(2S)-2-amino-6-[[(E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoyl]amino]hexanoic acid | 1253696-85-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (2S)-2-amino-6-[[(E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoyl]amino]hexanoic acid
• CAS: 1253696-85-3
• 化学式: C₁₆H₂₂N₂O₅
• 分子量: 322.361
• InChiKey: VHOPIWUPYREUSE-WMADIVHISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  122
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  甲醇 、 (2S)-2-amino-6-[[(E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoyl]amino]hexanoic acid 在 氯化亚砜 作用下， 以72%的产率得到methyl (2S)-2-amino-6-[[(E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoyl]amino]hexanoate
  参考文献：
  名称：

  含有反式阿魏酸的L-赖氨酸前药，用于5-氨基水杨酸结肠递送：合成，表征和体外抗氧化活性评估。

  摘要：

  在目前的工作中，我们报告了可用于克罗恩病治疗的新型5-氨基水杨酸（5-ASA）前药的合成及其抗氧化活性的评估。使用L-赖氨酸氨基酸作为药理学载体，并利用其固有的化学反应性，由于存在两个手性中心和ε位的氨基，我们将反阿魏酸插入ε位酰胺化反应，用甲醇酯化羧基，最后将游离氨基与5-ASA（炎性肠病（IBD）护理的主要药物）进行重氮化。所有合成中间体和最终产物（衍生物A）均采用常用的光谱技术进行表征，如FT-IR，GC / MS和（1）H-MNR。最后，衍生物A的抗氧化剂活性，通过两种不同来源的自由基2,2'-偶氮双（2-ami基丙烷）（AAPH）和叔丁基氢过氧化物（叔胺）体外诱导抑制大鼠肝脏微粒体膜中的脂质过氧化-BOOH），进行了评估。我们的前药既可以作为5-ASA的前药，也可以作为反式阿魏酸的载体成功应用于制药领域。

  DOI：

  10.1248/cpb.58.103
• 作为产物：
  描述：

  L-赖氨酸盐酸盐 、 ferulic acid chloride 在 copper(II) carbonate 、 potassium hydroxide 、 8-羟基喹啉 作用下， 以 水 、 丙酮 、 氯仿 为溶剂， 生成 (2S)-2-amino-6-[[(E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoyl]amino]hexanoic acid
  参考文献：
  名称：

  Synthesis of pro-prodrugs l-lysine based for 5-aminosalicylic acid and 6-mercaptopurine colon specific release

  摘要：

  The aim of this work is to design, prepare and characterize L-lysine based prodrugs capable of targeting 6-mercaptopurine to the colon, an anti-tumor and immunosuppressant drug, and 5-aminosalicylic acid (5-ASA), drug of choice for inflammatory bowel disease (IBD). More specifically, Ne-feruloyl-S-(6-purinyl)-L-lysine and Ne-acryloyl-S-(6-purinyl)-L-lysine were synthesized and then characterized by FT-IR, H-1-NMR and GC/MS spectroscopies. The ability of feruloyl derivative in inhibiting lipid peroxidation in rat liver microsomal membranes, induced in vitro by tert-butyl hydroperoxide as source of free radicals, was evaluated. Moreover, N epsilon-acryloyl-S-(6-purinyl)-L-lysine, polymerizable prodrug, was used to microspheres realization for 5-ASA release. These lasts, obtained by emulsion inverse technique, were characterized by light scattering and scanning electron microscopy (SEM) analysis. The microspheres equilibrium swelling degree was evaluated and showed good swelling behaviour in simulating colonic fluids. Results confirm the possibility that the application range of L-lysine prodrug can be extended to the treatment of intestinal diseases whose conventional therapy envisages medications with serious side effects that, thanks to this new strategy, can be minimized in an optimal way. (c) 2011 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ijpharm.2011.09.001

文献信息

• L-Lysine Pro-Prodrug Containing trans-Ferulic Acid for 5-Amino Salicylic Acid Colon Delivery: Synthesis, Characterization and in Vitro Antioxidant Activity Evaluation
  作者：Roberta Cassano、Sonia Trombino、Alessia Cilea、Teresa Ferrarelli、Rita Muzzalupo、Nevio Picci

  DOI：10.1248/cpb.58.103

  日期：——

  report the synthesis of a new 5-amino salicylic acid (5-ASA) pro-prodrug, useful in Crohn disease treatment, and the evaluation of its antioxidant activity. Using as pharmacological carrier L-lysine amino acid and taking advantage of its intrinsic chemical reactivity, due to the presence of two amino groups, placed on the chiral center and in epsilon-position, we inserted trans-ferulic acid in epsilon-position

  在目前的工作中，我们报告了可用于克罗恩病治疗的新型5-氨基水杨酸（5-ASA）前药的合成及其抗氧化活性的评估。使用L-赖氨酸氨基酸作为药理学载体，并利用其固有的化学反应性，由于存在两个手性中心和ε位的氨基，我们将反阿魏酸插入ε位酰胺化反应，用甲醇酯化羧基，最后将游离氨基与5-ASA（炎性肠病（IBD）护理的主要药物）进行重氮化。所有合成中间体和最终产物（衍生物A）均采用常用的光谱技术进行表征，如FT-IR，GC / MS和（1）H-MNR。最后，衍生物A的抗氧化剂活性，通过两种不同来源的自由基2,2'-偶氮双（2-ami基丙烷）（AAPH）和叔丁基氢过氧化物（叔胺）体外诱导抑制大鼠肝脏微粒体膜中的脂质过氧化-BOOH），进行了评估。我们的前药既可以作为5-ASA的前药，也可以作为反式阿魏酸的载体成功应用于制药领域。
• Synthesis of pro-prodrugs l-lysine based for 5-aminosalicylic acid and 6-mercaptopurine colon specific release
  作者：Sonia Trombino、Roberta Cassano、Alessia Cilea、Teresa Ferrarelli、Rita Muzzalupo、Nevio Picci

  DOI：10.1016/j.ijpharm.2011.09.001

  日期：2011.11

  The aim of this work is to design, prepare and characterize L-lysine based prodrugs capable of targeting 6-mercaptopurine to the colon, an anti-tumor and immunosuppressant drug, and 5-aminosalicylic acid (5-ASA), drug of choice for inflammatory bowel disease (IBD). More specifically, Ne-feruloyl-S-(6-purinyl)-L-lysine and Ne-acryloyl-S-(6-purinyl)-L-lysine were synthesized and then characterized by FT-IR, H-1-NMR and GC/MS spectroscopies. The ability of feruloyl derivative in inhibiting lipid peroxidation in rat liver microsomal membranes, induced in vitro by tert-butyl hydroperoxide as source of free radicals, was evaluated. Moreover, N epsilon-acryloyl-S-(6-purinyl)-L-lysine, polymerizable prodrug, was used to microspheres realization for 5-ASA release. These lasts, obtained by emulsion inverse technique, were characterized by light scattering and scanning electron microscopy (SEM) analysis. The microspheres equilibrium swelling degree was evaluated and showed good swelling behaviour in simulating colonic fluids. Results confirm the possibility that the application range of L-lysine prodrug can be extended to the treatment of intestinal diseases whose conventional therapy envisages medications with serious side effects that, thanks to this new strategy, can be minimized in an optimal way. (c) 2011 Elsevier B.V. All rights reserved.