2-(4-phenyl-1-butyn-1-yl)adenosine | 141345-16-6

• 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-(4-phenyl-1-butyn-1-yl)adenosine
• 英文别名: (2R,3R,4S,5R)-2-[6-amino-2-(4-phenylbut-1-ynyl)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 141345-16-6
• 化学式: C₂₀H₂₁N₅O₄
• 分子量: 395.418
• InChiKey: DMSPOLNMPCSGKG-AEVYOOLXSA-N

物化性质

• 沸点：
  777.0±70.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(4-phenyl-1-butyn-1-yl)adenosine 在 10 percent Pd/C 吡啶 、 N-甲基咪唑 、 2,3,5-三甲基吡啶 、 三甲基氯硅烷 、 18-冠醚-6 、 氢气 、 potassium hydride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 4.33h， 生成 5'-O-(4,4'-dimethoxytrityl)-2'-O-(tert-butyldimethylsilyl)-N⁶-benzoyl-2-(4-phenylbutyl)adenosine 3'-N,N-disopropyl(cyanoethyl)phosphoramidite
  参考文献：
  名称：

  Design of an Adenosine Analogue that Selectively Improves the Affinity of a Mutant U1A Protein for RNA

  摘要：

  The RNA recognition motif (RRM), one of the most common RNA binding domains, contains three highly conserved aromatic amino acids that participate in stacking interactions with RNA bases. We have investigated the contribution of these highly conserved aromatic amino acids to the affinity of the complex formed between the N-terminal RRM of the U1A protein and stem loop 2 of U1 snRNA. Previously, we found that substitution of one of these conserved aromatic amino acids, Phe56, with Ala resulted in a large destabilization of the complex. Here, we have modified A6, the base in stem loop 2 RNA that stacks with Phe56, to compensate for a portion of the destabilization caused by the Phe56Ala mutation. We have designed two modified adenosines, A-3CPh and A-4CPh, in which a phenyl group is linked to the adenosine such that it may replace the phenyl group that is eliminated by the Phe56Ala mutation in the complex. We have found that incorporation of A-3CPh into stem loop 2 RNA stabilizes the complex formed with Phe56Ala by 0.6 kcal/mol, while incorporation of A-4CPh into stem loop 2 RNA stabilizes this complex by 1.8 kcal/mol. Either base modification destabilizes the wild-type complex by 0.8-0.9 kcal/mol. Experiments with other U1 A mutant proteins suggest that the stabilization of the complex between the Phe56Ala U1 A protein and stem loop 2 RNA is due to a specific interaction between the Phe56Ala U1A protein and A6-4CPh stem loop 2 RNA.

  DOI：

  10.1021/ja021267w
• 作为产物：
  描述：

  4-苯基-1-丁炔 、 2-碘腺苷 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以61%的产率得到2-(4-phenyl-1-butyn-1-yl)adenosine
  参考文献：
  名称：

  Nucleosides and nucleotides. 107. 2-(Cycloalkylalkynyl)adenosines: adenosine A2 receptor agonists with potent antihypertensive effects

  摘要：

  Adenosine receptor-binding profiles in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR) of a series of 2-(cycloalkylalkynyl)adenosines (2-CAAs) and their congeners are described. The structure-activity relationship of this series of compounds is discussed, focusing on the length of the alkynyl side chain and bulkiness of the terminal cycloalkyl substituents in terms of binding activity and cardiovascular effects. All the 2-CAAs had a preferential affinity for A2 receptors. Of these derivatives, 2-(3-cyclopentyl-1-propyn-1-yl)adenosine (10b) exhibited the most selective affinity for A2 receptors (K(i) ratio: A1/A2 = 70) on the basis of receptor binding. In the C-2 binding region of adenosine, compounds often have potent and/or selective A2 activity from introduction of an acetylenic group at the C-2 position followed by one methylene residue further followed by a hydrophobic substituent such as a cycloalkyl ring at the terminal position of the alkynyl side chain. Intravenous injection of 10b up to 100-mu-g/kg had a potent hypotensive effect without a marked decrease in heart rate in anesthetized SHR. Compounds 10j-s, with a hydroxyl group in the C-3" position of the alkynyl side chain, had a potent affinity for both A1 and A2 receptors, but they were not highly selective for A2 receptors. These compounds caused a marked bradycardia upon intravenous administration in anesthetized SHR. Oral administration of 10b (0.1-1 mg/kg) had a potent and long-lasting antihypertensive effect in conscious SHR.

