3,6,9,12-tetraoxatetradecane-1,14-dioic acid bis(2,5-dioxopyrrolidin-1-yl) ester | 211746-82-6

• 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: 3,6,9,12-tetraoxatetradecane-1,14-dioic acid bis(2,5-dioxopyrrolidin-1-yl) ester
• 英文别名: (2,5-Dioxopyrrolidin-1-yl) 2-[2-[2-[2-[2-(2,5-dioxopyrrolidin-1-yl)oxy-2-oxoethoxy]ethoxy]ethoxy]ethoxy]acetate
• CAS: 211746-82-6
• 化学式: C₁₈H₂₄N₂O₁₂
• 分子量: 460.395
• InChiKey: OLLVURODDAVHOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  32
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  164
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  单-6-O-氨基-Β-环糊精 、 3,6,9,12-tetraoxatetradecane-1,14-dioic acid bis(2,5-dioxopyrrolidin-1-yl) ester 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以18.5%的产率得到
  参考文献：
  名称：

  Specific Binding of a β-Cyclodextrin Dimer to the Amyloid β Peptide Modulates the Peptide Aggregation Process

  摘要：

  Alzheimer's disease involves progressive neuronal loss. Linked to the disease is the amyloid beta (A beta) peptide, a 38-43-amino acid peptide found in extracellular amyloid plaques in the brain. Cyclodextrins are nontoxic, cone-shaped oligosaccharides with a hydrophilic exterior and a hydrophobic cavity making them suitable hosts for aromatic guest molecules in water. beta-Cyclodextrin consists of seven alpha-D-glucopyranoside units and has been shown to reduce the level of fibrillation and neurotoxicity of A beta. We have studied the interaction between A beta and a beta-cyclodextrin dimer, consisting of two beta-cyclodextrin monomers connected by a flexible linker. The beta-cyclodextrin monomer has been found to interact with A beta(1-40) at sites Y10, F19, and/or F20 with a dissociation constant (K-D) of 3.9 +/- 2.0 mM. Here H-1-N-15 and H-1-C-13 heteronuclear single-quantum correlation nuclear magnetic resonance (NMR) spectra show that in addition, the beta-cyclodextrin monomer and dimer bind to the histidines. NMR translational diffusion experiments reveal the increased affinity of the beta-cyclodextrin dimer (apparent K-D of 1.1 +/- .5 mM) for A beta(1-40) compared to that of the beta-cyclodextrin monomer. Kinetic aggregation experiments based on thioflavin T fluorescence indicate that the dimer at 0.05-5 mM decreases the lag time of A beta aggregation, while a concentration of 10 mM increases the lag time. The beta-cyclodextrin monomer at a high concentration decreases the lag time of the aggregation. We conclude that cyclodextrin monomers and dimers have specific, modulating effects on the A beta(1-40) aggregation process. Transmission electron microscopy shows that the regular fibrillar aggregates formed by A beta(1-40) alone are replaced by a major fraction of amorphous aggregates in the presence of the beta-cyclodextrin dimer.

  DOI：

  10.1021/bi300341j
• 作为产物：
  描述：

  3,6,9,12-四氧杂十四烷-1,14-二甲酸 在 吡啶 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 3,6,9,12-tetraoxatetradecane-1,14-dioic acid bis(2,5-dioxopyrrolidin-1-yl) ester
  参考文献：
  名称：

  Ligand Recognition by E- and P-Selectin:  Chemoenzymatic Synthesis and Inhibitory Activity of Bivalent Sialyl Lewis x Derivatives and Sialyl Lewis x Carboxylic Acids

  摘要：

  Described is the preparation of five sLe(x) dimers and five sLe(x) carboxylic acids by coupling chemoenzymatically synthesized amino-substituted sialyl Lewis x (sLe(x)) derivative 4 to homobifunctional cross-linkers 20-24 of varying chain length. 20-24 were obtained by alkylating low-molecular-weight oligoethylene glycols with tert-butyl bromoacetate and subsequent transformation of the di-tert-butyl esters into disuccinimide esters. The products were assayed for inhibition against binding of a sLe(a)-polymer to immobilized E- and P-selectin. In the E-selectin assay all dimers had lower IC50 values than the sLex monomer. The results show that comparable binding enhancements can be obtained with linkers of completely different length and rigidity. In the P-selectin assay four of the five sLe(x) carboxylic acids displayed significantly improved inhibitory potency. The lowest IC50 value was observed for the compound with the shortest spacer between the sLex moiety and the additional carboxylate, being ca. 20-40 times more potent than unmodified sLex. These findings should be of importance for the design of new multivalent forms of sLe(x) as well as sLe(x) mimetics as high-affinity selectin ligands.

