L-组氨酸乙酯 | 7555-06-8

• 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: L-组氨酸乙酯
• 英文名称: ethyl 2-amino-3-(1H-imidazol-4-yl)propanoate
• 英文别名: L-histidine ethyl ester；histidine ethyl ester；L-Histidin-aethylester；Ethyl L-histidinate；ethyl (2S)-2-amino-3-(1H-imidazol-5-yl)propanoate
• CAS: 7555-06-8
• 化学式: C₈H₁₃N₃O₂
• mdl: MFCD12796099
• 分子量: 183.21
• InChiKey: ACHWEOLUTJAHLV-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  81
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933290090

反应信息

• 作为反应物：
  描述：

  L-组氨酸乙酯 在 bee venom 、 磷酸二脂酶 水 作用下， 以 水 、 异丙醇 为溶剂， 反应 12.0h， 生成 (2S)-2-[[(carboxymethylamino)methyl-methylphosphoryl]amino]-3-(1H-imidazol-5-yl)propanoic acid
  参考文献：
  名称：

  天然1-氨基羧酸和肽的有机磷类似物和衍生物vii。酶合成的phospha-c肽

  摘要：

  已经证明，可以通过酶催化烷基膦酸和二烷基次膦酸的酯与Lα-氨基羧酸的酯的缩合反应来获得磷酸C肽（具有PONH而不是CONH键）。自然膦的缩合，甲基膦酸酯1 - 4和甘氨酸，L-丙氨酸，L-甲硫氨酸和L-组氨酸的乙酯是在碱性磷酸酶的存在下进行（与酯1和2）和磷酸二酯酶I（与酯3和4）分别给出phospha-C肽5 – 20。游离二肽21 – 36的合成通过使用总蜂毒水解保护基团来实现。一个类似的过程应用到二肽37和38（通过用N-乙酰基的酶催化剂的碱性mesintericopeptidase选择性水解而获得的9和17和膦组分）4，得到磷-C三肽39 - 42，以及与甘氨酸酐分别为四肽43和44。

  DOI：

  10.1016/s0040-4020(01)86380-8
• 作为产物：
  描述：

  乙醇 、 L-组氨酸 在 potassium hydroxide 作用下， 反应 2.0h， 以72.1%的产率得到L-组氨酸乙酯
  参考文献：
  名称：

  The Study of the Effect of Histidine Derivatives as a Novel Antinociceptive and Anti-Inflammatory Activity

  摘要：

  这项研究解释了组氨酸衍生物的生化活性。该化合物通过CHN分析、FT-IR和H1 NMR鉴定。结果证实了所制备化合物的化学结构。通过两种不同的测试，即热板测试和蠕动测试评估镇痛活性，以及两种抗炎测试，即福尔马林诱导的炎症测试和卡拉胶诱导的炎症测试，研究了抗炎和镇痛活性。发现组氨酸衍生物具有强大的抗炎和镇痛活性。活性化合物进行了急性毒性测试。发现在小鼠口服5克/千克的剂量下，它们是安全的，没有任何死亡。

  DOI：

  10.1155/2011/173149

文献信息

• Facile and Mild Synthesis of Linear and Cyclic Peptides via Thioesters
  作者：Paola Agrigento、Fernando Albericio、Sylvie Chamoin、Isabelle Dacquignies、Halil Koc、Martin Eberle

  DOI：10.1021/ol501669n

  日期：2014.8.1

  Thioester-mediated peptide bond formation has recently garnered a lot of attention, most notably in its relevance to condensation of large peptide fragments. Herein, a simple and general ligation method for the preparation of linear and cyclic peptides, starting from peptide thioester, mainly p-chlorophenyl, precursors is reported. The inherent advantages of this method are the low epimerization, reduced

