N6-(3-苯基丙基)腺苷 | 101565-57-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: N6-(3-苯基丙基)腺苷
• 英文名称: N⁶-(3-phenylpropan-1-yl)adenosine
• 英文别名: N6-(3-Phenylpropyl)adenosine；N-(3-Phenylpropyl)adenosine；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-(3-phenylpropylamino)purin-9-yl]oxolane-3,4-diol
• CAS: 101565-57-5
• 化学式: C₁₉H₂₃N₅O₄
• 分子量: 385.423
• InChiKey: UBRRRMDHTZACMR-NVQRDWNXSA-N

物化性质

• 沸点：
  721.3±70.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N6-(3-苯基丙基)腺苷 在 盐酸 作用下， 以 水 为溶剂， 反应 2.0h， 以84%的产率得到N⁶-(3-phenylpropyl)adenine
  参考文献：
  名称：

  从核苷化学酶促合成细胞分裂素：核糖作为封闭基团†

  摘要：

  核苷磷酸化酶参与核苷生物合成的挽救途径，并催化核碱基与α - D-核糖-1-磷酸的可逆反应，生成相应的核苷和无机磷酸盐。这些反应的平衡向核苷转移，特别是在嘌呤的情况下。嘌呤核苷磷酸化酶（PNP，EC 2.4.2.1）在实验室和工业中广泛用于合成具有实际重要性的核苷。细菌PNP利用相对广泛的具有不同取代基的嘌呤形成相应的核苷，具有相对较宽的底物特异性。为了使反应朝相反的方向进行，我们使用了砷解作用而不是磷解作用。由于生成的α-的水解，该反应是不可逆的D-核糖-1-砷。结果，杂环碱以定量产率形成并且可以容易地分离。我们已经开发出一种新的细胞分裂素制备方法，该方法基于在PNP和Na 2 HAsO 4存在下酶解N 6取代的腺苷的N-糖苷键的方法。根据HPLC分析，转化以定量产率进行。在提出的策略中，核糖残基充当保护基。最终产品具有的ASO无污染4 3-已经检测到通过HPLC-HRMS; 已经提出了通过ESI-MS进行简单的砷分析检测。

  DOI：

  10.1039/c8ob00223a
• 作为产物：
  描述：

  [(2R,3R,4R,5R)-3,4-diacetyloxy-5-[6-(3-phenylpropylamino)purin-9-yl]oxolan-2-yl]methyl acetate 在 正丙胺 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以208 mg的产率得到N6-(3-苯基丙基)腺苷
  参考文献：
  名称：

  N 6-苄基腺苷连接子的长度和结构的改变调节其针对肠道病毒的选择性抗病毒活性71

  摘要：

  最近，我们证明了N 6-异戊烯基腺苷，一种细胞分裂素核苷，对人肠病毒71的复制具有有效的选择性抗病毒作用。本研究致力于另一种天然化合物N 6-苄基腺苷的结构优化。我们主要研究腺嘌呤和苯环之间连接基的大小和性质，以及D-核糖残基的必要性。制备了30多种N 6-苄基腺苷类似物，并评估了它们的抗病毒特性。两种主要的制备方法：N 6-乙酰基-2'，3'，5'-tri- O-乙酰基腺苷可以在碱促进条件下通过烷基卤或在Mitsunobu反应中通过醇进行区域选择性烷基化。在室温下用4 M PrNH 2在MeOH中的溶液脱酰1天后，以高总收率获得所需产物。对结构-活性关系的分析清楚地表明，连接子的最佳尺寸限于2或3个原子（化合物4 – 7）。2'-脱氧腺苷衍生物没有引起任何抑制或细胞毒性作用，而5'-脱氧核苷仍然诱导了某些细胞保护性抗病毒活性。基于这些观察，可以假设除了可能的5'-三磷酸化继之以对RNA合

  DOI：

  10.1016/j.ejmech.2016.01.036

文献信息

• Anti-HCV nucleoside derivatives
  申请人：——

  公开号：US20030008841A1

  公开（公告）日：2003-01-09

  The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.

