3,6-bis{[(S)-2,2-dimethyl-1,3-dioxolan-4-yl]methylamino}pyrazine-2,5-dicarboxamide | 1313706-20-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3,6-bis{[(S)-2,2-dimethyl-1,3-dioxolan-4-yl]methylamino}pyrazine-2,5-dicarboxamide
• 英文别名: 3,6-bis[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methylamino]pyrazine-2,5-dicarboxamide
• CAS: 1313706-20-5
• 化学式: C₁₈H₂₈N₆O₆
• 分子量: 424.457
• InChiKey: BTWIMBOJLCXVQX-UWVGGRQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  173
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  3,6-bis{[(S)-2,2-dimethyl-1,3-dioxolan-4-yl]methylamino}pyrazine-2,5-dicarboxamide 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 以68%的产率得到3,6-bis[(S)-2,3-dihydroxypropylamino]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-dicarboxamide 、 (R)-(+)-2,2-二甲基-1,3-二氧戊环-4-甲醛 在 溶剂黄146 、 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 3,6-bis{[(S)-2,2-dimethyl-1,3-dioxolan-4-yl]methylamino}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.