  硫酯介导的肽键形成近来引起了很多关注，尤其是与大肽片段缩合有关。在本文中，报道了一种简单且通用的制备线性和环状肽的方法，该方法从肽硫酯，主要是对氯苯基前体开始。该方法的固有优点是低差向异构化，减少的二聚化，使用温和的反应条件以及消除了多余的偶联剂。
• Benzoxazolamines and Benzothiazolamines: Potent, Enantioselective Inhibitors of Leukotriene Biosynthesis with a Novel Mechanism of Action
  作者：Edward S. Lazer、Clara K. Miao、Hin-Chor Wong、Ronald Sorcek、Denice M. Spero、Alex Gilman、Kollol Pal、Mark Behnke、Anne G. Graham

  DOI：10.1021/jm00033a008

  日期：1994.4

  phenylalanine with a cyclohexyl group greatly enhance potency. Several ester bioisosteres that retain potency and enantiomeric selectivity are described. Lead optimization culminated in (S)-N-[2-cyclohexyl-1-(2-pyridinyl)ethyl]-5-methyl-2-benzoxazolamine+ ++ (43b), IC50 0.001 microM. The compounds described are not inhibitors of 5-lipoxygenase but, rather, act at the level of arachidonic acid release.

  描述了一系列抑制白三烯（LT）生物合成的苯并恶唑胺和苯并噻唑胺类似物。最初的铅（S）-N-（苯并噻唑-2-基）苯丙氨酸乙酯（5a）在筛选程序中被发现，该程序可抑制Ca-离子载体-A23187诱导的人多形核白细胞释放LTB4（IC50 0.23 microM ）。通过结构修饰，确定了5-位上的疏水取代基以及苯丙氨酸的苯环被环己基取代极大地增强了效能。描述了几种保留效力和对映异构体选择性的酯类生物甾体。铅优化最终达到（S）-N- [2-环己基-1-（2-吡啶基）乙基] -5-甲基-2-苯并恶唑胺+ ++（43b），IC50 0.001 microM。所述化合物不是5-脂氧合酶的抑制剂，而是
• Polyglutamic Acids Functionalised by Histidine Derivatives and Hydrophobic Groups and the Uses Thereof, in Particular for Therapeutic Purposes
  申请人：Soula Olivier

  公开号：US20100034886A1

  公开（公告）日：2010-02-11

  The invention relates to novel biodegradable materials based on modified polyamino acids and suitable, in particular, for vectoring active substance(s) (AS). Said invention also relates to novel pharmaceutical, cosmetic, dietary or plant protective compositions which are based on said polyamino acids. The aim of said invention is to provide a novel polymer raw material usable for vectoring the AS and capable to optimally meet all specification in this area: biocompatibility, biodegradability, ability to become easily associated with many active substances or to solubilise them and to release said active substances in vivo. The aim is attained to 30 carbon atoms. Said polyglutamates modified by histidine derivatives are soluble with pH lower than 5 and are easily and economically convertible into active substance vectorization particles which are able to form stable aqueous colloidal suspensions. On the contrary, said modified polyglutamates are insoluble in water with a physiological pH (7.4), and thereby have to be precipitated on an injection site in the case of a subcutaneous injection.

  该发明涉及基于改性聚氨基酸的新型可生物降解材料，特别适用于载荷活性物质（AS）。该发明还涉及基于这些聚氨基酸的新型药用、化妆品、膳食或植物保护组合物。 该发明的目的是提供一种新型聚合物原料，可用于载荷AS，并能够最佳地满足该领域的所有规范要求：生物相容性、生物降解性、能够轻松与许多活性物质结合或溶解它们，并在体内释放所述活性物质。该目的在30个碳原子处实现。 通过组氨酸衍生物改性的聚谷氨酸在pH低于5时可溶解，并且可以经济地转化为能够形成稳定水性胶体悬浮液的活性物质载体颗粒。相反，这些改性聚谷氨酸在生理pH值（7.4）下不溶于水，因此在皮下注射时必须在注射部位沉淀。
• Bifunctionalized polysaccharides
  申请人：Soula Gerard

  公开号：US20080014250A1

  公开（公告）日：2008-01-17

  The present invention relates to a dextran and/or dextran derivative bifunctionalized by at least one imidazolyl radical Im and at least one hydrophobic group Hy, the said radical and the said group being each identical and/or different and grafted or bonded to the dextran and/or dextran derivative via one or more connecting arms R, Ri or Rh and functional groups F, Fi or Fh and the pharmaceutical compositions comprising one of the said dextrans and at least one active principle.

