N2,N5-bis[(R)-1-(benzyloxy)-3-hydroxy-1-oxopropan-2-yl]-3,6-bis(propylamino)pyrazine-2,5-dicarboxamide | 1313706-18-1

• 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: N2,N5-bis[(R)-1-(benzyloxy)-3-hydroxy-1-oxopropan-2-yl]-3,6-bis(propylamino)pyrazine-2,5-dicarboxamide
• 英文别名: benzyl (2R)-3-hydroxy-2-[[5-[[(2R)-3-hydroxy-1-oxo-1-phenylmethoxypropan-2-yl]carbamoyl]-3,6-bis(propylamino)pyrazine-2-carbonyl]amino]propanoate
• CAS: 1313706-18-1
• 化学式: C₃₂H₄₀N₆O₈
• 分子量: 636.705
• InChiKey: HVJCQWLPZFWPSL-DNQXCXABSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  46
• 可旋转键数：
  20
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  201
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  N2,N5-bis[(R)-1-(benzyloxy)-3-hydroxy-1-oxopropan-2-yl]-3,6-bis(propylamino)pyrazine-2,5-dicarboxamide 在 palladium 10% on activated carbon 、 甲酸铵 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 以71%的产率得到N2,N5-bis[(R)-1,3-dihydroxy-1-oxopropan-2-yl]-3,6-bis(propylamino)pyrazine-2,5-dicarboxamide
  参考文献：
  名称：

  Hydrophilic Pyrazine Dyes as Exogenous Fluorescent Tracer Agents for Real-Time Point-of-Care Measurement of Glomerular Filtration Rate

  摘要：

  Various hydrophilic pyrazine-bis(carboxamides) derived from 3,5-diamino-pyrazine-2,5-dicarboxylic acid bearing neutral and anionic groups were prepared and evaluated for use as fluorescent glomerular filtration rate (GFR) tracer agents. Among these, the dianionic D-serine pyrazine derivatives 2d and 2j, and the neutral dihydroxypropyl 2h, exhibited favorable physicochemical and clearance properties. In vitro studies show that 2d, 2h, and 2j have low plasma protein binding, a necessary condition for renal excretion. In vivo animal model results show that these three compounds exhibit a plasma clearance equivalent to iothalamate (a commonly considered gold standard GFR agent). In addition, these compounds have a higher urine recovery compared to iothalamate. Finally, the plasma clearance of 2d, 2h, and 2j remained unchanged upon blockage of the tubular secretion pathway with probenecid, a necessary condition for establishment of clearance via glomerular filtration only. Hence, 2d, 2h, and 2j are promising candidates for translation to the clinic as exogenous fluorescent tracer agents in real-time point-of-care monitoring of GFR.

  DOI：

  10.1021/jm200257k
• 作为产物：
  描述：

  3,6-diaminopyrazine-2,5-dicarboxylic acid 在 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.75h， 生成 N2,N5-bis[(R)-1-(benzyloxy)-3-hydroxy-1-oxopropan-2-yl]-3,6-bis(propylamino)pyrazine-2,5-dicarboxamide
  参考文献：
  名称：

  Hydrophilic Pyrazine Dyes as Exogenous Fluorescent Tracer Agents for Real-Time Point-of-Care Measurement of Glomerular Filtration Rate

  摘要：

  Various hydrophilic pyrazine-bis(carboxamides) derived from 3,5-diamino-pyrazine-2,5-dicarboxylic acid bearing neutral and anionic groups were prepared and evaluated for use as fluorescent glomerular filtration rate (GFR) tracer agents. Among these, the dianionic D-serine pyrazine derivatives 2d and 2j, and the neutral dihydroxypropyl 2h, exhibited favorable physicochemical and clearance properties. In vitro studies show that 2d, 2h, and 2j have low plasma protein binding, a necessary condition for renal excretion. In vivo animal model results show that these three compounds exhibit a plasma clearance equivalent to iothalamate (a commonly considered gold standard GFR agent). In addition, these compounds have a higher urine recovery compared to iothalamate. Finally, the plasma clearance of 2d, 2h, and 2j remained unchanged upon blockage of the tubular secretion pathway with probenecid, a necessary condition for establishment of clearance via glomerular filtration only. Hence, 2d, 2h, and 2j are promising candidates for translation to the clinic as exogenous fluorescent tracer agents in real-time point-of-care monitoring of GFR.

  DOI：

  10.1021/jm200257k

文献信息

• Hydrophilic Pyrazine Dyes as Exogenous Fluorescent Tracer Agents for Real-Time Point-of-Care Measurement of Glomerular Filtration Rate
  作者：Raghavan Rajagopalan、William L. Neumann、Amruta R. Poreddy、Richard M. Fitch、John N. Freskos、Bethel Asmelash、Kimberly R. Gaston、Karen P. Galen、Jeng-Jong Shieh、Richard B. Dorshow

  DOI：10.1021/jm200257k

  日期：2011.7.28

  Various hydrophilic pyrazine-bis(carboxamides) derived from 3,5-diamino-pyrazine-2,5-dicarboxylic acid bearing neutral and anionic groups were prepared and evaluated for use as fluorescent glomerular filtration rate (GFR) tracer agents. Among these, the dianionic D-serine pyrazine derivatives 2d and 2j, and the neutral dihydroxypropyl 2h, exhibited favorable physicochemical and clearance properties. In vitro studies show that 2d, 2h, and 2j have low plasma protein binding, a necessary condition for renal excretion. In vivo animal model results show that these three compounds exhibit a plasma clearance equivalent to iothalamate (a commonly considered gold standard GFR agent). In addition, these compounds have a higher urine recovery compared to iothalamate. Finally, the plasma clearance of 2d, 2h, and 2j remained unchanged upon blockage of the tubular secretion pathway with probenecid, a necessary condition for establishment of clearance via glomerular filtration only. Hence, 2d, 2h, and 2j are promising candidates for translation to the clinic as exogenous fluorescent tracer agents in real-time point-of-care monitoring of GFR.