  本发明涉及新颖和已知的嘌呤和嘧啶核苷衍生物，已发现这些衍生物对丙型肝炎病毒（HCV）具有活性。本发明声明利用这些衍生物治疗HCV感染，以及本文所披露的新颖核苷衍生物。
• Comparative Study of Adenosine Analogs as Inhibitors of Protein Arginine Methyltransferases and a <i>Clostridioides difficile-</i>Specific DNA Adenine Methyltransferase
  作者：Jujun Zhou、Youchao Deng、Iredia D. Iyamu、John R. Horton、Dan Yu、Taraneh Hajian、Masoud Vedadi、Dante Rotili、Antonello Mai、Robert M. Blumenthal、Xing Zhang、Rong Huang、Xiaodong Cheng

  DOI：10.1021/acschembio.3c00035

  日期：——

  tools for studying and therapeutically inhibiting SAM-dependent methyltransferases (MTases). Some MTases play significant roles in host–pathogen interactions, one of which is Clostridioides difficile-specific DNA adenine MTase (CamA). CamA is needed for efficient sporulation and alters persistence in the colon. To discover potent and selective CamA inhibitors, we explored modifications of the solvent-exposed

  S-腺苷-l-甲硫氨酸 (SAM) 类似物是研究和治疗性抑制 SAM 依赖性甲基转移酶 (MTase) 的适应性工具。一些 MTase 在宿主-病原体相互作用中发挥重要作用，其中之一是艰难梭菌特异性DNA 腺嘌呤 MTase (CAMA)。CAMA 是有效孢子形成所必需的，并改变结肠中的持久性。为了发现有效且选择性的 CAMA 抑制剂，我们探索了 SAM 腺苷部分暴露于溶剂的边缘的修饰。从两个母体化合物（6e和7）开始，我们设计了一种腺苷类似物（11a），其在腺嘌呤N6-氨基上带有3-苯基丙基部分，在硫原子上带有3-（环己基甲基胍）-乙基部分核糖环。化合物11a (IC 50 = 0.15 μM) 的抗 CAMA 功效分别比6e和7强 10 倍和 5 倍。CAMA-DNA-抑制剂复合物的结构表明，11a采用U形构象，两个分支相互折叠，两端的脂肪环和芳香环相互作用。11a占据了腺苷结合位点旁边的整个疏水表面（显然是
• Dog coronary artery adenosine receptor. Structure of the N6-aryl subregion
  作者：Shozo Kusachi、Robert D. Thompson、Noboyuki Yamada、Daniel T. Daly、R. A. Olsson

  DOI：10.1021/jm00156a016

  日期：1986.6

  Previous structure-coronary vasoactivity correlations of the N6-alkyladenosine analogues of N6-[(R)-1-phenyl-2-propyl]adenosine, 1, support the hypothesis that the coronary artery A2 adenosine receptor contains an N6 region of specialized structure. The part of this receptor region that binds the 2-propyl moiety of 1 determines stereoselectivity and contributes to coronary vasoactivity. The present study uses 92 adenosine analogues containing an aryl group in the N6 substituent to test the hypothesis that the N6 receptor region contains an aryl subregion that binds the phenyl moiety of 1 and thereby contributes to its coronary vasoactivity. N6-Aralkyladenosines are often more potent than their alkyl congeners. Two methylene residues seem to provide optimum separation of the aryl group from N6. Among adenosines with semirigid N6 substituents, N6-[(1R,2S)-trans-2-phenylcyclohexyl]adenosine was uniquely active, evidence that when 1 occupies the receptor, the axis of the propyl C-1 to phenyl C-1 bond is nearly in the plane described by N6 and propyl C-1 and C-2. The torsion angle around this bond is unknown. Replacing the phenyl group of N6-2-phenethyladenosine with a thienyl or a 3-pyridyl group raises activity. The structure-activity relationships of the N6-(arylethyl)-, the N6-(arylmethyl)-, and the N6-phenyladenosines differ strinkingly from each other. Taken together, such results support the idea that the N6 region of the dog coronary artery A2 adenosine receptor includes an aryl subregion.
• 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.
• Nishikawa, Shiro; Kumazawa, Zenzaburo; Kashimura, Naoki, Agricultural and Biological Chemistry, 1986, vol. 50, # 9, p. 2243 - 2250
  作者：Nishikawa, Shiro、Kumazawa, Zenzaburo、Kashimura, Naoki、Nishimiki, Yoshio、Uemura, Shoji

  DOI：——

  日期：——