N⁶-methyl-2-(5-hexenylthio)adenosine | 151565-99-0

• 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: N⁶-methyl-2-(5-hexenylthio)adenosine
• 英文别名: (2R,3R,4S,5R)-2-[2-hex-5-enylsulfanyl-6-(methylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 151565-99-0
• 化学式: C₁₇H₂₅N₅O₄S
• 分子量: 395.483
• InChiKey: MKELXHLNEHQYLD-XNIJJKJLSA-N

物化性质

• 沸点：
  722.1±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)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  151
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N⁶-methyl-2-(5-hexenylthio)adenosine 在 磷酸三甲酯 、 Proton Sponge 、 三正丁胺 、 三乙基碳酸氢铵缓冲液 、 三丁基焦磷酸铵 、 三氯氧磷 作用下， 生成 N⁶-methyl-2-(5-hexenylthio)adenosine monophosphate monoammonium salt 、 N⁶-methyl-2-(5-hexenylthio)adenosine 5'-triphosphate tetraammonium salt
  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
• 作为产物：
  描述：

  N1-Oxy-N6-methyl-adenosine 在 sodium hydroxide 作用下， 反应 8.0h， 生成 N⁶-methyl-2-(5-hexenylthio)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