N-(3-{(3β)-cholest-5-en-3-yl[(2-nitrophenyl)sulfonyl]amino}propyl)-6-(7-nitrobenzofurazan-4-ylamino)hexanamide | 828293-46-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: N-(3-{(3β)-cholest-5-en-3-yl[(2-nitrophenyl)sulfonyl]amino}propyl)-6-(7-nitrobenzofurazan-4-ylamino)hexanamide
• 英文别名: N-(3-{(3beta)-cholest-5-en-3-yl[(2-nitrophenyl)sulfonyl]amino}propyl)-6-(7-nitrobenzofurazan-4-ylamino)hexanamide；N-[3-[[(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl]-(2-nitrophenyl)sulfonylamino]propyl]-6-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]hexanamide
• CAS: 828293-46-5
• 化学式: C₄₈H₆₉N₇O₈S
• 分子量: 904.184
• InChiKey: AYTSAFQQROTSIU-WLIZTHHASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.3
• 重原子数：
  64
• 可旋转键数：
  19
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  217
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  N-(3-{(3β)-cholest-5-en-3-yl[(2-nitrophenyl)sulfonyl]amino}propyl)-6-(7-nitrobenzofurazan-4-ylamino)hexanamide 在 potassium carbonate 、 苯硫酚 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以29%的产率得到N-{3-[(3β)-cholest-5-en-3-ylamino]propyl}-6-(7-nitrobenzofurazan-4-ylamino)hexanamide
  参考文献：
  名称：

  Synthetic Mimics of Small Mammalian Cell Surface Receptors

  摘要：

  Receptors on the surface of mammalian cells promote the uptake of cell-impermeable ligands by receptor-mediated endocytosis. To mimic this process, we synthesized small molecules designed to project anti-dinitrophenyl antibody-binding motifs from the surface of living Jurkat lymphocytes. These synthetic receptors comprise N-alkyl derivatives of 3beta-cholesterylamine as the plasma membrane anchor linked to 2,4-dinitrophenyl (DNP) and structurally similar fluorescent 7-nitrobenz-2-oxa-1,3-diazole (NBD) headgroups. Insertion of two beta-alanine subunits between a DNP derivative and 3beta-cholesterylamine yielded a receptor that avidly associates with cell surfaces (cellular t(1/2) similar to 20 h). When added to Jurkat cells at 10 muM, this receptor enhanced uptake of an anti-DNP IgG ligand by similar to200-fold in magnitude and similar to400-fold in rate within 4 h (ligand internalization t(1/2) similar to 95 min at 37 degreesC). This non-natural receptor mimics many natural receptors by dynamically cycling between plasma membranes and intracellular endosomes (recycling t(1/2) similar to 3 min), targeting of protein ligands to proposed cholesterol and sphingolipid-enriched lipid raft membrane microdomains, and delivery of protein ligands to late endosomes/lysosomes. Quantitative dithionite quenching of fluorescent extracellular NBD headgroups demonstrated that other 3beta-cholesterylamine derivatives bearing fewer beta-alanines in the linker region or N-acyl derivatives of 3beta-cholesterylamine were less effective receptors due to more extensive trafficking to internal membranes. Synthetic cell surface receptors have potential applications as cellular probes, tools for drug delivery, and methods to deplete therapeutically important extracellular ligands.

  DOI：

  10.1021/ja046663o
• 作为产物：
  描述：

  N-cholesteryl-2-nitrobenzenesulfonamide 在 potassium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 29.0h， 生成 N-(3-{(3β)-cholest-5-en-3-yl[(2-nitrophenyl)sulfonyl]amino}propyl)-6-(7-nitrobenzofurazan-4-ylamino)hexanamide
  参考文献：
  名称：

