dibenzyl 2,2'-((3,6-diaminopyrazine-2,5-dicarbonyl)-bis(azanediyl)) (2R,2'R)-bis(3-hydroxypropanoate) | 1234369-93-7

• 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: dibenzyl 2,2'-((3,6-diaminopyrazine-2,5-dicarbonyl)-bis(azanediyl)) (2R,2'R)-bis(3-hydroxypropanoate)
• 英文别名: benzyl (2R)-2-[[3,6-diamino-5-[[(2R)-3-hydroxy-1-oxo-1-phenylmethoxypropan-2-yl]carbamoyl]pyrazine-2-carbonyl]amino]-3-hydroxypropanoate
• CAS: 1234369-93-7
• 化学式: C₂₆H₂₈N₆O₈
• 分子量: 552.544
• InChiKey: BPFWBDBHMFNDGC-QZTJIDSGSA-N

物化性质

• 沸点：
  871.0±65.0 °C(Predicted)
• 密度：
  1.437±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  40
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  229
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  3,6-diaminopyrazine-2,5-dicarboxylic acid 、 D-serine benzyl ester hydrochloride 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 以71%的产率得到dibenzyl 2,2'-((3,6-diaminopyrazine-2,5-dicarbonyl)-bis(azanediyl)) (2R,2'R)-bis(3-hydroxypropanoate)
  参考文献：
  名称：

  METHODS FOR RENAL FUNCTION DETERMINATION

  摘要：

  本公开涉及用于确定肾小球滤过率或评估患者肾功能的系统和方法。该方法包括向患者施用化合物I的吡嗪类化合物，并监测患者的肾脏从患者的全身循环中排除吡嗪的速率。当暴露于电磁辐射时，吡嗪化合物会发出荧光，使用一个或多个传感器来检测。患者体内荧光减少的速率被用来计算患者的肾小球滤过率。

  公开号：

  US20190125902A1

文献信息

• METHODS FOR RENAL FUNCTION DETERMINATION
  申请人：MediBeacon Inc.

  公开号：US20190125902A1

  公开（公告）日：2019-05-02

  The present disclosure relates to systems and methods for determining the renal glomerular filtration rate or assessing the renal function in a patient in need thereof. The method includes administering a pyrazine compound of Formula I to a patient 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 is detected using one or more sensors. The rate in which the fluorescence decreases in the patient is used to calculate the renal glomerular filtration rate in the patient.

  本公开涉及用于确定肾小球滤过率或评估患者肾功能的系统和方法。该方法包括向患者施用化合物I的吡嗪类化合物，并监测患者的肾脏从患者的全身循环中排除吡嗪的速率。当暴露于电磁辐射时，吡嗪化合物会发出荧光，使用一个或多个传感器来检测。患者体内荧光减少的速率被用来计算患者的肾小球滤过率。
• [EN] MODIFIED PYRAZINE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS MODIFIÉS DE PYRAZINE ET LEURS UTILISATIONS
  申请人：MALLINCKRODT INC

  公开号：WO2010078025A1

  公开（公告）日：2010-07-08

  Provided herein are compounds, preparations and formulations comprising pyrazine derivatives having multiple poly(ethylene glycol) containing substituents. Many of the compounds disclosed herein are excretable by the renal system of a subject or patient and are useful for visualizing the renal system of a subject or patient. Upon excitation by electromagnetic radiation, a number of the compounds disclosed herein exhibit luminescence and are externally detectable when present in the body fluid of a patient or subject. Also provided herein are methods for visualizing the renal system of a subject or patient.

  本文提供了含有多个聚乙二醇取代基的吡嗪衍生物的化合物、制剂和配方。其中许多化合物可通过受试者或患者的肾系统排泄，并可用于可视化受试者或患者的肾系统。在电磁辐射的激发下，本文披露的一些化合物表现出发光性，并在患者或受试者的体液中存在时可外部检测到。本文还提供了可视化受试者或患者的肾系统的方法。
• [EN] METHOD FOR PREPARING AND ANALYZING FLUORESCENT COMPOUNDS IN PLASMA<br/>[FR] PROCÉDÉ DE PRÉPARATION ET D'ANALYSE DE COMPOSÉS FLUORESCENTS DANS LE PLASMA
  申请人：MEDIBEACON INC

  公开号：WO2019099672A1

  公开（公告）日：2019-05-23

  Disclosed herein is a method for analyzing the concentration of a fluorescent compound in the plasma of a patient. The method includes collecting a sample of plasma from a patient, diluting the sample with a solvent and analyzing the diluted sample by HPLC. The sample does not need to be dried down during sample preparation nor is an internal standard required.

  本文公开了一种分析患者血浆中荧光化合物浓度的方法。该方法包括从患者采集血浆样本，用溶剂稀释样本并通过高效液相色谱分析稀释后的样本。在样品制备过程中，样品不需要干燥，也不需要内标。
• Modified Pyrazine Derivatives and Uses Thereof
  申请人：Poreddy Amruta

  公开号：US20140186267A1

  公开（公告）日：2014-07-03

  Provided herein are compounds, preparations and formulations comprising pyrazine derivatives having multiple poly(ethylene glycol) containing substituents. Many of the compounds disclosed herein are excretable by the renal system of a subject or patient and are useful for visualizing the renal system of a subject or patient. Upon excitation by electromagnetic radiation, a number of the compounds disclosed herein exhibit luminescence and are externally detectable when present in the body fluid of a patient or subject. Also provided herein are methods for visualizing the renal system of a subject or patient.

  本文提供了含有多个聚乙二醇取代基的吡嗪衍生物的化合物、制剂和配方。本文披露的许多化合物可被患者的肾系统排泄，并可用于可视化患者的肾系统。在电磁辐射的激发下，本文披露的一些化合物表现出发光性，并在患者或受试者的体液中存在时可外部检测。本文还提供了可视化受试者或患者肾系统的方法。
• [EN] HYDROGENATION SYNTHESIS METHOD FOR PREPARING PYRAZINECARBOXYLIC ACID DERIVATIVE AS FLUORESCENT TRACER<br/>[FR] PROCÉDÉ DE SYNTHÈSE PAR HYDROGÉNATION POUR PRÉPARER UN DÉRIVÉ D'ACIDE PYRAZINECARBOXYLIQUE UTILISÉ EN TANT QUE TRACEUR FLUORESCENT<br/>[ZH] 用于制备作为荧光示踪剂的吡嗪羧酸类衍生物的氢化合成方法
  申请人：[en]HANGZHOU ZHONGMEIHUADONG PHARMACEUTICAL CO., LTD.;[zh]杭州中美华东制药有限公司

  公开号：WO2023046046A1

  公开（公告）日：2023-03-30

  涉及用于作为荧光示踪剂的吡嗪羧酸类衍生物的氢化合成方法，具体涉及制备3,6-二氨基-2,5-双N-[(1R)-1-羧基-2-羟基乙基]氨基甲酰基}吡嗪的方法,该方法避免使用易燃易爆的氢气，且解决了甲酸铵升华所致的堵塞管路的问题，大大降低了生产中的安全隐患。