2-(n-butylamino)adenosine | 255716-02-0

• 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: 2-(n-butylamino)adenosine
• 英文别名: (2R,3R,4S,5R)-2-[6-amino-2-(butylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 255716-02-0
• 化学式: C₁₄H₂₂N₆O₄
• 分子量: 338.366
• InChiKey: LJWLPFCQLKDNTR-QYVSTXNMSA-N

物化性质

• 沸点：
  699.6±65.0 °C(Predicted)
• 密度：
  1.72±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  24
• 可旋转键数：
  6
• 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：

  2-(n-butylamino)adenosine 在 Proton Sponge 、 三氯氧磷 作用下， 以 various solvent(s) 为溶剂， 反应 2.33h， 生成
  参考文献：
  名称：

  P2Y（1）受体修饰的腺嘌呤核苷酸的分子识别。1.一种合成，生化和NMR方法。

  摘要：

  关于火鸡红细胞膜中P2Y（1）-受体（P2Y（1）-R）活化的2-硫醚-腺嘌呤核苷酸的显着高效能代表了某些替代天然物质所促进的最大效能提升受体配体。本文介绍了有关这些P2Y（1）-R配体比ATP高效力的起源的研究。在这项研究中，采用了一种综合方法，将新的ATP类似物的合成，其生化评估以及涉及NMR实验和理论计算的SAR分析相结合。进行这些实验和计算以阐明其构象并评估所研究的P2Y（1）-R配体的电子性质。合成的ATP类似物包括衍生物，其中C2或C8位置被供电子基团（例如醚，硫醚或胺）取代。测试了化合物在火鸡红细胞中诱导P2Y（1）-R介导的磷脂酶C活化和大鼠星形胶质细胞Ca（2+）反应的效力。8-取代的ATP和AMP衍生物对磷脂酶C或钙水平几乎没有或没有影响，而相应的2-取代的ATP类似物有效地增加了肌醇磷酸酯和Ca（2 +）（i）的水平。除2-丁基硫代-AMP引起小的Ca（2+）反应外，

  DOI：

  10.1021/jm990156d
• 作为产物：
  描述：

  6-氯鸟嘌呤核苷 在 copper(l) iodide 、 氨 、 碘 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 乙二醇甲醚 为溶剂， 反应 42.5h， 生成 2-(n-butylamino)adenosine
  参考文献：
  名称：

  Adenosine Analogues as Inhibitors of Trypanosoma brucei Phosphoglycerate Kinase:  Elucidation of a Novel Binding Mode for a 2-Amino-N⁶-Substituted Adenosine

  摘要：

  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.

  DOI：

  10.1021/jm000287a

文献信息

• 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.
• Molecular Recognition of Modified Adenine Nucleotides by the P2Y₁-Receptor. 1. A Synthetic, Biochemical, and NMR Approach
  作者：Efrat Halbfinger、Dan T. Major、Marco Ritzmann、Joachim Ubl、Georg Reiser、Jose L. Boyer、Kendall T. Harden、Bilha Fischer

  DOI：10.1021/jm990156d

  日期：1999.12.1

  evaluation, and their SAR analysis involving NMR experiments and theoretical calculations. These experiments and calculations were performed to elucidate the conformation and to evaluate the electronic nature of the investigated P2Y(1)-R ligands. ATP analogues synthesized included derivatives where C2 or C8 positions were substituted with electron-donating groups such as ethers, thioethers, or amines

  关于火鸡红细胞膜中P2Y（1）-受体（P2Y（1）-R）活化的2-硫醚-腺嘌呤核苷酸的显着高效能代表了某些替代天然物质所促进的最大效能提升受体配体。本文介绍了有关这些P2Y（1）-R配体比ATP高效力的起源的研究。在这项研究中，采用了一种综合方法，将新的ATP类似物的合成，其生化评估以及涉及NMR实验和理论计算的SAR分析相结合。进行这些实验和计算以阐明其构象并评估所研究的P2Y（1）-R配体的电子性质。合成的ATP类似物包括衍生物，其中C2或C8位置被供电子基团（例如醚，硫醚或胺）取代。测试了化合物在火鸡红细胞中诱导P2Y（1）-R介导的磷脂酶C活化和大鼠星形胶质细胞Ca（2+）反应的效力。8-取代的ATP和AMP衍生物对磷脂酶C或钙水平几乎没有或没有影响，而相应的2-取代的ATP类似物有效地增加了肌醇磷酸酯和Ca（2 +）（i）的水平。除2-丁基硫代-AMP引起小的Ca（2+）反应外，