H-6-OBzl | 180973-86-8

• 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
• 英文名称: H-6-OBzl
• CAS: 180973-86-8
• 化学式: C₇₉H₈₆N₆O₁₉
• 分子量: 1423.58
• InChiKey: FXMOKCBKQGLPDE-WQJIKIKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.62
• 重原子数：
  104.0
• 可旋转键数：
  43.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  355.62
• 氢给体数：
  6.0
• 氢受体数：
  20.0

反应信息

• 作为反应物：
  描述：

  布洛芬 、 H-6-OBzl 在 N-甲基吗啉 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 0.08h， 生成
  参考文献：
  名称：

  Synthesis and Preliminary Evaluation of Novel Bone-targeting NSAIDs Prodrugs based on Glutamic Acid Oligopeptides

  摘要：

  骨关节炎无疑是一种难以治疗的疾病。向骨骼靶向给药不仅能提高疗效，还能减少给药量。本文合成了两个系列的非甾体抗炎药-谷氨酸低聚肽共轭物，这两个共轭物由治疗分子（萘普生和布洛芬）和靶向分子（谷氨酸低聚肽）通过酰胺连接而成，是潜在的新型骨靶向非甾体抗炎药原药。初步研究表明，这些原药具有出色的羟基磷灰石亲和力，而且非甾体抗炎药-谷氨酸六肽共轭物的羟基磷灰石结合力更强。这些共轭物在不同的缓冲液中具有足够的化学稳定性，这表明这些共轭物可能会成为向骨组织选择性给药的一种有前途的方法。这些结果可能有助于研究骨靶向给药。

  DOI：

  10.2174/1570180812999150217171229
• 作为产物：
  描述：

  在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 生成 H-6-OBzl
  参考文献：
  名称：

  Theβ-Type Structures of Very SimpleN-Octanoyl-L-glutamic Acid Oligomers (Residue Number,N= 2—6) and Theirβ₁→β₂-Type Transition

  摘要：

  为了研究 N-辛酰-谷氨酸低聚物（残基数 N = 2-6）在固态下的分子构象，我们合成了这些低聚物。研究了这些低聚物的 X 射线粉末衍射图样和振动光谱，并将其与聚-l-谷氨酸的 α 螺旋构象和 β 片状构象进行了比较。在这些低聚物的新鲜样品中，四聚体、五聚体和六聚体的构象与聚-l-谷氨酸的 β1 型相似。然而，这些低聚物的 β1 型构象在室温下随着时间的推移迅速转变为 β2 型构象，这表明即使在四聚体、五聚体和六聚体中也发生了类似于聚-l-谷氨酸的 β1→β2 转变。对于二聚体和三聚体的新鲜样品来说，这些分子都具有 β2-型结构。这意味着形成 β1→β2 型转变的低聚物的临界大小是四聚体。

  DOI：

  10.1246/bcsj.66.2196

文献信息

• Supramolecular aggregates formed by L-glutamic acid-oligomers: SANS and SAXS studies of the hydrogen bonded self-assembly
  作者：M. Ishida、M. Takai、H. Okabayashi、H. Masuda、M. Furusaka、C. J. O'Connor

  DOI：10.1039/b100717n

  日期：——

  N-Acetyl-L-glutamic acid oligomeric benzyl esters with various residue numbers (Np = 4, 5, 6, 8, 10, 12 and 14) have been synthesized by a stepwise procedure. The microstructures of these oligopeptide aggregates in dioxane or benzene have been investigated by IR, small angle neutron scattering (SANS), and small angle X-ray scattering (SAXS) spectra. It has been confirmed from the IR spectral data that preferential stabilization of antiparallel-type β-sheet structures occurs above the critical aggregation concentration and that the population of this antiparallel β-sheet increases with an increase in concentration. On the basis of these IR results, the model of the rod-like aggregate, in which the disk-like β-sheet monomers are one-dimensionally stacked antiparallel to each other, has been presented for analysis of the observed SANS and SAXS intensity profiles. The best fit intensity profiles, calculated with variation only of the aggregation number and with fixed molecular parameters based on the assumption of polydispersity, have furnished the monomer–monomer bond energies (ακT), corresponding to the hydrogen bonding energies, the number-average aggregation numbers, and the number-average molecular weights for these oligopeptide aggregates. Thus, the rod-like aggregates, formed by these oligopeptides in dioxane or benzene, can be regarded as supramolecular aggregates.

  N-乙酰-L-谷氨酸低聚苄酯具有不同的残基数（Np=4、5、6、8、10、12和14），通过逐步合成得到。通过红外光谱、小角中子散射（SANS）和小角X射线散射（SAXS）光谱，研究了这些二氧六环或苯中的寡肽聚合物的微观结构。红外光谱数据证实，在临界聚集浓度以上，反平行β-片层结构优先稳定，并且这种反平行β-片层数量随着浓度的增加而增加。根据这些红外结果，提出了棒状聚合物的模型，其中盘状β-片层单体彼此一维堆积，反平行排列，用于分析观察到的SANS和SAXS强度分布。根据多分散性的假设，仅改变聚集数并固定分子参数，计算出最佳拟合强度分布，从而得到单体-单体键能（ακT），对应于氢键能、数均聚集数和这些寡肽聚合物的数均分子质量。因此，这些寡肽在二氧六环或苯中形成的棒状聚合物，可被视为超分子聚合物。
• Dual-targeting liposome modified by glutamic hexapeptide and folic acid for bone metastatic breast cancer
  作者：Yang Yang、Ze Zhao、Changwei Xie、Yi Zhao

  DOI：10.1016/j.chemphyslip.2020.104882

  日期：2020.5

  Bone is the most common organ affected by metastatic breast cancer. Targeting delivery of drugs to bone may not only enhance the treatment efficacy, but also reduce the quantity of drug administered. In order to increase the distribution of paclitaxel (PTX) in bone, herein, a novel bone metastasis-targeted glutamic hexapeptide-folic acid (Glu(6)-FA) derivative was designed and synthesized as liposome ligand to deliver PTX to bone metastasis effectively. The liposomes were prepared by thin film hydration method and its particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis were also characterized. What's more, the antitumor effects of PTX-Glu(6)-FA-Lip were confirmed by the detection of cell cycle, migration, and further measurement of microtubule stabilization. In addition, the PTX-Glu(6)-FA-Lip showed superior targeting ability in vitro and in vivo evaluation as compared to naked PTX, non-coated, singly-modified and co-modified by physical blending liposomes. All the results suggested that Glu(6)-FA-modified liposome showed excellent targeting activity to metastatic bone cancer. These findings suggested that Glu(6)-FA-Lip was a promising bone metastasis-targeting carrier for the delivery of PTX. This study may therefore be conducive to the field of bone-targeting drugs delivery.