  DOI：

  10.1021/jm00090a017

文献信息

• Nucleosides and nucleotides. 107. 2-(Cycloalkylalkynyl)adenosines: adenosine A2 receptor agonists with potent antihypertensive effects
  作者：Toichi Abiru、Takanori Miyashita、Yohko Watanabe、Toyofumi Yamaguchi、Haruhiko Machida、Akira Matsuda

  DOI：10.1021/jm00090a017

  日期：1992.6

  Adenosine receptor-binding profiles in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR) of a series of 2-(cycloalkylalkynyl)adenosines (2-CAAs) and their congeners are described. The structure-activity relationship of this series of compounds is discussed, focusing on the length of the alkynyl side chain and bulkiness of the terminal cycloalkyl substituents in terms of binding activity and cardiovascular effects. All the 2-CAAs had a preferential affinity for A2 receptors. Of these derivatives, 2-(3-cyclopentyl-1-propyn-1-yl)adenosine (10b) exhibited the most selective affinity for A2 receptors (K(i) ratio: A1/A2 = 70) on the basis of receptor binding. In the C-2 binding region of adenosine, compounds often have potent and/or selective A2 activity from introduction of an acetylenic group at the C-2 position followed by one methylene residue further followed by a hydrophobic substituent such as a cycloalkyl ring at the terminal position of the alkynyl side chain. Intravenous injection of 10b up to 100-mu-g/kg had a potent hypotensive effect without a marked decrease in heart rate in anesthetized SHR. Compounds 10j-s, with a hydroxyl group in the C-3" position of the alkynyl side chain, had a potent affinity for both A1 and A2 receptors, but they were not highly selective for A2 receptors. These compounds caused a marked bradycardia upon intravenous administration in anesthetized SHR. Oral administration of 10b (0.1-1 mg/kg) had a potent and long-lasting antihypertensive effect in conscious SHR.
• Design of an Adenosine Analogue that Selectively Improves the Affinity of a Mutant U1A Protein for RNA
  作者：Ying Zhao、Anne M. Baranger

  DOI：10.1021/ja021267w

  日期：2003.3.1

  The RNA recognition motif (RRM), one of the most common RNA binding domains, contains three highly conserved aromatic amino acids that participate in stacking interactions with RNA bases. We have investigated the contribution of these highly conserved aromatic amino acids to the affinity of the complex formed between the N-terminal RRM of the U1A protein and stem loop 2 of U1 snRNA. Previously, we found that substitution of one of these conserved aromatic amino acids, Phe56, with Ala resulted in a large destabilization of the complex. Here, we have modified A6, the base in stem loop 2 RNA that stacks with Phe56, to compensate for a portion of the destabilization caused by the Phe56Ala mutation. We have designed two modified adenosines, A-3CPh and A-4CPh, in which a phenyl group is linked to the adenosine such that it may replace the phenyl group that is eliminated by the Phe56Ala mutation in the complex. We have found that incorporation of A-3CPh into stem loop 2 RNA stabilizes the complex formed with Phe56Ala by 0.6 kcal/mol, while incorporation of A-4CPh into stem loop 2 RNA stabilizes this complex by 1.8 kcal/mol. Either base modification destabilizes the wild-type complex by 0.8-0.9 kcal/mol. Experiments with other U1 A mutant proteins suggest that the stabilization of the complex between the Phe56Ala U1 A protein and stem loop 2 RNA is due to a specific interaction between the Phe56Ala U1A protein and A6-4CPh stem loop 2 RNA.