N⁶-(4-aminobutyl)-5'-ethylamino-5'-oxo-5'-deoxyadenosine | 773072-13-2

• 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-aminobutyl)-5'-ethylamino-5'-oxo-5'-deoxyadenosine
• 英文别名: N6-(4-Aminobutyl)-5'-ethylamino-5'-oxo-5'-deoxyadenosine；(2S,3S,4R,5R)-5-[6-(4-aminobutylamino)purin-9-yl]-N-ethyl-3,4-dihydroxyoxolane-2-carboxamide
• CAS: 773072-13-2
• 化学式: C₁₆H₂₅N₇O₄
• 分子量: 379.419
• InChiKey: JNYURUZWKMUUJD-MEQWQQMJSA-N

物化性质

• 密度：
  1.62±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  160
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N⁶-(4-aminobutyl)-5'-ethylamino-5'-oxo-5'-deoxyadenosine 、 N-dansyl-8-aminooctanoic acid 在 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 ABEA-AO-dansyl
  参考文献：
  名称：

  Influence of fluorophore and linker composition on the pharmacology of fluorescent adenosine A1 receptor ligands

  摘要：

  Background and purpose:  The introduction of fluorescence‐based techniques, and in particular the development of fluorescent ligands, has allowed the study of G protein‐coupled receptor pharmacology at the single cell and single molecule level. This study evaluated how the physicochemical nature of the linker and the fluorophore affected the pharmacological properties of fluorescent agonists and antagonists.Experimental approach:  Chinese hamster ovary cells stably expressing the human adenosine A1 receptor and a cyclic 3′,5′ adenosine monophosphate response element‐secreted placental alkaline phosphatase (CRE‐SPAP) reporter gene, together with whole cell [3H]‐8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX) radioligand binding, were used to evaluate the pharmacological properties of a range of fluorescent ligands based on the antagonist xanthine amine congener (XAC) and the agonist 5′ (N‐ethylcarboxamido) adenosine (NECA).Key results:  Derivatives of NECA and XAC with different fluorophores, but equivalent linker length, showed significant differences in their binding properties to the adenosine A1 receptor. The BODIPY 630/650 derivatives had the highest affinity. Linker length also affected the pharmacological properties, depending on the fluorophore used. Particularly in fluorescent agonists, higher agonist potency could be achieved with large or small linkers for dansyl and BODIPY 630/650 derivatives, respectively.Conclusions and implications:  The pharmacology of a fluorescent ligand was critically influenced by both the fluorophore and the associated linker. Furthermore, our data strongly suggest that the physicochemical properties of the fluorophore/linker pairing determine where in the environment of the target receptor the fluorophore is placed, and this, together with the environmental sensitivity of the resulting fluorescence, may finally decide its utility as a fluorescent probe.This article is part of a themed section on Imaging in Pharmacology. To view the editorial for this themed section visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00685.x

  DOI：

  10.1111/j.1476-5381.2009.00488.x
• 作为产物：
  描述：

  2',3'-O-异丙叉肌苷 在 palladium on activated charcoal 盐酸 、 氯化亚砜 、 2,2,6,6-四甲基哌啶氧化物 、 碘苯二乙酸 、 氢气 、 溶剂黄146 、 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 、 甲醇 、 乙醇 、 氯仿 、 水 、 乙腈 为溶剂， 反应 30.5h， 生成 N⁶-(4-aminobutyl)-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

• 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。
• FLUORESCENTLY TAGGED LIGANDS
  申请人：The University of Nottingham

  公开号：EP1623223A2

  公开（公告）日：2006-02-08
• [EN] FLUORESCENTLY TAGGED LIGANDS<br/>[FR] LIGANDS MARQUÉS PAR FLUORESCENCE
  申请人：UNIV NOTTINGHAM

  公开号：WO2004088312A2

  公开（公告）日：2004-10-14

  Library comprising a plurality of tagged non-peptide ligands of formula (I): (Lig JL)m L(JT Tag) m (JTL(JLLig)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 JT and JL 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, CI-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, JL, L JT and/or - Tag and is at different linking sites in compounds comprising same Lig, JL, L JT 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.
• 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.
• Influence of fluorophore and linker composition on the pharmacology of fluorescent adenosine A1 receptor ligands
  作者：Jillian G Baker、Richard Middleton、Luke Adams、Lauren T May、Stephen J Briddon、Barrie Kellam、Stephen J Hill

  DOI：10.1111/j.1476-5381.2009.00488.x

  日期：2010.2

  Background and purpose:  The introduction of fluorescence‐based techniques, and in particular the development of fluorescent ligands, has allowed the study of G protein‐coupled receptor pharmacology at the single cell and single molecule level. This study evaluated how the physicochemical nature of the linker and the fluorophore affected the pharmacological properties of fluorescent agonists and antagonists.Experimental approach:  Chinese hamster ovary cells stably expressing the human adenosine A1 receptor and a cyclic 3′,5′ adenosine monophosphate response element‐secreted placental alkaline phosphatase (CRE‐SPAP) reporter gene, together with whole cell [3H]‐8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX) radioligand binding, were used to evaluate the pharmacological properties of a range of fluorescent ligands based on the antagonist xanthine amine congener (XAC) and the agonist 5′ (N‐ethylcarboxamido) adenosine (NECA).Key results:  Derivatives of NECA and XAC with different fluorophores, but equivalent linker length, showed significant differences in their binding properties to the adenosine A1 receptor. The BODIPY 630/650 derivatives had the highest affinity. Linker length also affected the pharmacological properties, depending on the fluorophore used. Particularly in fluorescent agonists, higher agonist potency could be achieved with large or small linkers for dansyl and BODIPY 630/650 derivatives, respectively.Conclusions and implications:  The pharmacology of a fluorescent ligand was critically influenced by both the fluorophore and the associated linker. Furthermore, our data strongly suggest that the physicochemical properties of the fluorophore/linker pairing determine where in the environment of the target receptor the fluorophore is placed, and this, together with the environmental sensitivity of the resulting fluorescence, may finally decide its utility as a fluorescent probe.This article is part of a themed section on Imaging in Pharmacology. To view the editorial for this themed section visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00685.x