H-Glu(OBzl)-Glu(OBzl)-OBzl | 82082-83-5

• 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-Glu(OBzl)-Glu(OBzl)-OBzl
• 英文别名: H-Glu(Bzl)-Glu(Bzl)-OBzl；dibenzyl (2S)-2-[[(2S)-2-amino-5-oxo-5-phenylmethoxypentanoyl]amino]pentanedioate
• CAS: 82082-83-5
• 化学式: C₃₁H₃₄N₂O₇
• 分子量: 546.62
• InChiKey: PQDRSYJFXSDWDR-SVBPBHIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  40
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  H-Glu(OBzl)-Glu(OBzl)-OBzl 在 盐酸 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 (S)-2-{(S)-4-Benzyloxycarbonyl-2-[(S)-4-benzyloxycarbonyl-2-((S)-4-benzyloxycarbonyl-2-octanoylamino-butyrylamino)-butyrylamino]-butyrylamino}-pentanedioic acid dibenzyl ester
  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
• 作为产物：
  描述：

  dibenzyl (2S)-2-[[(2S)-2-[(4-methoxyphenyl)methoxycarbonylamino]-5-oxo-5-phenylmethoxypentanoyl]amino]pentanedioate 在 三氟乙酸 作用下， 以 various solvent(s) 为溶剂， 反应 1.0h， 生成 H-Glu(OBzl)-Glu(OBzl)-OBzl
  参考文献：
  名称：

  Kimachi, Tetsutaro; Kawase, Masahiro; Matsuki, Shinsuke, Journal of the Chemical Society. Perkin transactions I, 1990, # 2, p. 253 - 256

  摘要：

  DOI：

文献信息

• 一种聚乙二醇偶联药物、其制备方法及应用
  申请人：重庆阿普格雷生物科技有限公司

  公开号：CN112843242A

  公开（公告）日：2021-05-28

  本发明涉及医药技术领域，涉及一种聚乙二醇偶联药物、其制备方法及应用，具体涉及如式I所示的聚乙二醇偶联药物或其药学上可接受的盐。本发明还涉及所述聚乙二醇偶联药物或其药学上可接受的盐的制备方法，包含所述聚乙二醇偶联药物或其药学上可接受的盐的药物组合物和在制备药物中的用途。
• CONJUGATES OF WATER SOLUBLE POLYMER-AMINO ACID OLIGOPEPTIDE-DRUG, PREPARATION METHOD AND USE THEREOF
  申请人：JENKEM TECHNOLOGY CO. LTD. TIANJIN BRANCH

  公开号：US20150359900A1

  公开（公告）日：2015-12-17

  A conjugate of water soluble polymer-amino acid oligopeptide-drug of Formula (I) below and a pharmaceutical composition comprising the conjugate are provided. In the conjugate, P is a water soluble polymer; X is a linking group, wherein the linking group links P and A 1 ; each of A 1 , A 2 and A 3 is independently same or different amino acid residue or amino acid analogue residue; each of D 1 and D 2 is independently same or different drug molecule residue; a is 0 or 1; b is an integer of 2-12; c is an integer of 0-7; d is 0 or 1. The conjugate could improve drug load capacity, water solubility, stability and activity of the drug.

  提供一种水溶性聚合物-氨基酸寡肽-药物的共轭物，其化学式（I）如下，并提供包含该共轭物的制药组合物。在该共轭物中，P是水溶性聚合物；X是一个连接基团，连接基团连接P和A1；A1、A2和A3中的每一个独立地是相同或不同的氨基酸残基或氨基酸类似物残基；D1和D2中的每一个独立地是相同或不同的药物分子残基；a为0或1；b是2-12的整数；c是0-7的整数；d为0或1。该共轭物能够提高药物的载荷能力、水溶性、稳定性和活性。
• Synthesis and Preliminary Evaluation of Novel Bone-targeting NSAIDs Prodrugs based on Glutamic Acid Oligopeptides
  作者：Yi Zhao、Dongsheng He、Lifang Ma、Li Guo

  DOI：10.2174/1570180812999150217171229

  日期：2015.6.6

  Osteoarthritis is no doubt a difficult disease to manage. Targeted delivery of drugs to bone may not only enhance the treatment efficacy, but also reduces the quantity of drug administered. In this paper, we have synthesized two series of NSAID-Glu oligopeptide conjugates built up by the therapeutic moiety (naproxen and ibuprofen) and the targeting moieties (Glutamic oligopeptides) via amide linkage, as novel potential bone-targeting NSAIDs prodrugs. Preliminary studies indicated that these prodrugs exhibited outstanding hydroxyapatite affinity, furthermore, NSAIDs-glutamic hexa-peptide conjugates were found more potent in hydroxyapatite binding. The adequate chemical stability of the conjugates in different buffers, indicated that the conjugates might become a promising approach of selective delivery of drugs to bone tissues. These results may be conducive to the study of bone targeting drugs delivery.

  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。
• POLYETHYLENE GLYCOL CONJUGATED DRUG AND ITS PREPARATION METHOD AND USE
  申请人：CHONGQING UPGRA BIOTECHNOLOGY CO., LTD.

  公开号：US20220105189A1

  公开（公告）日：2022-04-07

  The disclosure relates to the technical field of medicine and in particular to a polyethylene glycol conjugated drug of formula I or a pharmaceutically acceptable salt thereof. The disclosure further relates to a method for preparation and an intermediate of the polyethylene glycol conjugated drug or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising the polyethylene glycol conjugated drug or a pharmaceutically acceptable salt thereof, and use of the polyethylene glycol conjugated drug or a pharmaceutically acceptable salt thereof in preparation of a medicament.

  本公开涉及医学技术领域，特别涉及公式I的聚乙二醇偶联药物或其药学上可接受的盐。本公开进一步涉及聚乙二醇偶联药物或其药学上可接受的盐的制备方法和中间体，包含聚乙二醇偶联药物或其药学上可接受的盐的制药组合物，以及在制备药物时使用聚乙二醇偶联药物或其药学上可接受的盐。
• 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.