2-<(phenylethyl)thio>adenosine | 148527-86-0

• 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-<(phenylethyl)thio>adenosine
• 英文别名: (2R,3R,4S,5R)-2-(6-amino-2-(phenethylthio)-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol；2-(phenylethylthio)adenosine；2-(2-phenylethylthio)adenosine；(2R,3R,4S,5R)-2-[6-amino-2-(2-phenylethylsulfanyl)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 148527-86-0
• 化学式: C₁₈H₂₁N₅O₄S
• 分子量: 403.462
• InChiKey: CXOXIPPSARAPHK-LSCFUAHRSA-N

物化性质

• 熔点：
  205 °C (decomp)
• 沸点：
  785.2±70.0 °C(Predicted)
• 密度：
  1.66±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  165
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-<(phenylethyl)thio>adenosine 在 磷酸三甲酯 、 1,8-双二甲氨基萘 、 三氯氧磷 作用下， 反应 5.0h， 生成
  参考文献：
  名称：

  核苷5'-单磷酸盐作为被ecto-5'-核苷酸酶激活的腺苷A 2A受体激动剂的前药† † 为庆祝美国化学学会药物化学100周年而做的贡献。

  摘要：

  开发了腺苷A 2A受体激动剂的前药，它们被ecto-5'-核苷酸酶（ecto-5'-NT，CD73）激活。由于ecto-5'-NT在发炎的组织中上调，因此A 2A激动剂有望在炎症部位从其前药形式释放出来。合成并研究了2-（Ar）烷基取代的AMP衍生物。某些2-取代的AMP衍生物，包括2-己基硫基-AMP，2-环戊基硫基-AMP，2-环己基甲硫基-AMP和2-环己基乙硫基-AMP被ecto-5'-NT接受为底物，并易于转化为相应的2取代的腺苷衍生物。2-环己基乙硫基取代是ecto-5'-NT和腺苷A 2A的良好折衷方案受体。相应的AMP衍生物（12g）是与AMP本身相似的良好底物，而所得的腺苷衍生物（11g）是相对有效的A 2A激动剂（放射配体与大鼠脑纹状体膜的结合力：K i = 372 nM；抑制抗-在小鼠CD4 +细胞中CD3 /抗CD28诱导的IFN-γ释放：EC 50 = 50 nM

  DOI：

  10.1021/jm900538v
• 作为产物：
  描述：

  (2R,3R,4S,5R)-2-(6-氨基-7-氧代嘌呤-7-鎓-9-基)-5-(羟基甲基)四氢呋喃-3,4-二醇 在 sodium hydroxide 、 三乙胺 作用下， 反应 8.0h， 生成 2-<(phenylethyl)thio>adenosine
  参考文献：
  名称：

  Identification of potent, selective P2Y-purinoceptor agonists: structure-activity relationships for 2-thioether derivatives of adenosine 5'-triphosphate

  摘要：

  Study of P-2-purinoceptor subtypes has been difficult due to the lack of potent and selective ligands. With the goal of developing high affinity P-2-purinoceptor-selective agonists, we have synthesized a series of analogues of adenine nucleotides modified on the purine ring as chain-extended 2-thioethers or as N-6-methyl-substituted compounds. Chemical functionality incorporated in the thioether moiety included cyanoalkyl, nitroaromatic, amino, thiol, cycloalkyl, n-alkyl, and olefinic groups. Apparent affinity of the compounds for P-2Y-purinoceptors was established by measurement of P-2Y-purinoceptor-promoted phospholipase C activity in turkey erythrocyte membranes and relaxation of carbachol-contracted smooth muscle in three different preparations (guinea pig taenia coli, rabbit aorta, and rabbit mesenteric artery). Activity at P-2X-purinoceptors was established by measurement of contraction of rabbit saphenous artery and of the guinea pig vas deferens and urinary bladder. All 11 of the 2-thioethers of ATP stimulated the production of inositol phosphates with K-0.5 values of 1.5-770 nM, with an (aminophenyl)ethyl derivative being most potent. Two adenosine diphosphate analogues were equipotent to the corresponding ATP analogues. Adenosine monophosphate analogues were full agonists, although generally 4 orders of magnitude less potent. ATP 2-thioethers displayed pD(2) values in the range of 6-8 in smooth muscle assay systems for activity at P-2Y-receptors. There was a significant correlation for the 2-thioether compounds between the pK(0.5) values for inositol phosphate production and the pD(2) values for relaxation mediated via the P-2Y-purinoceptors in the guinea pig taenia coli, but not for the vascular P-2Y-receptors or for the P-2X-receptors. At P-2X-receptors, no activity was observed in the rabbit saphenous artery, but variable degrees of activity were observed in the guinea pig vas deferens and bladder depending on distal substituents of the thioether moiety. N-6-Methyl-ATP was inactive at P-2X-receptors, and approximately equipotent to ATP at taenia coli P-2Y-receptors. This suggested that hybrid N-6-methyl and 2-thioether ATP derivatives might be potent and selective for certain P-2Y-receptors, as was shown for one such derivative, N-6-methyl-2-(5-hexenylthio)-ATP.