  本发明涉及一种由至少一个咪唑基团Im和至少一个疏水基团Hy双官能化的葡聚糖和/或葡聚糖衍生物，所述基团和所述基团各自相同和/或不同，并通过一个或多个连接臂R、Ri或Rh和功能基团F、Fi或Fh嫁接或结合到葡聚糖和/或葡聚糖衍生物上，并且所述药物组合物包括所述葡聚糖之一和至少一个活性成分。
• Preparation of prodrugs for selective drug delivery
  申请人：Mills L. Randell

  公开号：US20050080260A1

  公开（公告）日：2005-04-14

  Synthesis of a chemical compound having the formula A-B-C that may serve for applications such as drug delivery where A is a chemiluminescent, moiety, B is a photochromic moiety, and C is a biologically active moiety where A-B-C may serve as a prodrug. Novel synthetic methods of the present invention to form the prodrug comprised the steps of (1) forming a benzophenone, (2) forming a diaryl ethylene, (3) attaching a phthalimide moiety to at least one of the aryl groups of the ethylene to form a phthalimide-ethylene conjugate, (4) condensing two ethylene-phthalimide conjugates to form a phthalimide-pentadiene conjugate, (5) converting the phthalimide to the phthalhydrazide by reaction with hydrazine to form a carrier compound according to the present invention, and (6) reacting the carrier compound with an nucleophilic moiety of the drug to form the corresponding prodrug. Alternatively the carrier can be prepared by using the halo-substituted diaryl ethylene to make the corresponding cationic leuco dye-like compound with known methods. The cationic compound then is protected by reacting with a nucleophile and coupled with the aminophathalimide by palladium-catalyzed amination to form the protected phthalimide-pentadiene conjugate. The latter is refluxed with hydrazine to convert its phthalimide to the phthalhydrazide and acidified to give the carrier. An additional aspect of the present invention relates to the use of these compounds as antiviral agents for the treatment of viral infections such as HIV and as anticancer agents for the treatment of cancers such as bowel, lung, and breast cancer.

  合成具有A-B-C化学式的化合物，可用于药物传递等应用，其中A是化学发光基团，B是光致变色基团，C是生物活性基团，其中A-B-C可作为前药。本发明的新型合成方法用于形成前药，包括以下步骤：(1)形成苯酮，(2)形成二芳基乙烯，(3)将邻苯二甲酰亚胺基团连接到乙烯的至少一个芳基上，形成邻苯二甲酰亚胺-乙烯共轭物，(4)缩合两个乙烯-邻苯二甲酰亚胺共轭物，形成邻苯二甲酰亚胺-戊二烯共轭物，(5)通过与肼反应将邻苯二甲酰亚胺转化为邻苯二酰肼，形成本发明的载体化合物，(6)将载体化合物与药物的亲核基团反应，形成相应的前药。另外，可以通过使用卤代二芳基乙烯制备相应的阳离子类似的类似类似染料化合物。然后，通过与亲核试剂反应保护阳离子类似化合物，并通过钯催化的胺化与氨基邻苯二甲酰亚胺偶联，形成保护的邻苯二甲酰亚胺-戊二烯共轭物。后者与肼回流，将其邻苯二甲酰亚胺转化为邻苯二酰肼，并酸化以得到载体。本发明的另一个方面涉及将这些化合物用作抗病毒剂，用于治疗病毒感染，如HIV，以及用作抗癌剂，用于治疗结肠癌、肺癌和乳腺癌等癌症。