N-(5-((2-((2-(2-(2-aminoethoxy)ethoxy)ethyl)benzyl)amino)-1-hydroxyethyl)-2-(benzyloxy)phenyl)formamide trifluoroacetate | 1068147-92-1

• 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-(5-((2-((2-(2-(2-aminoethoxy)ethoxy)ethyl)benzyl)amino)-1-hydroxyethyl)-2-(benzyloxy)phenyl)formamide trifluoroacetate
• 英文别名: N-[5-[2-[2-[2-(2-aminoethoxy)ethoxy]ethyl-benzylamino]-1-hydroxyethyl]-2-phenylmethoxyphenyl]formamide;2,2,2-trifluoroacetic acid
• CAS: 1068147-92-1
• 化学式: C₂HF₃O₂*C₂₉H₃₇N₃O₅
• 分子量: 621.654
• InChiKey: MHHWJJWHELLGTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.99
• 重原子数：
  44
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  144
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  N-(5-((2-((2-(2-(2-aminoethoxy)ethoxy)ethyl)benzyl)amino)-1-hydroxyethyl)-2-(benzyloxy)phenyl)formamide trifluoroacetate 、 6-氯嘌呤核苷 在 N,N-二异丙基乙胺 作用下， 以 叔丁醇 为溶剂， 反应 24.0h， 以50%的产率得到N(5-(2-((2-(2-(N6-adenosinylethoxy)ethoxy)ethyl)(benzyl)amino)-1-hydroxyethyl)-2-(benzyloxy)phenyl)formamide
  参考文献：
  名称：

  Synthesis of Bivalent β₂-Adrenergic and Adenosine A₁ Receptor Ligands

  摘要：

  Research in the area of simutaneously targeting more than one G protein-coupled receptor (GPCR) has increased in recent times. By exploiting the cross talk between the beta(2)-adrenergic (beta(2)AR) and adenosine A(1) receptors (A(1)AR) on adenylate cyclase activity, we synthesized a series of bivalent agonists for both GPCRs to generate responses from more than one receptor. We have demonstrated a relationship between the various beta(2)-adrenergic and A(1) adenosine bivalent parameters of linker and bifunctionality by using data that are drawn from in vitro assays. The hexyl-linked 12e (K-i, 311 nM) and butyl-linked 12c (K-i, 863 nM) bivalent compounds displayed reasonable binding affinities for the PAR when compared with the control (-)isoproterenol (K-i, 136 nM), and both compounds also exhibited a persuasive bifunctional trend for both receptors at various drug concentrations. The bivalent compound 12e was also found to have significant EC50 potency (6 nM) at the beta(2)AR in DDT cells.

  DOI：

  10.1021/jm800613s
• 作为产物：
  描述：

  tert-butyl 2-(2-(2-(benzyl(2-(4-(benzyloxy)-3-formamidophenyl)hydroxyethyl)amino)ethoxy)ethoxy)ethylcarbamate 、 三氟乙酸 以 二氯甲烷 为溶剂， 以100%的产率得到N-(5-((2-((2-(2-(2-aminoethoxy)ethoxy)ethyl)benzyl)amino)-1-hydroxyethyl)-2-(benzyloxy)phenyl)formamide trifluoroacetate
  参考文献：
  名称：

  Synthesis of Bivalent β₂-Adrenergic and Adenosine A₁ Receptor Ligands

  摘要：

  Research in the area of simutaneously targeting more than one G protein-coupled receptor (GPCR) has increased in recent times. By exploiting the cross talk between the beta(2)-adrenergic (beta(2)AR) and adenosine A(1) receptors (A(1)AR) on adenylate cyclase activity, we synthesized a series of bivalent agonists for both GPCRs to generate responses from more than one receptor. We have demonstrated a relationship between the various beta(2)-adrenergic and A(1) adenosine bivalent parameters of linker and bifunctionality by using data that are drawn from in vitro assays. The hexyl-linked 12e (K-i, 311 nM) and butyl-linked 12c (K-i, 863 nM) bivalent compounds displayed reasonable binding affinities for the PAR when compared with the control (-)isoproterenol (K-i, 136 nM), and both compounds also exhibited a persuasive bifunctional trend for both receptors at various drug concentrations. The bivalent compound 12e was also found to have significant EC50 potency (6 nM) at the beta(2)AR in DDT cells.

  DOI：

  10.1021/jm800613s

文献信息

• Synthesis of Bivalent β₂-Adrenergic and Adenosine A₁ Receptor Ligands
  作者：Peter Karellas、Michael McNaughton、Stephen P. Baker、Peter J. Scammells

  DOI：10.1021/jm800613s

  日期：2008.10.9

  Research in the area of simutaneously targeting more than one G protein-coupled receptor (GPCR) has increased in recent times. By exploiting the cross talk between the beta(2)-adrenergic (beta(2)AR) and adenosine A(1) receptors (A(1)AR) on adenylate cyclase activity, we synthesized a series of bivalent agonists for both GPCRs to generate responses from more than one receptor. We have demonstrated a relationship between the various beta(2)-adrenergic and A(1) adenosine bivalent parameters of linker and bifunctionality by using data that are drawn from in vitro assays. The hexyl-linked 12e (K-i, 311 nM) and butyl-linked 12c (K-i, 863 nM) bivalent compounds displayed reasonable binding affinities for the PAR when compared with the control (-)isoproterenol (K-i, 136 nM), and both compounds also exhibited a persuasive bifunctional trend for both receptors at various drug concentrations. The bivalent compound 12e was also found to have significant EC50 potency (6 nM) at the beta(2)AR in DDT cells.