dimethyl [(3S)-3-[N-(tert-butoxycarbonyl)amino]-5-hydroxy-2-oxopentyl]phosphonate | 768395-80-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: dimethyl [(3S)-3-[N-(tert-butoxycarbonyl)amino]-5-hydroxy-2-oxopentyl]phosphonate
• 英文别名: tert-butyl N-[(3S)-1-dimethoxyphosphoryl-5-hydroxy-2-oxopentan-3-yl]carbamate
• CAS: 768395-80-8
• 化学式: C₁₂H₂₄NO₇P
• 分子量: 325.299
• InChiKey: ZQFGZZHRZBYNQI-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  dimethyl [(3S)-3-[N-(tert-butoxycarbonyl)amino]-5-hydroxy-2-oxopentyl]phosphonate 在 palladium on activated charcoal 重铬酸吡啶 、 氢气 、 caesium carbonate 、 三乙胺 、 lithium chloride 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 12.5h， 生成 benzyl (3R/S)-6-(tert-butoxycarbonyl)-3-[N-(tert-butoxycarbonyl)amino]-4-oxo-hexanoate
  参考文献：
  名称：

  Dipeptidomimetic Ketomethylene Isosteres as Pro-moieties for Drug Transport via the Human Intestinal Di-/Tripeptide Transporter hPEPT1:  Design, Synthesis, Stability, and Biological Investigations

  摘要：

  Five dipeptidomimetic-based model prodrugs containing ketomethylene amide bond replacements were synthesized from readily available alpha,beta-unsaturated gamma-ketoesters. The model drug (BnOH) was attached to the C-terminus or to one of the side chain positions of the dipeptidomimetic. The stability, the affinity for the di-/tripeptide transporter hPEPT1, and the transepithelial transport properties of the model prodrugs were investigated. ValPsi[COCH2]-Asp(OBn) was the compound with highest chemical stability in buffers at pH 6.0 and 7.4, with half-lives of 190 and 43 h, respectively. All five compounds showed high affinity for hPEPT1 (K-i values < 1 mM), and PhePsi[COCH2]Asp(OBn) and ValPsi[COCH2]Asp(OBn) had the highest affinities with K-i values of 68 and 19 muM, respectively. Am hPEPT1-mediated transport component was demonstrated for the transepithelial transport of three compounds, a finding that was corroborated by hPEPT1-mediated intracellular uptake. The results indicate that the stabilized Phe-Asp and Val-Asp derivatives are promising pro-moieties in a prodrug approach targeting hPEPT1.

  DOI：

  10.1021/jm040780c
• 作为产物：
  描述：

  (S)-(-)-alpha-(Boc-氨基)-gamma-丁酸内酯 、 甲基膦酸二甲酯 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.5h， 以48%的产率得到dimethyl [(3S)-3-[N-(tert-butoxycarbonyl)amino]-5-hydroxy-2-oxopentyl]phosphonate
  参考文献：
  名称：

  Dipeptidomimetic Ketomethylene Isosteres as Pro-moieties for Drug Transport via the Human Intestinal Di-/Tripeptide Transporter hPEPT1:  Design, Synthesis, Stability, and Biological Investigations

  摘要：

  Five dipeptidomimetic-based model prodrugs containing ketomethylene amide bond replacements were synthesized from readily available alpha,beta-unsaturated gamma-ketoesters. The model drug (BnOH) was attached to the C-terminus or to one of the side chain positions of the dipeptidomimetic. The stability, the affinity for the di-/tripeptide transporter hPEPT1, and the transepithelial transport properties of the model prodrugs were investigated. ValPsi[COCH2]-Asp(OBn) was the compound with highest chemical stability in buffers at pH 6.0 and 7.4, with half-lives of 190 and 43 h, respectively. All five compounds showed high affinity for hPEPT1 (K-i values < 1 mM), and PhePsi[COCH2]Asp(OBn) and ValPsi[COCH2]Asp(OBn) had the highest affinities with K-i values of 68 and 19 muM, respectively. Am hPEPT1-mediated transport component was demonstrated for the transepithelial transport of three compounds, a finding that was corroborated by hPEPT1-mediated intracellular uptake. The results indicate that the stabilized Phe-Asp and Val-Asp derivatives are promising pro-moieties in a prodrug approach targeting hPEPT1.

  DOI：

  10.1021/jm040780c

文献信息

• Dipeptidomimetic Ketomethylene Isosteres as Pro-moieties for Drug Transport via the Human Intestinal Di-/Tripeptide Transporter hPEPT1:  Design, Synthesis, Stability, and Biological Investigations
  作者：Jon Våbenø、Carsten Uhd Nielsen、Truls Ingebrigtsen、Tore Lejon、Bente Steffansen、Kristina Luthman

  DOI：10.1021/jm040780c

  日期：2004.9.1

  Five dipeptidomimetic-based model prodrugs containing ketomethylene amide bond replacements were synthesized from readily available alpha,beta-unsaturated gamma-ketoesters. The model drug (BnOH) was attached to the C-terminus or to one of the side chain positions of the dipeptidomimetic. The stability, the affinity for the di-/tripeptide transporter hPEPT1, and the transepithelial transport properties of the model prodrugs were investigated. ValPsi[COCH2]-Asp(OBn) was the compound with highest chemical stability in buffers at pH 6.0 and 7.4, with half-lives of 190 and 43 h, respectively. All five compounds showed high affinity for hPEPT1 (K-i values < 1 mM), and PhePsi[COCH2]Asp(OBn) and ValPsi[COCH2]Asp(OBn) had the highest affinities with K-i values of 68 and 19 muM, respectively. Am hPEPT1-mediated transport component was demonstrated for the transepithelial transport of three compounds, a finding that was corroborated by hPEPT1-mediated intracellular uptake. The results indicate that the stabilized Phe-Asp and Val-Asp derivatives are promising pro-moieties in a prodrug approach targeting hPEPT1.