N⁶-4-monomethoxytrityl-9-[2-(cycloSal-phosphonylmethoxy)ethyl]adenine | 872191-06-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N⁶-4-monomethoxytrityl-9-[2-(cycloSal-phosphonylmethoxy)ethyl]adenine
• 英文别名: N-[(4-methoxyphenyl)-diphenylmethyl]-9-[2-[(2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-2-yl)methoxy]ethyl]purin-6-amine；N-[(4-methoxyphenyl)-diphenylmethyl]-9-[2-[(2-oxo-4H-1,3,2λ5-benzodioxaphosphinin-2-yl)methoxy]ethyl]purin-6-amine
• CAS: 872191-06-5
• 化学式: C₃₅H₃₂N₅O₅P
• 分子量: 633.643
• InChiKey: HKNBNDGCLIJBLD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  46
• 可旋转键数：
  11
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N⁶-4-monomethoxytrityl-9-[2-(cycloSal-phosphonylmethoxy)ethyl]adenine 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 9-[2-cycloSal-phosphonylmethoxyethyl]adenine
  参考文献：
  名称：

  cycloSal-PMEA and cycloAmb-PMEA:  Potentially New Phosphonate Prodrugs Based on the cycloSal-Pronucleotide Approach

  摘要：

  Two new classes of lipophilic prodrugs of the antiviral active phosphonate 9-[2-phosphonomethoxyethyl] adenine (PMEA 1) have been prepared and were studied with regard to their hydrolysis properties and biological activity. A first series of compounds was prepared on the basis of the cycloSal nucleotide approach. Because of the surprisingly low hydrolysis stability of these cycloSal-PMEA derivatives, more stable derivatives have to be developed. Instead of using salicyl alcohol, in cycloAmb-PMEA derivatives 2-aminobenzyl alcohols were attached to PMEA 1. The latter compounds showed a considerably higher stability compared to the cycloSal counterparts. Stability studies revealed that all lipophilic prodrugs delivered PMEA selectively by chemical means. All compounds proved to be noninhibiting to acetyl- and butyryleholinesterase, and some of the phosphonate diesters were found to be more active against HIV compared to the parent PMEA.

  DOI：

  10.1021/jm050641a
• 作为产物：
  描述：

  4-甲氧基三苯基氯甲烷 在 吡啶 、 4-二甲氨基吡啶 、 五氯化磷 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 22.5h， 生成 N⁶-4-monomethoxytrityl-9-[2-(cycloSal-phosphonylmethoxy)ethyl]adenine
  参考文献：
  名称：

  cycloSal-PMEA and cycloAmb-PMEA:  Potentially New Phosphonate Prodrugs Based on the cycloSal-Pronucleotide Approach

  摘要：

  Two new classes of lipophilic prodrugs of the antiviral active phosphonate 9-[2-phosphonomethoxyethyl] adenine (PMEA 1) have been prepared and were studied with regard to their hydrolysis properties and biological activity. A first series of compounds was prepared on the basis of the cycloSal nucleotide approach. Because of the surprisingly low hydrolysis stability of these cycloSal-PMEA derivatives, more stable derivatives have to be developed. Instead of using salicyl alcohol, in cycloAmb-PMEA derivatives 2-aminobenzyl alcohols were attached to PMEA 1. The latter compounds showed a considerably higher stability compared to the cycloSal counterparts. Stability studies revealed that all lipophilic prodrugs delivered PMEA selectively by chemical means. All compounds proved to be noninhibiting to acetyl- and butyryleholinesterase, and some of the phosphonate diesters were found to be more active against HIV compared to the parent PMEA.

  DOI：

  10.1021/jm050641a

文献信息

• <i>cyclo</i>Sal-PMEA and <i>c</i><i>yclo</i>Amb-PMEA:  Potentially New Phosphonate Prodrugs Based on the <i>cyclo</i>Sal-Pronucleotide Approach
  作者：Chris Meier、Ulf Görbig、Christian Müller、Jan Balzarini

  DOI：10.1021/jm050641a

  日期：2005.12.1

  Two new classes of lipophilic prodrugs of the antiviral active phosphonate 9-[2-phosphonomethoxyethyl] adenine (PMEA 1) have been prepared and were studied with regard to their hydrolysis properties and biological activity. A first series of compounds was prepared on the basis of the cycloSal nucleotide approach. Because of the surprisingly low hydrolysis stability of these cycloSal-PMEA derivatives, more stable derivatives have to be developed. Instead of using salicyl alcohol, in cycloAmb-PMEA derivatives 2-aminobenzyl alcohols were attached to PMEA 1. The latter compounds showed a considerably higher stability compared to the cycloSal counterparts. Stability studies revealed that all lipophilic prodrugs delivered PMEA selectively by chemical means. All compounds proved to be noninhibiting to acetyl- and butyryleholinesterase, and some of the phosphonate diesters were found to be more active against HIV compared to the parent PMEA.