4-[[(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy]-4-oxobutanoic acid | 109816-77-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 4-[[(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy]-4-oxobutanoic acid
• CAS: 109816-77-5
• 化学式: C₁₇H₂₁N₅O₇
• 分子量: 407.383
• InChiKey: ZPKKFXDWBNPZTK-KWDXPJCYSA-N

物化性质

• 沸点：
  689.2±65.0 °C(Predicted)
• 密度：
  1.73±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  161
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  4-[[(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy]-4-oxobutanoic acid 在 三氟乙酸 作用下， 反应 48.0h， 以53%的产率得到Adenosine monosuccinate
  参考文献：
  名称：

  Potential utility of adenosine 5′-ester prodrugs to enhance its plasma half-life: synthesis and molecular docking studies

  摘要：

  Adenosine, the adenine nucleoside, has demonstrated various pharmacological properties related to the treatment of relevant clinical diseases. With respect to this, one of the most fascinating biological activities of adenosine is its capacity for reversing hepatic fibrosis, which has been established in several in vitro and in vivo studies. Although adenosine seems to be a privileged compound, it lacks of metabolic stability to be considered as a drug candidate. For this reason, in this preliminary study, six prodrugs were developed in order to enhance the plasma half-life of adenosine, in which the esterification at 5' position of adenosine was considered. According to previous works, the increase in steric hindrance at this position could develop unfavorable interactions inside adenosine deaminase (ADA) catalytic domain, which is reported as the main enzyme implicated in adenosine metabolism. Besides, molecular docking was employed to verify if the hindrance at carbinol group in the prodrugs is enough to diminish its oxidation and also to predict if compounds would be metabolized by a promiscuous esterase. Finally, the in vitro assays corroborated the theoretical findings and also indicated that the compounds are less metabolized than adenosine by ADA; in the case of compounds containing proline and thioproline progroups (4d and 4e, respectively), the reduction was more than three-fold of decrease.

  DOI：

  10.1007/s00044-014-1299-z
• 作为产物：
  描述：

  腺苷 在 对甲苯磺酸 、 溶剂黄146 作用下， 以 丙酮 为溶剂， 反应 75.0h， 生成 4-[[(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy]-4-oxobutanoic acid
  参考文献：
  名称：

  Potential utility of adenosine 5′-ester prodrugs to enhance its plasma half-life: synthesis and molecular docking studies

  摘要：

  Adenosine, the adenine nucleoside, has demonstrated various pharmacological properties related to the treatment of relevant clinical diseases. With respect to this, one of the most fascinating biological activities of adenosine is its capacity for reversing hepatic fibrosis, which has been established in several in vitro and in vivo studies. Although adenosine seems to be a privileged compound, it lacks of metabolic stability to be considered as a drug candidate. For this reason, in this preliminary study, six prodrugs were developed in order to enhance the plasma half-life of adenosine, in which the esterification at 5' position of adenosine was considered. According to previous works, the increase in steric hindrance at this position could develop unfavorable interactions inside adenosine deaminase (ADA) catalytic domain, which is reported as the main enzyme implicated in adenosine metabolism. Besides, molecular docking was employed to verify if the hindrance at carbinol group in the prodrugs is enough to diminish its oxidation and also to predict if compounds would be metabolized by a promiscuous esterase. Finally, the in vitro assays corroborated the theoretical findings and also indicated that the compounds are less metabolized than adenosine by ADA; in the case of compounds containing proline and thioproline progroups (4d and 4e, respectively), the reduction was more than three-fold of decrease.

  DOI：

  10.1007/s00044-014-1299-z

文献信息

• Garaeva, L. D.; Goryunova, O. V.; Yartseva, I. V., Russian Journal of Bioorganic Chemistry, 1995, vol. 21, # 9, p. 619 - 625
  作者：Garaeva, L. D.、Goryunova, O. V.、Yartseva, I. V.、Mashalova, N. A.、Melnik, S. Ya.

  DOI：——

  日期：——
• Synthesis and structure-activity relationships of adenosine analogs as inhibitors of trypanosomal glyceraldehyde-3-phosphate dehydrogenase. Modifications at positions 5′ and 8
  作者：Alex M. Aronov、Michael H. Gelb

  DOI：10.1016/s0960-894x(98)00635-0

  日期：1998.12

  A number of 5', N6- and C8, N6-disubstituted adenosine analogs was synthesized and tested for inhibition of trypanosomal glyceraldehyde 3-phosphate dehydrogenase. The most active compound, N6-(3-methyl-2-butenyl)-8-(2-thienyl)adenosine, had Kl of 9 microM and was marginally selective for the parasite enzyme.