Thioacetic acid S-((S)-2-tert-butoxycarbonylamino-3-tert-butylsulfanyl-propyl) ester | 139429-06-4

• 分子结构分类: 有机化合物
• 英文名称: Thioacetic acid S-((S)-2-tert-butoxycarbonylamino-3-tert-butylsulfanyl-propyl) ester
• CAS: 139429-06-4
• 化学式: C₁₄H₂₇NO₃S₂
• 分子量: 321.505
• InChiKey: IMRNSUWAEQUPOU-LLVKDONJSA-N

反应信息

• 作为反应物：
  描述：

  Thioacetic acid S-((S)-2-tert-butoxycarbonylamino-3-tert-butylsulfanyl-propyl) ester 在 sodium hydroxide 、 碘 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 [(S)-1-((S)-2-tert-Butoxycarbonylamino-3-tert-butylsulfanyl-propyldisulfanylmethyl)-2-tert-butylsulfanyl-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Potent and systemically active aminopeptidase N inhibitors designed from active-site investigation

  摘要：

  Derivatives of amino acids bearing various zinc-coordinating moieties (SH, COOH, CONHOH, and PO3H2) were synthesized and tested for their ability to inhibit aminopeptidase N (APN). Among them, beta-amino thiols were found to be the most efficient with IC50's in the 11-50 nM range. These results suggest that the S1 subsite of APN is a deep but not very large hydrophobic pocket, optimally fitting side chains of moderate bulk endowed with some degree of freedom. The iv administration of the inhibitors, alone, did not induce antinociceptive responses on the hot plate test in mice. However, in presence of 10 mg/kg acetorphan, a prodrug of the neutral endopeptidase inhibitor thiorphan, these compounds gave a large increase in the jump latency time with ED50's of 2 and 2.4 mg/kg for the disulfides of methioninethiol [H2NCH(CH2CH2SCH3)CH2S]2 and S-oxomethioninethiol [H2NCH(CH2CH2S(O)CH3)CH2S]2, respectively. These results show that the disulfide forms of beta-amino thiols are efficient prodrugs of aminopeptidase N inhibitors capable of crossing the blood-brain barrier.

  DOI：

  10.1021/jm00085a013
• 作为产物：
  描述：

  ((R)-2-tert-Butylsulfanyl-1-hydroxymethyl-ethyl)-carbamic acid tert-butyl ester 、 硫代乙酸 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 生成 Thioacetic acid S-((S)-2-tert-butoxycarbonylamino-3-tert-butylsulfanyl-propyl) ester
  参考文献：
  名称：

  Potent and systemically active aminopeptidase N inhibitors designed from active-site investigation

  摘要：

  Derivatives of amino acids bearing various zinc-coordinating moieties (SH, COOH, CONHOH, and PO3H2) were synthesized and tested for their ability to inhibit aminopeptidase N (APN). Among them, beta-amino thiols were found to be the most efficient with IC50's in the 11-50 nM range. These results suggest that the S1 subsite of APN is a deep but not very large hydrophobic pocket, optimally fitting side chains of moderate bulk endowed with some degree of freedom. The iv administration of the inhibitors, alone, did not induce antinociceptive responses on the hot plate test in mice. However, in presence of 10 mg/kg acetorphan, a prodrug of the neutral endopeptidase inhibitor thiorphan, these compounds gave a large increase in the jump latency time with ED50's of 2 and 2.4 mg/kg for the disulfides of methioninethiol [H2NCH(CH2CH2SCH3)CH2S]2 and S-oxomethioninethiol [H2NCH(CH2CH2S(O)CH3)CH2S]2, respectively. These results show that the disulfide forms of beta-amino thiols are efficient prodrugs of aminopeptidase N inhibitors capable of crossing the blood-brain barrier.

  DOI：

  10.1021/jm00085a013