5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[4-(bis-Boc-guanidine)butoxy]calix[4]arene | 883561-30-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[4-(bis-Boc-guanidine)butoxy]calix[4]arene
• CAS: 883561-30-6
• 化学式: C₁₀₄H₁₆₄N₁₂O₂₀
• 分子量: 1902.51
• InChiKey: WSGIIQSROHJDJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  27.9
• 重原子数：
  136
• 可旋转键数：
  52
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  393
• 氢给体数：
  8
• 氢受体数：
  24

反应信息

• 作为反应物：
  描述：

  5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[4-(bis-Boc-guanidine)butoxy]calix[4]arene 在 盐酸 、 三乙基硅烷 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以36%的产率得到
  参考文献：
  名称：

  两亲胍基杯芳烃抑制脂多糖（LPS）和凝集素刺激的Toll样受体4（TLR4）信号传导。

  摘要：

  我们最近报道了阳离子两亲物在抑制TLR4活化以及随后在细胞和动物模型中产生炎性细胞因子的活性。从适当设计的阳离子两亲物可以充当CD14 / MD-2配体并因此调节TLR4信号的假设出发，我们在此介绍一组两亲性胍基杯芳烃，其结构在计算上经过优化，可与MD-2和CD14结合位点对接。这些杯芳烃中的一些在以剂量依赖性方式抑制人和小鼠细胞中LPS刺激的TLR4活化和TLR4依赖性细胞因子产生方面具有活性。此外，当TLR4被非LPS刺激（植物凝集素PHA）激活时，胍基杯芳烃也抑制TLR4信号传导。

  DOI：

  10.1021/acs.jmedchem.7b00095
• 作为产物：
  描述：

  N,N'-bis-Boc-S-methyl-isothiourea 、 5,11,17,23-Tetra-p-tert-butyl-25,26,27,28-tetrakis<(aminobutyl)oxy>calix<4>arene 在 三乙胺 、 mercury dichloride 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以29%的产率得到5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrakis[4-(bis-Boc-guanidine)butoxy]calix[4]arene
  参考文献：
  名称：

  [EN] CALIXARENE-BASED PEPTIDE CONFORMATION MIMETICS, METHODS OF USE, AND METHODS OF MAKING
  [FR] MIMETIQUES A CONFORMATION PEPTIDIQUE A BASE DE CALIXARENE, PROCEDES D'UTILISATION, ET PROCEDES D'ELABORATION

  摘要：

  公开号：

  WO2006042104A3

文献信息

• Topomimetics of Amphipathic β-Sheet and Helix-Forming Bactericidal Peptides Neutralize Lipopolysaccharide Endotoxins
  作者：Xuemei Chen、Ruud P. M. Dings、Irina Nesmelova、Stefan Debbert、Judith R. Haseman、Jacques Maxwell、Thomas R. Hoye、Kevin H. Mayo

  DOI：10.1021/jm0610447

  日期：2006.12.1

  Release of lipopolysaccharide (LPS) endotoxin from Gram negative bacterial membranes triggers macrophages to produce large quantities of cytokines that can lead to septic shock and eventual death. Agents that bind to and neutralize LPS may provide a means to clinically prevent septic shock upon bacterial infection. Previously, we reported the design of antibacterial helix peptide SC4 and beta-sheet-forming beta pep peptides that neutralize LPS in vitro. We hypothesized that the ability of these and other such peptides to neutralize LPS rested in the common denominator of positively charged amphipathic structure. Here, we describe the design and synthesis of nonpeptide, calixarene-based helix/sheet topomimetics that mimic the folded conformations of these peptides in their molecular dimensions, amphipathic surface topology, and compositional properties. From a small library of topomimetics, we identified several compounds that neutralize LPS in the 10(-8) M range, making them as effective as bactericidal/permeability increasing protein and polymyxin B. In an endotoxemia mouse model, three of the most in vitro effective topomimetics are shown to be at least partially protective against challenges of LPS from different bacterial species. NMR studies provide mechanistic insight by suggesting the site of molecular interaction between topomimetics and the lipid A component of LPS, with binding being mediated by electrostatic and hydrophobic interactions. This research contributes to the development of pharmaceutical agents against endotoxemia and septic shock.
• [EN] CALIXARENE-BASED PEPTIDE CONFORMATION MIMETICS, METHODS OF USE, AND METHODS OF MAKING<br/>[FR] MIMETIQUES A CONFORMATION PEPTIDIQUE A BASE DE CALIXARENE, PROCEDES D'UTILISATION, ET PROCEDES D'ELABORATION
  申请人：UNIV MINNESOTA

  公开号：WO2006042104A3

  公开（公告）日：2007-01-18
• Amphiphilic Guanidinocalixarenes Inhibit Lipopolysaccharide (LPS)- and Lectin-Stimulated Toll-like Receptor 4 (TLR4) Signaling
  作者：Stefania E. Sestito、Fabio A. Facchini、Ilaria Morbioli、Jean-Marc Billod、Sonsoles Martin-Santamaria、Alessandro Casnati、Francesco Sansone、Francesco Peri

  DOI：10.1021/acs.jmedchem.7b00095

  日期：2017.6.22

  optimized to dock into MD-2 and CD14 binding sites. Some of these calixarenes were active in inhibiting, in a dose-dependent way, the LPS-stimulated TLR4 activation and TLR4-dependent cytokine production in human and mouse cells. Moreover, guanidinocalixarenes also inhibited TLR4 signaling when TLR4 was activated by a non-LPS stimulus, the plant lectin PHA. While the activity of guanidinocalixarenes

  我们最近报道了阳离子两亲物在抑制TLR4活化以及随后在细胞和动物模型中产生炎性细胞因子的活性。从适当设计的阳离子两亲物可以充当CD14 / MD-2配体并因此调节TLR4信号的假设出发，我们在此介绍一组两亲性胍基杯芳烃，其结构在计算上经过优化，可与MD-2和CD14结合位点对接。这些杯芳烃中的一些在以剂量依赖性方式抑制人和小鼠细胞中LPS刺激的TLR4活化和TLR4依赖性细胞因子产生方面具有活性。此外，当TLR4被非LPS刺激（植物凝集素PHA）激活时，胍基杯芳烃也抑制TLR4信号传导。