  DOI：

  10.1021/jo980350s

文献信息

• [EN] SELECTIN OR GALECTIN ANTAGONISTS FOR TREATING CYTOKINE RELEASE SYNDROME AND CRS-INDUCED NEUROTOXICITY<br/>[FR] ANTAGONISTES DE LA SÉLECTINE OU DE LA GALECTINE POUR LE TRAITEMENT DU SYNDROME DE LIBÉRATION DE LA CYTOKINE ET DE LA NEUROTOXICITÉ INDUITE PAR LE CRS
  申请人：MAGNANI JOHN L

  公开号：WO2020150263A1

  公开（公告）日：2020-07-23

  Methods and compounds for the treatment and/or prevention of CRS and/or CRS-induced neurotoxicities using at least one selectin antagonist are disclosed. The disclosed methods and compounds use at least one of the disclosed antagonists to target and reduce cytokine expression and/or endothelial activation to treat and/or prevent CRS and/or CRS-related conditions such as CRS-induced neurotoxicities.

  使用至少一种选择素拮抗剂治疗和/或预防CRS和/或CRS诱导的神经毒性的方法和化合物被披露。披露的方法和化合物使用至少一种披露的拮抗剂来靶向和减少细胞因子表达和/或内皮活化，以治疗和/或预防CRS和/或CRS相关症状，如CRS诱导的神经毒性。
• [EN] GALACTOSE-LINKED MULTIMERIC GLYCOMIMETIC INHIBITORS OF E-SELECTINS, GALECTIN-3, AND/OR CXCR4 CHEMOKINE RECEPTORS<br/>[FR] INHIBITEURS GLYCOMIMÉTIQUES MULTIMÈRES LIÉS AU GALACTOSE DE SÉLECTINES E, DE GALECTINE-3 ET/OU DE RÉCEPTEURS DE CHIMIOKINE CXCR4
  申请人：GLYCOMIMETICS INC

  公开号：WO2020219417A1

  公开（公告）日：2020-10-29

  Compounds, compositions, and methods for treating and/or preventing at least one disease, disorder, and/or condition associated with E-selectin, galectin-3, and/or CXCR4 chemokine receptor activity are disclosed herein. For example, multimeric glycomimetic inhibitors ofE-selectins, galectin-3, and/or CXCR4 chemokine receptors and their use for treating and/or preventing inflammatory diseases, fibrosis, and cancers are disclosed. Formula (I).

  本文揭示了用于治疗和/或预防与E-选择素、galectin-3和/或CXCR4趋化因子受体活性相关的至少一种疾病、紊乱和/或状况的化合物、组合物和方法。例如，本文揭示了用于治疗和/或预防炎症性疾病、纤维化和癌症的E-选择素、galectin-3和/或CXCR4趋化因子受体的多聚糖类似物抑制剂及其用途。公式（I）。
• Effective stabilisation of α-helical structures in short peptides with acetylenic cross-linking agents
  作者：Kazuhisa Fujimoto、Natsuko Oimoto、Kahori Katsuno、Masahiko Inouye

  DOI：10.1039/b403615h

  日期：——

  The peptides cross-linked by the acetylenic cross-linking agents showed high α-helical contents, and the α-helices thus formed survived up to substantially elevated temperature.

  用乙炔交联剂交联的肽显示出很高的δ-螺旋含量，由此形成的δ-螺旋在温度大幅升高的情况下仍能存活。
• [EN] METHODS OF TREATING HIV AND AIDS AND THE ELIMINATION OF LATENT RESERVOIRS OF HIV INFECTION USING SELECTIN, GALECTIN, AND SIGLEC ANTAGONISTS<br/>[FR] PROCÉDÉS POUR TRAITEMENT DU VIH ET DU SIDA ET ÉLIMINATION DE RÉSERVOIRS LATENTS D'UNE INFECTION PAR LE VIH À L'AIDE D'ANTAGONISTES DE LA SÉLECTINE, DE LA GALECTINE ET DE SIGLEC
  申请人：GLYCOMIMETICS INC

  公开号：WO2020123435A3

  公开（公告）日：2020-08-06
• WO2021022132A5
  申请人：——

  公开号：WO2021022132A5

  公开（公告）日：2023-07-28