benzyl (3R,6S)-3-(tert-butoxycarbonyl)-6-[N-(tert-butoxycarbonyl)amino]-7-methyl-5-oxo-octanoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl (3R,6S)-3-(tert-butoxycarbonyl)-6-[N-(tert-butoxycarbonyl)amino]-7-methyl-5-oxo-octanoate
• 英文别名: 4-O-benzyl 1-O-tert-butyl (2R)-2-[(3S)-4-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]-2-oxopentyl]butanedioate
• 化学式: C₂₆H₃₉NO₇
• 分子量: 477.598
• InChiKey: DDXRKDXWRHWSCA-KNQAVFIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  34
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  乙酸苄酯 在 四氢吡咯 、 四(三苯基膦)钯 、 sodium hydride 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲苯 、 xylene 为溶剂， 反应 17.0h， 生成 benzyl (3R,6S)-3-(tert-butoxycarbonyl)-6-[N-(tert-butoxycarbonyl)amino]-7-methyl-5-oxo-octanoate
  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.