2,5-二氧代-1-吡咯烷基N,1-二{[(2-甲基-2-丙基)氧基]羰基}-L-组氨酸酯 | 25616-02-8

• 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: 2,5-二氧代-1-吡咯烷基N,1-二{[(2-甲基-2-丙基)氧基]羰基}-L-组氨酸酯
• 英文名称: Boc-His(Boc)-OSu
• 英文别名: Boc-His (1-Boc)-OSU；Boc-L-His(1-Boc)-Osu；Boc-His(1-Boc)-Osu；tert-butyl 4-[(2S)-3-(2,5-dioxopyrrolidin-1-yl)oxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxopropyl]imidazole-1-carboxylate
• CAS: 25616-02-8
• 化学式: C₂₀H₂₈N₄O₈
• 分子量: 452.464
• InChiKey: LHFSCSBQQOTTRW-ZDUSSCGKSA-N

物化性质

• 熔点：
  >118°C (dec.)
• 溶解度：
  可溶于DMSO（少许）、乙酸乙酯（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  146
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2,5-二氧代-1-吡咯烷基N,1-二{[(2-甲基-2-丙基)氧基]羰基}-L-组氨酸酯 在 溶剂黄146 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 47.0h， 生成 {(S)-1-[(S)-1-((1S,2S,4S)-4-Butylcarbamoyl-1-cyclohexylmethyl-2-hydroxy-5-methyl-hexylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  C-Terminal modifications of nonpeptide renin inhibitors: improved oral bioavailability via modification of physicochemical properties

  摘要：

  We describe the development of a series of soluble, potent, and bioavailable nonpeptide renin inhibitors. These inhibitors derived from a series of novel nonpeptide renin inhibitors which were recently identified in our laboratories, by alteration of the nature of the C-terminus (P2') of the molecules. Introduction of basic substituents into modified hydroxyethylene dipeptide isosteres gave inhibitors with improved solubility as well as improved potency against human plasma renin. In addition, these modifications produced inhibitors which displayed markedly improved intraduodenal bioavailability in both the ferret and cynomolgus monkey. We also present data which demonstrate excellent efficacy in the monkey for A-74273 (65), with an intraduodenal bioavailability of 16 +/- 4% in the monkey, compared to 1.7 +/- 0.5% for the dipeptide renin inhibitor enalkiren (A-64662, 75). A-74273 is an example of a nonpeptide inhibitor which possesses a good balance of the desirable properties of potency, solubility, and lipophilicity and which is well absorbed into the intestine.

  DOI：

  10.1021/jm00088a007
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 N,N'-二叔丁氧羰基-L-组氨酸 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 生成 2,5-二氧代-1-吡咯烷基N,1-二{[(2-甲基-2-丙基)氧基]羰基}-L-组氨酸酯
  参考文献：
  名称：

  Molecular recognition of a tris(histidine) ligand

  摘要：

  本文介绍了设计与合成一种三汞配合物，以选择性识别三组（组氨酸）配体的方法。

  DOI：

  10.1039/a706711i

文献信息

• Synthesis, self-assembly, and catalytic activity of histidine-based structured lipopeptides for hydrolysis reactions in water
  作者：M. Bélières、N. Chouini-Lalanne、C. Déjugnat

  DOI：10.1039/c5ra02853a

  日期：——

  A new series of lipopeptides was designed to study their organocatalytic properties towards ester hydrolysis and the role of their self-assembled structures in catalysis. Synthesis of the catalysts was achieved by grafting fatty chains on tripeptides either at the C-terminal position or at the N-terminal extremity, affording amphiphilic character and self-assembling properties. Insertion of a histidine

