(2S)-2-氨基-3-[4-(二(2-羟基乙基)氨基)苯基]丙酸 | 72143-20-5

• 物质功能分类: 医药中间体 - 原料药中间体
• 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
• 中文名称: (2S)-2-氨基-3-[4-(二(2-羟基乙基)氨基)苯基]丙酸
• 中文别名: 1-苯甲基-4-氰基-4-哌啶羧酸乙基酯
• 英文名称: 4-(bis-(2-hydroxyethyl)amino)-L-phenylalanine
• 英文别名: 4-(Bis-(2-hydroxyethyl)amino)-L-phenylalanin；4-Bis(2-hydroxyethyl)amino-L-phenylalanine；(2S)-2-amino-3-[4-[bis(2-hydroxyethyl)amino]phenyl]propanoic acid
• CAS: 72143-20-5
• 化学式: C₁₃H₂₀N₂O₄
• 分子量: 268.313
• InChiKey: WHGUXSYETMNGJA-LBPRGKRZSA-N

物化性质

• 沸点：
  519.6±50.0 °C(Predicted)
• 密度：
  1.318±0.06 g/cm3(Predicted)
• 溶解度：
  甲醇（微溶）、水（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  -3.1
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  107
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  美法仑 在 水 作用下， 生成 (2S)-2-氨基-3-[4-(二(2-羟基乙基)氨基)苯基]丙酸
  参考文献：
  名称：

  Imaging the DNA Alkylator Melphalan by CEST MRI: An Advanced Approach to Theranostics

  摘要：

  Brain tumors are among the most lethal types of tumors. Therapeutic response variability and failure in patients have been attributed to several factors, including inadequate drug delivery to tumors due to the blood-brain barrier (BBB). Consequently, drug delivery strategies are being developed for the local and targeted delivery of drugs to brain tumors. These drug delivery strategies could benefit from new approaches to monitor the delivery of drugs to tumors. Here, we evaluated the feasibility of imaging 4-[bis(2-chloroethyl)amino]-L-phenylalanine (melphalan), a clinically used DNA alkylating agent, using chemical exchange saturation transfer magnetic resonance imaging (CEST MRI), for theranostic applications. We evaluated the physicochemical parameters that affect melphalan's CEST contrast and demonstrated the feasibility of imaging the unmodified drug by saturating its exchangeable amine protons. Melphalan generated a CEST signal despite its reactivity in an aqueous milieu. The maximum CEST signal was observed at pH 6.2. This CEST contrast trend was then used to monitor therapeutic responses to melphalan in vitro. Upon cell death, the decrease in cellular pH from similar to 7.4 to similar to 6.4 caused an amplification of the melphalan CEST signal. This is contrary to what has been reported for other CEST contrast agents used for imaging cell death, where a decrease in the cellular pH following cell death results in a decrease in the CEST signal. Ultimately, this method could be used to noninvasively monitor melphalan delivery to brain tumors and also to validate therapeutic responses to melphalan clinically.

  DOI：

  10.1021/acs.molpharmaceut.6b00130

文献信息

• Analysis of novel melphalan hydrolysis products formed under isolated lung perfusion conditions using liquid chromatography/tandem mass spectrometry
  作者：Jasper Boschmans、Ernst de Bruijn、Paul Van Schil、Filip Lemière

  DOI：10.1002/rcm.6515

  日期：2013.4.15

  ultra-performance liquid chromatography (UPLC) tandem mass spectrometry (MS/MS). Aqueous melphalan solutions were incubated at elevated temperatures and analyzed by UPLC/MS/MS. Two previously described hydrolysis products, mono- and dihydroxymelphalan (MOH and DOH), were formed in vitro and could be characterized during MS/MS and high-resolution experiments. RESULTS Novel compounds with m/z values >500 Da

  RATIONALE Melphalan是在癌症治疗中被广泛使用的细胞毒剂。该苯丙氨酸类似物已被证明可有效治疗乳腺癌，多发性骨髓瘤和四肢黑色素瘤。对药物降解和代谢的充分了解对于了解其在癌症治疗过程中的活性至关重要。方法使用超高效液相色谱（UPLC）串联质谱（MS / MS）研究美法仑水解产物的形成。在高温下孵育美法仑水溶液，并通过UPLC / MS / MS进行分析。在体外形成了两种先前描述的水解产物，单和二羟基马法兰（MOH和DOH），可以在MS / MS和高分辨率实验中进行表征。结果发现了m / z值> 500 Da的新型化合物。这些新分子与MOH和DOH的断裂模式的比较显示出很大的相似性。较高的质量可以通过存在两个或多个马法兰单元来解释。总共发现了15种以上的新水解产物。建立实验来研究这些分子的形成和化学结构。结论在II期临床试验（隔离肺灌注，ILUP）的范围内研究了美法仑的水解。筛选
• An Improved Process for the Synthesis of Melphalan and the Hydrochloride Salt
  申请人：BIOPHORE INDIA PHARMACEUTICALS PVT. LTD.

  公开号：US20160016889A1

  公开（公告）日：2016-01-21

  The present invention relates to an improved process for the preparation of Melphalan, more specifically the invention relates to an efficient process for the preparation of substantially pure Melphalan hydrochloride (I).

  本发明涉及一种改进的甲氨蝶呤制备方法，更具体地说，该发明涉及一种高效的制备基本纯净的盐酸甲氨蝶呤（I）的方法。
• Process Of Making Optically Pure Melphalan
  申请人：Jobdevairakkam Christopher N.

  公开号：US20090240074A1

  公开（公告）日：2009-09-24

  This invention provides a process of making 4-(bis-(2-hydroxyethyl)amino)-L-phenylalanine of the formula by hydroxyethylation, in a regioselective manner, of the aromatic amino group rather than the glycinic amino group.

  该发明提供了一种制备4-(双(2-羟乙基)氨基)-L-苯丙氨酸的方法，通过对芳香族氨基而不是甘氨酸氨基进行区域选择性的羟乙基化。
• Process for the Synthesis of Melphalan and the Hydrochloride Salt
  申请人：Biophore India Pharmaceuticals PVT. Ltd.

  公开号：US20180237377A1

  公开（公告）日：2018-08-23

  The present invention relates to an improved process for the preparation of Melphalan, more specifically the invention relates to an efficient process for the preparation of substantially pure Melphalan hydrochloride (I).

  本发明涉及一种改进的甲氨蝶呤制备工艺，更具体地，本发明涉及一种高效的制备几乎纯甲氨蝶呤盐酸盐（I）的工艺。
• [EN] PROCESS OF MAKING OPTICALLY PURE MELPHALAN<br/>[FR] PROCÉDÉ PERMETTANT DE PRODUIRE DU MELPHALAN OPTIQUEMENT PUR
  申请人：NAVINTA LLC

  公开号：WO2009117164A1

  公开（公告）日：2009-09-24

  This invention provides a process of making 4-(bis-(2-hydroxyethyl)amino)-L-phenylalanine of the formula (I) by hydroxyethylation, in a regioselective manner, of the aromatic amino group rather than the glycinic amino group.

  本发明提供了一种制备4-（双（2-羟乙基）氨基）-L-苯丙氨酸式（I）的方法，通过对芳香族氨基而非甘氨酸氨基进行区域选择性的羟乙基化。