  DOI：

  10.1021/jm00076a023

文献信息

• 10.1002/chem.202401774
  作者：Ge, Yuhua、Peng, Yijiang、Xie, Ruoqian、Luo, Yang、Li, Yangyan、Chen, Gang

  DOI：10.1002/chem.202401774

  日期：——

  We present herein a novel photo‐mediated homolytic C‐S bond formation for the preparation of alkylthiopurines and alkylthiopurine nucleosides. Despite the presence of reactive sites for the Minisci reaction, chemoselective S‐alkylation remained the predominant pathway. This method allows for the late‐stage introduction of a broad spectrum of alkyl groups onto the sulfur atom of unprotective mercaptopurine derivatives, encompassing 2‐, 6‐, and 8‐mercaptopurine rings. Organoborons serve as efficient and eco‐friendly alkylating reagents, providing advantages in terms of readily availability, stability, and reduced toxicity. Further derivatization of the thioetherified nucleosides, together with anti‐tumor assays, led to the discovery of potent anti‐tumor agents with an IC50 value reaching 6.1 µM (Comp. 31 for Jurkat).
• Nucleoside-5′-monophosphates as Prodrugs of Adenosine A_2A Receptor Agonists Activated by ecto-5′-Nucleotidase†Contribution to celebrate the 100th anniversary of the Division of Medicinal Chemistry of the American Chemical Society.
  作者：Ali El-Tayeb、Jamshed Iqbal、Andrea Behrenswerth、Michael Romio、Marion Schneider、Herbert Zimmermann、Jürgen Schrader、Christa E. Müller

  DOI：10.1021/jm900538v

  日期：2009.12.10

  Prodrugs of adenosine A2A receptor agonists were developed that are activated by ecto-5′-nucleotidase (ecto-5′-NT, CD73). Because ecto-5′-NT is upregulated in inflamed tissue, the A2A agonists are expected to be released from their prodrug form at the sites of inflammation. 2-(Ar)alkyl-substituted AMP derivatives were synthesized and investigated. Certain 2-substituted AMP derivatives, including 2-hexylthio-AMP

  开发了腺苷A 2A受体激动剂的前药，它们被ecto-5'-核苷酸酶（ecto-5'-NT，CD73）激活。由于ecto-5'-NT在发炎的组织中上调，因此A 2A激动剂有望在炎症部位从其前药形式释放出来。合成并研究了2-（Ar）烷基取代的AMP衍生物。某些2-取代的AMP衍生物，包括2-己基硫基-AMP，2-环戊基硫基-AMP，2-环己基甲硫基-AMP和2-环己基乙硫基-AMP被ecto-5'-NT接受为底物，并易于转化为相应的2取代的腺苷衍生物。2-环己基乙硫基取代是ecto-5'-NT和腺苷A 2A的良好折衷方案受体。相应的AMP衍生物（12g）是与AMP本身相似的良好底物，而所得的腺苷衍生物（11g）是相对有效的A 2A激动剂（放射配体与大鼠脑纹状体膜的结合力：K i = 372 nM；抑制抗-在小鼠CD4 +细胞中CD3 /抗CD28诱导的IFN-γ释放：EC 50 = 50 nM
• Identification of potent, selective P2Y-purinoceptor agonists: structure-activity relationships for 2-thioether derivatives of adenosine 5'-triphosphate
  作者：Bilha Fischer、Jose L. Boyer、Charles H. V. Hoyle、Airat U. Ziganshin、Antonia L. Brizzolara、Gillian E. Knight、Jeffrey Zimmet、Geoffrey Burnstock、T. Kendall Harden、Kenneth A. Jacobson

  DOI：10.1021/jm00076a023

  日期：1993.11

  Study of P-2-purinoceptor subtypes has been difficult due to the lack of potent and selective ligands. With the goal of developing high affinity P-2-purinoceptor-selective agonists, we have synthesized a series of analogues of adenine nucleotides modified on the purine ring as chain-extended 2-thioethers or as N-6-methyl-substituted compounds. Chemical functionality incorporated in the thioether moiety included cyanoalkyl, nitroaromatic, amino, thiol, cycloalkyl, n-alkyl, and olefinic groups. Apparent affinity of the compounds for P-2Y-purinoceptors was established by measurement of P-2Y-purinoceptor-promoted phospholipase C activity in turkey erythrocyte membranes and relaxation of carbachol-contracted smooth muscle in three different preparations (guinea pig taenia coli, rabbit aorta, and rabbit mesenteric artery). Activity at P-2X-purinoceptors was established by measurement of contraction of rabbit saphenous artery and of the guinea pig vas deferens and urinary bladder. All 11 of the 2-thioethers of ATP stimulated the production of inositol phosphates with K-0.5 values of 1.5-770 nM, with an (aminophenyl)ethyl derivative being most potent. Two adenosine diphosphate analogues were equipotent to the corresponding ATP analogues. Adenosine monophosphate analogues were full agonists, although generally 4 orders of magnitude less potent. ATP 2-thioethers displayed pD(2) values in the range of 6-8 in smooth muscle assay systems for activity at P-2Y-receptors. There was a significant correlation for the 2-thioether compounds between the pK(0.5) values for inositol phosphate production and the pD(2) values for relaxation mediated via the P-2Y-purinoceptors in the guinea pig taenia coli, but not for the vascular P-2Y-receptors or for the P-2X-receptors. At P-2X-receptors, no activity was observed in the rabbit saphenous artery, but variable degrees of activity were observed in the guinea pig vas deferens and bladder depending on distal substituents of the thioether moiety. N-6-Methyl-ATP was inactive at P-2X-receptors, and approximately equipotent to ATP at taenia coli P-2Y-receptors. This suggested that hybrid N-6-methyl and 2-thioether ATP derivatives might be potent and selective for certain P-2Y-receptors, as was shown for one such derivative, N-6-methyl-2-(5-hexenylthio)-ATP.