N⁶-(aminobutyl)adenosine | 60687-66-3

• 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-(aminobutyl)adenosine
• 英文别名: N⁶-(4-amino-butyl)-adenosine；(2R,3R,4S,5R)-2-[6-(4-aminobutylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 60687-66-3
• 化学式: C₁₄H₂₂N₆O₄
• 分子量: 338.366
• InChiKey: JZYJGLYAZHFZKM-IDTAVKCVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  152
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N⁶-(aminobutyl)adenosine 在 三乙胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 2',3'-O-<<methyl>ethoxymethylidene>-2'',3''-O-(methoxyethylidene)-1,4-di(adenosin-N6-yl)butane
  参考文献：
  名称：

  用2'（3'）-O-乙酰基2英寸（3英寸）-O-糖基-1,2-二（腺苷-N6-基）乙烷和-1,4-二（腺苷-）抑制核糖体肽基转移酶N6-基）丁烷。烷基链长的影响。

  摘要：

  DOI：

  10.1021/jm00181a015
• 作为产物：
  描述：

  2’,3’,5’-三乙酰肌苷 在 palladium on activated charcoal 氢气 、 溶剂黄146 、 N,N-二甲基苯胺 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 21.22h， 生成 N⁶-(aminobutyl)adenosine
  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 conjugates of mycophenolic acid and their antiproliferative activity
  作者：Michał Prejs、Grzegorz Cholewinski、Agnieszka Siebert、Piotr Trzonkowski、Krystyna Dzierzbicka

  DOI：10.1080/10286020.2016.1184653

  日期：2016.11.1

  The new conjugates of mycophenolic acid (MPA) were obtained in the reaction of N6-(ω-aminoalkyl)adenosines with MPA in the presence of EDCI as a coupling reagent. New compounds 4a–h were evaluated on leukemia cell line (Jurkat) and PBMC from healthy donors. Length of the linker influenced observed activity. The compound 4b possessing 1,3-diamine spacer exhibited the most promising results and can be

  在EDCI作为偶联剂的存在下，N 6-（ω-氨基烷基）腺苷与MPA的反应获得了新的霉酚酸（MPA）共轭物。在健康捐献者的白血病细胞系（Jurkat）和PBMC上评估了新化合物4a–h。接头的长度影响观察到的活性。具有1，3-二胺间隔基的化合物4b显示出最有希望的结果，可以考虑用于进一步的研究。
• Adenosine Analogues as Inhibitors of <i>Trypanosoma </i><i>b</i><i>rucei </i>Phosphoglycerate Kinase:  Elucidation of a Novel Binding Mode for a 2-Amino-N⁶-Substituted Adenosine
  作者：Jerome C. Bressi、Jungwoo Choe、Melinda T. Hough、Frederick S. Buckner、Wesley C. Van Voorhis、Christophe L. M. J. Verlinde、Wim G. J. Hol、Michael H. Gelb

  DOI：10.1021/jm000287a

  日期：2000.11.1

  As part of a project aimed at structure-based design of adenosine analogues as drugs against African trypanosomiasis, N-6-, 2-amino-N-6-, and N-2-substituted adenosine analogues were synthesized and tested to establish structure-activity relationships for inhibiting Trypanosoma brucei glycosomal phosphoglycerate kinase (PGK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and glycerol-3-phosphate dehydrogenase (GPDH). Evaluation of X-ray structures of parasite PGK, GAPDH, and GPDH complexed with their adenosyl-bearing substrates led us to generate a series of adenosine analogues which would target all three enzymes simultaneously. There was a modest preference by PGK for NG-substituted analogues bearing the 2-amino group. The best compound in this series, 2-amino-N-6-[2 "-(p-hydroxyphenyl)ethyl]adenosine (46b), displayed a 23-fold improvement over adenosine with an IC50 of 130 muM. 2-[[2 "-(p-Hydroxyphenyl)ethyl]amino]adenosine (46c) was a weak inhibitor of T. brucei PGK with an IC50 of 500 muM. To explore the potential of an additive effect that having the N-6 and N-2 substitutions in one molecule might provide, the best ligands from the two series were incorporated into N-6,N-2-disubstituted adenosine analogues to yield N-6-(2 " -phenylethyl)-2-[(2 " -phenylethyl)amino]adenosine (69) as a 30 muM inhibitor of T. brucei PGK which is 100-fold more potent than the adenosine template. In contrast, these series gave no compounds that inhibited parasitic GAPDH or GPDH more than 10-20% when tested at 1.0 mM. A 3.0 Angstrom X-ray structure of a T, brucei PGK/46b complex revealed a binding mode in which the nucleoside analogue was flipped and the ribosyl moiety adopted a syn conformation as compared with the previously determined binding mode of ADP. Molecular docking experiments using QXP and SAS program suites reproduced this "flipped and rotated" binding mode.
• Inhibition of ribosomal peptidyltransferase with 2'(3')-O-acetyl-2"(3")-O-glycyl-1,2-di(adenosin-N6-yl)ethane and -1,4-di(adenosin-N6-yl)butane. Effect of alkyl chain length
  作者：Masayoshi Murata、Prakash Bhuta、James Owens、Jiri Zemlicka

  DOI：10.1021/jm00181a015

  日期：1980.7
• 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.