  设计了一系列新的脂肽，以研究其对酯水解的有机催化性能以及其自组装结构在催化中的作用。催化剂的合成是通过将脂肪链接枝在C端或N端的三肽上实现的，具有两亲性和自组装特性。选择在肽序列中插入组氨酸以产生有机催化活性。首先通过确定临界聚集体浓度，然后通过表征通过散射技术和显微镜观察形成的聚集体，来证明自组织。结构的变化（肽序列，疏水特性）导致形成各种聚集体，从球状物体到纤维。水溶液中的乙酸对硝基苯酯。通过显示在单体和聚集体之间观察到的不同行为，证明了自组织对催化的影响。
• Aminoalkyl adenylate and aminoacyl sulfamate intermediate analogues differing greatly in affinity for their cognate Staphylococcus aureus aminoacyl tRNA synthetases
  作者：Andrew K. Forrest、Richard L. Jarvest、Lucy M. Mensah、Peter J. O'Hanlon、Andrew J. Pope、Robert J. Sheppard

  DOI：10.1016/s0960-894x(00)00360-7

  日期：2000.8

  histidine and threonine, have been prepared and tested as inhibitors of their cognate Staphylococcus aureus aminoacyl tRNA synthetases. The arginyl derivatives were both potent nanomolar inhibitors of the Class I arginyl tRNA synthetase whereas for the Class II histidyl and threonyl tRNA synthetases, the acyl sulfamates were potent inhibitors but the adenylates had very little affinity.

  制备了精氨酸，组氨酸和苏氨酸衍生的氨基烷基腺苷酸和氨基酰基氨基磺酸盐，并对其同源金黄色葡萄球菌氨基酰基tRNA合成酶的抑制剂进行了测试。精氨酰基衍生物都是I类精氨酰基tRNA合成酶的有效纳摩尔抑制剂，而对于II类组氨酸和苏氨酰基tRNA合成酶而言，酰基氨基磺酸盐是有效的抑制剂，但腺苷酸的亲和力很小。
• Functional profiling of adenylation domains in nonribosomal peptide synthetases by competitive activity-based protein profiling
  作者：Shota Kasai、Sho Konno、Fumihiro Ishikawa、Hideaki Kakeya

  DOI：10.1039/c5cc04953a

  日期：——

  Using a library of sulfamoyloxy-linked aminoacyl-AMP analogs, we describe competitive activity-based protein profiling to facilitate directly the functional prediction and assessment of adenylation domains in nonribosomal peptide synthetases in proteomic environments.

  利用磺胺氧基连接的氨酰-AMP类似物库，我们描述了竞争性活性蛋白质分析技术，以直接促进在蛋白质组学环境中对非核糖体肽合成酶中腺苷化结构域的功能预测和评估。
• Aminoacyl prodrug derivatives and medicaments for treatment of thromboembolic disorders
  申请人：Lerchen Hans-Georg

  公开号：US20100292230A1

  公开（公告）日：2010-11-18

  The present application relates to prodrug derivatives of 5-chloro-N-((5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide, processes for their preparation, their use for the treatment and/or prophylaxis of diseases, and their use for the manufacture of medicaments for the treatment and/or prophylaxis of diseases, especially of thromboembolic disorders.

  本申请涉及5-氯-N-((5S)-2-氧代-3-[4-(3-氧代吗啡啉-4-基)苯基]-1,3-噁唑烷-5-基}甲基)噻吩-2-羧酰胺的前药衍生物，其制备方法，它们用于治疗和/或预防疾病，以及它们用于制造用于治疗和/或预防疾病的药物，特别是用于治疗和/或预防血栓栓塞性疾病。
• [EN] AGENTS FOR IMPROVED DELIVERY OF NUCLEIC ACIDS TO EUKARYOTIC CELLS<br/>[FR] AGENTS POUR UNE ADMINISTRATION AMÉLIORÉE D'ACIDES NUCLÉIQUES À DES CELLULES EUCARYOTES
  申请人：MOLECULAR TRANSFER INC

  公开号：WO2012142622A1

  公开（公告）日：2012-10-18

  New cationic lipids are provided that are useful for delivering macromolecules, such as nucleic acids, into eukaryotic cells. The lipids can be used alone, in combination with other lipids and/or in combination with other transfection enhancing reagents to prepare transfection complexes.

  提供了新的阳离子脂质，可用于将大分子（如核酸）传递到真核细胞中。这些脂质可以单独使用，与其他脂质和/或其他转染增强试剂结合使用，制备转染复合物。