2-(6-amino-2-(p-nitrophenylethyl)sulfanyl-7H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol | 151566-00-6

• 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-(6-amino-2-(p-nitrophenylethyl)sulfanyl-7H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
• 英文别名: 2-<2-(p-nitrophenethyl)thio>adenosine；2-(p-nitrophenylethyl)thio adenosine；2-[2-(p-nitrophenethyl)thio]adenosine；(2R,3R,4S,5R)-2-[6-amino-2-[2-(4-nitrophenyl)ethylsulfanyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 151566-00-6
• 化学式: C₁₈H₂₀N₆O₆S
• 分子量: 448.459
• InChiKey: GQOPKJHQCGOIHY-LSCFUAHRSA-N

物化性质

• 沸点：
  863.2±75.0 °C(Predicted)
• 密度：
  1.80±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  31
• 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：
  211
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  2-(6-amino-2-(p-nitrophenylethyl)sulfanyl-7H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 在 吡啶 、 Proton Sponge 、 三氯氧磷 作用下， 反应 0.25h， 生成 (2R,3R,4S,5R)-2-[6-amino-2-[2-(4-nitrophenyl)ethylsulfanyl]purin-9-yl]-5-(dichlorophosphinothioyloxymethyl)oxolane-3,4-diol
  参考文献：
  名称：

  2-硫醚5'-O-（1-硫代三磷酸）腺苷衍生物作为通过P2Y受体发挥作用的新型胰岛素促分泌剂。

  摘要：

  P2-受体（P2-Rs）代表了新药开发的重要目标。在胰腺B细胞上也鉴定出P2-R，并且它们参与胰岛素分泌。因此，合成了新型的P2Y-R配体2-硫醚5'-O-硫代磷酸腺苷腺苷衍生物（2-RS-ATP-α-S）作为潜在的胰岛素促分泌剂。描述了这些核苷酸的有效合成和分离手性产物的简便方法。评估了化合物对猪胰腺I型ATPDase的酶稳定性。ATPDase水解2-己基硫基5'-O-（1-硫代三磷酸）腺苷（2-己基硫基-ATP-α-S）异构体的速率为ATP的28％。一些2-硫醚5'-（单硫代磷酸酯）腺苷衍生物（2-RS-AMP-S）对ATPDase产生抑制作用。化合物对P2Y（1）-R的表观亲和力是通过测量土耳其红细胞膜中P2Y-R促进的磷脂酶C活性来确定的。2-RS-ATP-α-S衍生物是激动剂，可刺激K（0.5）值在纳摩尔范围内的肌醇磷酸酯的产生。2-RS-AMP-S衍生物是完全的激动剂，尽管效力

  DOI：

  10.1021/jm990158y
• 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-(6-amino-2-(p-nitrophenylethyl)sulfanyl-7H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
  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

• 2-Thioether 5‘-<i>O</i>-(1-Thiotriphosphate)adenosine Derivatives as New Insulin Secretagogues Acting through P2Y-Receptors
  作者：Bilha Fischer、Ana Chulkin、Jose L. Boyer、Kendall T. Harden、Fernand-Pierre Gendron、Adrien R. Beaudoin、Jeannie Chapal、Dominique Hillaire-Buys、Pierre Petit

  DOI：10.1021/jm990158y

  日期：1999.9.1

  (2-RS-ATP-alpha-S), were synthesized as potential insulin secretagogues. An efficient synthesis of these nucleotides and a facile method for separation of the chiral products are described. The enzymatic stability of the compounds toward pig pancreas type I ATPDase was evaluated. The rate of hydrolysis of 2-hexylthio-5'-O-(1-thiotriphosphate)adenosine (2-hexylthio-ATP-alpha-S) isomers by ATPDase was 28% of that of

  P2-受体（P2-Rs）代表了新药开发的重要目标。在胰腺B细胞上也鉴定出P2-R，并且它们参与胰岛素分泌。因此，合成了新型的P2Y-R配体2-硫醚5'-O-硫代磷酸腺苷腺苷衍生物（2-RS-ATP-α-S）作为潜在的胰岛素促分泌剂。描述了这些核苷酸的有效合成和分离手性产物的简便方法。评估了化合物对猪胰腺I型ATPDase的酶稳定性。ATPDase水解2-己基硫基5'-O-（1-硫代三磷酸）腺苷（2-己基硫基-ATP-α-S）异构体的速率为ATP的28％。一些2-硫醚5'-（单硫代磷酸酯）腺苷衍生物（2-RS-AMP-S）对ATPDase产生抑制作用。化合物对P2Y（1）-R的表观亲和力是通过测量土耳其红细胞膜中P2Y-R促进的磷脂酶C活性来确定的。2-RS-ATP-α-S衍生物是激动剂，可刺激K（0.5）值在纳摩尔范围内的肌醇磷酸酯的产生。2-RS-AMP-S衍生物是完全的激动剂，尽管效力
• 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.