tert-butyl N-[N'-[2-[(3aR,4S,7R,7aS)-1,3-dioxo-3a,4,7,7a-tetrahydro-4,7-epoxyisoindol-2-yl]ethyl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate | 1045594-31-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: tert-butyl N-[N'-[2-[(3aR,4S,7R,7aS)-1,3-dioxo-3a,4,7,7a-tetrahydro-4,7-epoxyisoindol-2-yl]ethyl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate
• CAS: 1045594-31-7
• 化学式: C₂₁H₃₀N₄O₇
• 分子量: 450.492
• InChiKey: COSXJAUESLUERR-KPWCQOOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[N'-[2-[(3aR,4S,7R,7aS)-1,3-dioxo-3a,4,7,7a-tetrahydro-4,7-epoxyisoindol-2-yl]ethyl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate 、 third generation Grubbs catalyst 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Stimuli-Responsive Polyguanidino-Oxanorbornene Membrane Transporters as Multicomponent Sensors in Complex Matrices

  摘要：

  We introduce guanidinium-containing synthetic polymers based on polyguanidino-oxanorbornenes (PGONs) as anion transporters in lipid bilayers that can be activated and inactivated by chemical stimulation. According to fluorogenic anion export experiments with vesicles, PGON transporters are most active in neutral bilayers near their phase transition, with EC50's in the nanomolar range. Six times higher effective transporter concentrations were measured with aminonaphthalene-1,3,6-trisulfonate than with 5(6)-carboxyfluorescein, demonstrating the importance of anion binding for transport and excluding nonspecific efflux. Negative surface potentials efficiently annihilate transport activity, while inside-negative membrane potentials slightly increase it. These trends demonstrate the functional importance of counterions to hinder the binding of hydrophilic counterions and to minimize the global positive charge of the transporter-counterion complexes. Strong, nonlinear increases in activity with polymer length reveal a significant polymer effect. Overall, the characteristics of PGONs do not match those of similar systems (for example, polyarginine) and hint toward an interesting mode of action, clearly different from nonspecific leakage caused by detergents. The activity of PGONs increases in the presence of amphiphilic anions such as pyrenebutyrate (EC50 = 70 mu M), while several other amphiphilic anions tested were inactive. PGONs are efficiently inactivated by numerous hydrophilic anions including ATP (IC50 = 150 mu M), ADP (IC50 = 460 mu M), heparin (IC50 = 1.0 mu M), phytate (IC50 = 0.4 mu M), and CB hydrazide (IC50 = 26 mu M). The compatibility of this broad responsiveness with multicomponent sensing in complex matrices is discussed and illustrated with lactate sensing in sour milk. The PGON lactate sensor operates together with lactate oxidase as a specific signal generator and CB hydrazide as an amplifier for covalent capture of the pyruvate product as CB hydrazone (IC50 = 1.5 mu M).

  DOI：

  10.1021/ja802587j
• 作为产物：
  描述：

  exo-7-oxabicyclo[2.2.1]hept-4-ene-2,3-dicarboximide 在 偶氮二甲酸二异丙酯 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 15.0h， 生成 tert-butyl N-[N'-[2-[(3aR,4S,7R,7aS)-1,3-dioxo-3a,4,7,7a-tetrahydro-4,7-epoxyisoindol-2-yl]ethyl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate
  参考文献：
  名称：

  具有结构修饰的π电子的含芳香物质的细胞穿透肽模拟物的设计

  摘要：

  细胞穿透肽（CPPs）及其合成模拟物（CPPMs）代表了一类分子，可促进细胞内各种货物的递送。先前的研究表明，芳香族官能团的存在改善了CPPM的活性。鉴于芳香族官能团在膜生物学中起着重要作用并参与各种π相互作用，我们探讨了这些相互作用是否可以优化以提高CPPM活性。CPPM是通过开环复分解聚合反应合成的，该聚合反应使用的单体包含被给电子和吸电子基团取代的芳环，且静电势范围为-29.69至+15.57 kcal mol -1。这些基团改变了芳族体系的四极矩，并用于测试这种结构修饰是否改变了CPPM活性。将CPPM添加到载有染料的囊泡中，并根据聚合物浓度监测羧基荧光素的释放。监测释放50％染料的有效聚合物浓度的变化（有效浓度，EC 50）。该测定的结果表明，CPPM中结合的给电子和吸电子基团的强度不会改变聚合物的EC 50价值观或活动。这表明其他设计参数可能会对CPPM活动产生更大的影响。另外

  DOI：

  10.1002/chem.201405381

文献信息

• Protein Transduction Domain Mimics: The Role of Aromatic Functionality
  作者：Abhigyan Som、Anika Reuter、Gregory N. Tew

  DOI：10.1002/anie.201104624

  日期：2012.1.23

  For better or worse: Protein transduction domain mimics built from synthetic polymers demonstrate that aromatic side chains provide better transduction than aliphatic groups at the same relative hydrophobicity. Similarly, a less hydrophobic aromatic side chain is more active than the corresponding aliphatic one containing the same number of carbon atoms (see picture).

  不管好坏，由合成聚合物构建的蛋白质转导域模拟物表明，在相同的相对疏水性下，芳族侧链比脂族基团提供更好的转导。同样，疏水性较低的芳族侧链比相应的含相同碳原子数的脂肪族侧链更具活性（参见图片）。
• Protein transduction domains mimics
  申请人：Tew Gregory N.

  公开号：US09382366B2

  公开（公告）日：2016-07-05

  The invention generally relates to synthetic mimics of cell penetrating peptides. More particularly, the invention relates to certain novel monomers, oligomers and polymers (e.g., co-polymers) that are useful for the preparation of synthetic mimics of cell penetrating peptides, their compositions, preparations and use.

  这项发明通常涉及细胞穿透肽的合成模拟物。更具体地，该发明涉及某些新颖的单体、寡聚体和聚合物（例如，共聚物），这些物质可用于制备细胞穿透肽的合成模拟物，以及它们的组成、制备和用途。
• Effects of sidechain isomerism on polymer-based non-covalent protein delivery
  作者：Alfonso Barrios、Mario Milan、Elianny Perozo、Md Lokman Hossen、Prem Chapagain、Joong Ho Moon

  DOI：10.1039/d2cc02343a

  日期：——

  Polymer sidechain isomerism significantly influences intracellular protein delivery due to altered planarity of the functional group.

  由于侧链异构化引起的功能团平面性改变，聚合物侧链异构化显著影响细胞内蛋白质输送。
• Self-Activation in De Novo Designed Mimics of Cell-Penetrating Peptides
  作者：Abhigyan Som、A. Ozgul Tezgel、Gregory J. Gabriel、Gregory N. Tew

  DOI：10.1002/anie.201101535

  日期：2011.6.27
• Modified guanidine-containing polymers for biologic delivery
  申请人：Moon Joong Ho

  公开号：US11529315B1

  公开（公告）日：2022-12-20

  The subject invention provides materials and methods for intracellular deliver of molecules and/or therapeutic agents. The subject invention also provides methods for synthesizing polymeric systems and nanomaterials that enhance or assist the passage of molecules and/or therapeutic agents across biological membranes. The compound, polymer or nanoparticle of the subject invention comprises a modified guanidine moiety in a plurality of repeating units of a polymer or on the surface of a nanoparticle where the guanidine moiety comprises, for example, a carbamoyl or thiourea modification. The polymer or nanoparticle can be used in a cancer treatment formulation.