  Synthetic Mimics of Small Mammalian Cell Surface Receptors

  摘要：

  Receptors on the surface of mammalian cells promote the uptake of cell-impermeable ligands by receptor-mediated endocytosis. To mimic this process, we synthesized small molecules designed to project anti-dinitrophenyl antibody-binding motifs from the surface of living Jurkat lymphocytes. These synthetic receptors comprise N-alkyl derivatives of 3beta-cholesterylamine as the plasma membrane anchor linked to 2,4-dinitrophenyl (DNP) and structurally similar fluorescent 7-nitrobenz-2-oxa-1,3-diazole (NBD) headgroups. Insertion of two beta-alanine subunits between a DNP derivative and 3beta-cholesterylamine yielded a receptor that avidly associates with cell surfaces (cellular t(1/2) similar to 20 h). When added to Jurkat cells at 10 muM, this receptor enhanced uptake of an anti-DNP IgG ligand by similar to200-fold in magnitude and similar to400-fold in rate within 4 h (ligand internalization t(1/2) similar to 95 min at 37 degreesC). This non-natural receptor mimics many natural receptors by dynamically cycling between plasma membranes and intracellular endosomes (recycling t(1/2) similar to 3 min), targeting of protein ligands to proposed cholesterol and sphingolipid-enriched lipid raft membrane microdomains, and delivery of protein ligands to late endosomes/lysosomes. Quantitative dithionite quenching of fluorescent extracellular NBD headgroups demonstrated that other 3beta-cholesterylamine derivatives bearing fewer beta-alanines in the linker region or N-acyl derivatives of 3beta-cholesterylamine were less effective receptors due to more extensive trafficking to internal membranes. Synthetic cell surface receptors have potential applications as cellular probes, tools for drug delivery, and methods to deplete therapeutically important extracellular ligands.

  DOI：

  10.1021/ja046663o

文献信息

• Synthetic mimics of mammalian cell surface receptors: method and compositions
  申请人：Peterson R. Blake

  公开号：US20060229235A1

  公开（公告）日：2006-10-12

  The present invention relates to new synthetic receptors. More particularly, the present invention relates to the use of the synthetic receptors for delivering a protein, peptide, drug, prodrug, lipid, nucleic acid, carbohydrate or small molecule into a target cell via receptor-mediated endocytosis. According to the invention, novel synthetic mimics of cell surface receptors have been designed and methods for use of the same are disclosed.

  本发明涉及新的合成受体。更具体地，本发明涉及利用合成受体通过受体介导的内吞作用将蛋白质、肽、药物、前药、脂质、核酸、碳水化合物或小分子输送到靶细胞中。根据本发明，已设计了细胞表面受体的新型合成模拟物，并公开了其使用方法。
• SYNTHETIC MIMICS OF MAMMALIAN CELL SURFACE RECEPTORS: METHOD AND COMPOSITIONS
  申请人：PETERSON BLAKE R.

  公开号：US20100160657A1

  公开（公告）日：2010-06-24

  The present invention relates to new synthetic receptors. More particularly, the present invention relates to methods for synthesizing preferred membrane-binding elements, preferably cholesterylamine derivatives, including 3β-amino-5-cholestene (3β-cholesterylamine) and related 3β-halides through i-steroid and retro-i-steroid rearrangements. The invention further relates to use of the synthetic receptors for delivering a protein, peptide, drug, prodrug, lipid, nucleic acid, carbohydrate or small molecule into a target cell via receptor-mediated endocytosis. According to the invention, novel synthetic mimics of cell surface receptors have been designed and methods for use of the same are disclosed.

  本发明涉及新的合成受体。更具体地说，本发明涉及用于合成首选膜结合元素（优选为胆固醇胺衍生物，包括3β-氨基-5-胆甾烷（3β-胆固醇胺）和相关的3β-卤化物）的方法，包括通过i-类固醇和retro-i-类固醇重排。本发明进一步涉及利用合成受体通过受体介导的内吞作用将蛋白质、肽、药物、前药、脂质、核酸、碳水化合物或小分子输送到靶细胞的用途。根据本发明，新的细胞表面受体合成类似物已被设计，并公开了使用这些类似物的方法。
• US7514400B2
  申请人：——

  公开号：US7514400B2

  公开（公告）日：2009-04-07
• US7956029B2
  申请人：——

  公开号：US7956029B2

  公开（公告）日：2011-06-07
• US7947647B2
  申请人：——

  公开号：US7947647B2

  公开（公告）日：2011-05-24