N-2-[2-(N,N-diisopropylamino-β-cyanoethoxyphosphinoxy)ethoxy]ethyl-4-methoxybenzamide | 1234703-46-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-2-[2-(N,N-diisopropylamino-β-cyanoethoxyphosphinoxy)ethoxy]ethyl-4-methoxybenzamide
• 英文别名: N-[2-[2-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxyethoxy]ethyl]-4-methoxybenzamide
• CAS: 1234703-46-8
• 化学式: C₂₁H₃₄N₃O₅P
• 分子量: 439.492
• InChiKey: GERHZRQRCKDIRH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  30
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  93
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-2-(2-hydroxyethoxy)ethyl-4-methoxybenzamide 、 2-氰乙基N,N-二异丙基氯亚磷酰胺 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以43%的产率得到N-2-[2-(N,N-diisopropylamino-β-cyanoethoxyphosphinoxy)ethoxy]ethyl-4-methoxybenzamide
  参考文献：
  名称：

  Targeted Intracellular Delivery of Antisense Oligonucleotides via Conjugation with Small-Molecule Ligands

  摘要：

  Selective delivery of antisense or siRNA oligonucleotides to cells and tissues via receptor-mediated endocytosis is becoming an important approach for oligonucleotide-based pharmacology. In most cases receptor targeting has been attained using antibodies or peptide-type ligands. Thus, there are few examples of delivering oligonucleotides using the plethora of small-molecule receptor-specific ligands that currently exist. In this report we describe a facile approach to the generation of mono- and multivalent conjugates of oligonucleotides with small-molecule ligands. Using the sigma-receptor ligand anisamide as an example, we describe conversion of the ligand to a phosphoramidite and direct incorporation of this moiety into the oligonucleotide by solid-phase DNA synthesis. We generated mono- and trivalent conjugates of anisamide with a splice switching antisense oligonucleotide (SSO) and tested their ability to modify splicing of a reporter gene (luciferase) in tumor cells in culture. The trivalent anisamide-SSO conjugate displayed enhanced cellular uptake and was markedly more effective than an unconjugated SSO or the monovalent conjugate in modifying splicing of the reporter. Significant biological effects were attained in the sub-100 nM concentration range.

  DOI：

  10.1021/ja102635c

文献信息

• [EN] TARGETED INTRACELLULAR DELIVERY OF OLIGONUCLEOTIDES VIA CONJUGATION WITH SMALL MOLECULE LIGANDS<br/>[FR] DÉLIVRANCE INTRACELLULAIRE CIBLÉE D'OLIGONUCLÉOTIDES PAR CONJUGAISON AVEC DE PETITES MOLÉCULES DE LIGANDS
  申请人：UNIV NORTH CAROLINA

  公开号：WO2011126937A1

  公开（公告）日：2011-10-13

  An oligonucleotide covalently coupled to at least one ligand for a membrane bound protein is provided. The ligand is preferably so coupled through a linking group. The linking group preferably comprising a phosphate group covalently coupled to a substituted or unsubstituted aliphatic group or a substituted or unsubstituted aliphatic oxide group. The compounds may be provided as salts, including pharmaceutically acceptable salts, thereof. Methods of making and using the same are also provided.