N2,N5-bis[(R)-1,3-dihydroxy-1-oxopropan-2-yl]-3,6-bis[(S)-2,3-dihydroxypropylamino]pyrazine-2,5-dicarboxamide | 1313706-29-4

• 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)-1,3-dihydroxy-1-oxopropan-2-yl]-3,6-bis[(S)-2,3-dihydroxypropylamino]pyrazine-2,5-dicarboxamide
• 英文别名: (2R)-2-[[5-[[(1R)-1-carboxy-2-hydroxyethyl]carbamoyl]-3,6-bis[[(2S)-2,3-dihydroxypropyl]amino]pyrazine-2-carbonyl]amino]-3-hydroxypropanoic acid
• CAS: 1313706-29-4
• 化学式: C₁₈H₂₈N₆O₁₂
• 分子量: 520.453
• InChiKey: NZLDFQBEYMPQLF-AXTSPUMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4
• 重原子数：
  36
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  304
• 氢给体数：
  12
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  dibenzyl 2,2'-((3,6-diaminopyrazine-2,5-dicarbonyl)-bis(azanediyl)) (2R,2'R)-bis(3-hydroxypropanoate) 在 盐酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 水 、 1,2-二氯乙烷 为溶剂， 反应 4.0h， 生成 N2,N5-bis[(R)-1,3-dihydroxy-1-oxopropan-2-yl]-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

文献信息

• SUBCUTANEOUS AND INTRAMUSCULAR ADMINISTRATION OF PYRAZINE COMPOUNDS
  申请人：MediBeacon Inc.

  公开号：US20220143222A1

  公开（公告）日：2022-05-12

  The present disclosure relates to methods for determining the renal glomerular filtration rate or assessing the renal function in a patient in need thereof. The method comprises administering, subcutaneously or intramuscularly, a pyrazine compound of Formula I to a patient, wherein the administration produces a plasma concentration of the compound that is substantially similar to a plasma concentration produced by intravenous administration of an identical amount of the compound; and monitoring the rate in which the kidneys of the patient eliminate the pyrazine from the systemic circulation of the patient. The pyrazine compound fluoresces when exposed to electromagnetic radiation which may be detected using one or more sensors. The rate in which the fluorescence decreases in the patient may be used to calculate the renal glomerular filtration rate in the patient.

  本公开涉及用于确定患者的肾小球滤过率或评估其肾功能的方法。该方法包括将式I的吡嗪化合物经皮下或肌肉注射给予患者，其中给药产生的化合物血浆浓度与相同量的化合物经静脉注射产生的血浆浓度基本相似；并监测患者肾脏从全身循环中清除吡嗪的速率。当吡嗪化合物暴露于电磁辐射时，其会发出荧光，可以使用一个或多个传感器检测。患者体内荧光减少的速率可以用于计算患者的肾小球滤过率。
• SENSOR ASSEMBLY WITH MOVABLE SKIN SENSOR
  申请人：MediBeacon Inc.

  公开号：US20210369164A1

  公开（公告）日：2021-12-02

  Disclosed herein is a housing assembly configured to attach to a body surface of a patient and comprising at least one opening; a skin sensor movably disposed in the at least one opening of the housing assembly; and wherein the housing assembly is configured to move independently relative to the skin sensor when an external force is applied to the housing assembly.
• SYSTEMS AND METHODS FOR HOME TRANSDERMAL ASSESSMENT OF GASTROINTESTINAL FUNCTION
  申请人：MediBeacon Inc.

  公开号：US20220022820A1

  公开（公告）日：2022-01-27

  Disclosed herein is a non-transitory computer-readable media having computer-executable instructions thereon. When executed by the processor of a mobile computing device, the computer-executable instructions cause the processor to wirelessly communicatively couple the mobile computing device to a GI sensor (optionally by displaying instructions on a pairing screen), display a sensor placement screen that instructs the user to place the GI sensor on a body of a patient, prompts the user to administer a GI agent into the body of the patient; transmit a signal from the mobile computing device to the GI sensor to cause the GI sensor to initiate collection of light absorbance data for calculating GI function of the patient; receive light absorbance data from the GI sensor, and store the received light absorbance data.
• 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.