N⁶-(4-benzyloxycarbonylaminobutyl)-5'-ethylamino-5'-oxo-5'-deoxyadenosine | 773072-12-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: N⁶-(4-benzyloxycarbonylaminobutyl)-5'-ethylamino-5'-oxo-5'-deoxyadenosine
• 英文别名: N6-(4-Benzyloxycarbonylaminobutyl)-5'-ethylamino-5'-oxo-5'-deoxyadenosine；benzyl N-[4-[[9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxyoxolan-2-yl]purin-6-yl]amino]butyl]carbamate
• CAS: 773072-12-1
• 化学式: C₂₄H₃₁N₇O₆
• 分子量: 513.553
• InChiKey: GTUHVBPTNXVWTQ-QPXQOZNCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  173
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N⁶-(4-benzyloxycarbonylaminobutyl)-5'-ethylamino-5'-oxo-5'-deoxyadenosine 在 钯 氢气 、 甲醇 、 乙腈 作用下， 以 Acetic acid methanol water 为溶剂， 反应 3.0h， 以to give the title compound 6 (35 mg, quant.) as a colourless oil的产率得到N⁶-(4-aminobutyl)-5'-ethylamino-5'-oxo-5'-deoxyadenosine
  参考文献：
  名称：

  Fluorescently tagged ligands

  摘要：

  该文描述了一个包含多种标记非肽配体的图书馆，其中配体的化学式为I（LigJL）mL（JTTag）m（JTL（JLLig）m）p，包括其盐。该图书馆包括一个或多个相同或不同的配体基团Lig，每个基团与一个或多个相同或不同的标记基团Tag通过相同或不同的连接基团L和相同或不同的连接位点或连接功能JT和JL相连。其中，Lig包括GPCR配体、细胞内酶的抑制剂或药物转运体的底物或抑制剂；L是单键或任何连接基团，选自异原子如N、O、S、P、支链或直链饱和或不饱和、可选含有杂原子的C1-600烃基和这些基团的组合，可以是单体、寡聚物，其寡聚重复次数为2到30，或聚合物，其聚合重复次数超过30到300；Tag是任何已知或新颖的标记底物；m是独立选择的整数，范围从1到3；p是0到3。该文还描述了在不同的连接位点连接不同的Lig、JL、L、JT和/或-Tag的化合物中，连接在相同的连接位点，而在包含相同Lig、JL、L、JT和/或-Tag的化合物中，连接在不同的连接位点。该文还描述了制备该图书馆化合物的过程，制备化合物I的前体化合物IV的过程，从图书馆中选择化合物I的方法，与其相关的药理特性信息的化合物I，新颖的化合物I或前体化合物IV，以及它们的用途，与之结合或抑制的方法，与荧光靶标一起使用的方法，修改的细胞表面GPCR和表达相同的细胞，以及包括化合物I和其靶标的试剂盒。

  公开号：

  US20060211045A1
• 作为产物：
  描述：

  2',3'-O-异丙叉肌苷 在 盐酸 、 氯化亚砜 、 2,2,6,6-四甲基哌啶氧化物 、 碘苯二乙酸 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 氯仿 、 水 、 乙腈 为溶剂， 反应 30.5h， 生成 N⁶-(4-benzyloxycarbonylaminobutyl)-5'-ethylamino-5'-oxo-5'-deoxyadenosine
  参考文献：
  名称：

  New Fluorescent Adenosine A₁-Receptor Agonists That Allow Quantification of Ligand−Receptor Interactions in Microdomains of Single Living Cells

  摘要：

  Fluorescence spectroscopy is becoming a valuable addition to the array of techniques available for scrutinizing ligand-receptor interactions in biological systems. In particular, scanning confocal microscopy and fluorescence correlation spectroscopy (FCS) allow the noninvasive imaging and quantification of these interactions in single living cells. To address the emerging need for fluorescently labeled ligands to support these technologies, we have developed a series of red-emitting agonists for the human adenosine A(1)-receptor that, collectively, are N-6-aminoalkyl derivatives of adenosine or adenosine 5'-N-ethyl carboxamide. The agonists, which incorporate the commercially available fluorophore BODIPY [630/650], retain potent and efficacious agonist activity, as demonstrated by their ability to inhibit cAMP accumulation in chinese hamster ovary cells expressing the human adenosine A(1)-receptor. Visualization and confirmation of ligand-receptor interactions at the cell membrane were accomplished using confocal microscopy, and their suitability for use in FCS was demonstrated by quantification of agonist binding in small areas of cell membrane.

