gastrointestinal tract leading to nausea and vomiting following administration. Furthermore, the rapid metabolism of cysteamine requires oral administration every 6 h for life, in consequence, the patient compliance is poor. As part of our continuing work to obtain new pro-drugs for the treatment of this genetic disease, we have synthesised a folate derivative of cystamine, the disulfide derivative of cysteamine. This new pro-drug was non cytotoxic, showed greater ability to deplete intralysosomal cystine than the current treatment, and, in fact has been the most effective reducer of intralysosomal cystine discovered in our laboratories to date. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.048