  DOI：

  10.1021/jm061279i

文献信息

• New Fluorescent Adenosine A₁-Receptor Agonists That Allow Quantification of Ligand−Receptor Interactions in Microdomains of Single Living Cells
  作者：Richard J. Middleton、Stephen J. Briddon、Yolande Cordeaux、Andrew S. Yates、Clare L. Dale、Michael W. George、Jillian. G. Baker、Stephen J. Hill、Barrie Kellam

  DOI：10.1021/jm061279i

  日期：2007.2.1

  Fluorescence spectroscopy is becoming a valuable addition to the array of techniques available for scrutinizing ligand-receptor interactions in biological systems. In particular, scanning confocal microscopy and fluorescence correlation spectroscopy (FCS) allow the noninvasive imaging and quantification of these interactions in single living cells. To address the emerging need for fluorescently labeled ligands to support these technologies, we have developed a series of red-emitting agonists for the human adenosine A(1)-receptor that, collectively, are N-6-aminoalkyl derivatives of adenosine or adenosine 5'-N-ethyl carboxamide. The agonists, which incorporate the commercially available fluorophore BODIPY [630/650], retain potent and efficacious agonist activity, as demonstrated by their ability to inhibit cAMP accumulation in chinese hamster ovary cells expressing the human adenosine A(1)-receptor. Visualization and confirmation of ligand-receptor interactions at the cell membrane were accomplished using confocal microscopy, and their suitability for use in FCS was demonstrated by quantification of agonist binding in small areas of cell membrane.
• Fluorescently tagged ligands
  申请人：George Michael

  公开号：US20060211045A1

  公开（公告）日：2006-09-21

  Library comprising a plurality of tagged non-peptide ligands of formula I (LigJ L ) m L(J T Tag) m (J T L(J L Lig) m ) p including and salts thereof comprising one or a plurality of same or different ligand moieties Lig each linked to a one or a plurality of same or different tag moieties Tag via same or different linker moieties L and same or different linking site or linking functionality J T and J L wherein Lig comprises a GPCR ligand, an inhibitor of an intracellular enzyme or a substrate or inhibitor of a drug transporter; L is a single bond or is any linking moiety selected from a heteroatom such as N, O, S, P, branched or straight chain saturated or unsaturated, optionally heteroatom containing, C 1-600 hydrocarbyl and combinations thereof, which may be monomeric, oligomeric having oligomeric repeat of 2 to 30 or polymeric having polymeric repeat in excess of 30 up to 300; Tag is any known or novel tagging substrate; m are each independently selected from a whole number integer from 1 to 3; p is 0 to 3 characterised in that linking is at same or different linking sites in compounds comprising different Lig, J L , L J T and/or -Tag and is at different linking sites in compounds comprising same Lig, J L , L J T and/or -Tag; process for the preparation thereof; process for the preparation of a library compound of formula I or a precursor of formula IV; method for selecting a compound of formula I from a library thereof; compound of formula I associated with information relating to its pharmacological properties; a novel compound of formula I or precursor of formula IV; uses thereof; methods for binding or inhibition therewith; use of a fluorescent target therewith; a modified cell surface GPCR and cells expressing the same; and a kit comprising a compound of formula I and a target therefor.

  该文描述了一个包含多种标记非肽配体的图书馆，其中配体的化学式为I（LigJL）mL（JTTag）m（JTL（JLLig）m）p，包括其盐。该图书馆包括一个或多个相同或不同的配体基团Lig，每个基团与一个或多个相同或不同的标记基团Tag通过相同或不同的连接基团L和相同或不同的连接位点或连接功能JT和JL相连。其中，Lig包括GPCR配体、细胞内酶的抑制剂或药物转运体的底物或抑制剂；L是单键或任何连接基团，选自异原子如N、O、S、P、支链或直链饱和或不饱和、可选含有杂原子的C1-600烃基和这些基团的组合，可以是单体、寡聚物，其寡聚重复次数为2到30，或聚合物，其聚合重复次数超过30到300；Tag是任何已知或新颖的标记底物；m是独立选择的整数，范围从1到3；p是0到3。该文还描述了在不同的连接位点连接不同的Lig、JL、L、JT和/或-Tag的化合物中，连接在相同的连接位点，而在包含相同Lig、JL、L、JT和/或-Tag的化合物中，连接在不同的连接位点。该文还描述了制备该图书馆化合物的过程，制备化合物I的前体化合物IV的过程，从图书馆中选择化合物I的方法，与其相关的药理特性信息的化合物I，新颖的化合物I或前体化合物IV，以及它们的用途，与之结合或抑制的方法，与荧光靶标一起使用的方法，修改的细胞表面GPCR和表达相同的细胞，以及包括化合物I和其靶标的试剂盒。