adenosine 5'-(α,β-methylene)diphosphate | 102977-56-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: adenosine 5'-(α,β-methylene)diphosphate
• CAS: 102977-56-0
• 化学式: C₁₄H₂₁N₅O₁₀P₂
• 分子量: 481.296
• InChiKey: PTOUKBKRYNWCDZ-ZITJMAHISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.25
• 重原子数：
  31.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  210.6
• 氢给体数：
  4.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  2-[2,3-O-(1-甲基乙亚基)-beta-D-呋喃核糖基]-4-噻唑甲酰胺 、 adenosine 5'-(α,β-methylene)diphosphate 在 三正丁胺 、 cation-exchange resin AG₅₀W-X₈ 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 生成 adenosine 5'- 5'<*>5'-ester with 2-β-D-ribofuranosyl-4-thiazolecarboxamide
  参考文献：
  名称：

  Thiazole-4-carboxamide adenine dinucleotide (TAD). Analogs stable to phosphodiesterase hydrolysis

  摘要：

  Thiazole-4-carboxamide adenine dinucleotide (TAD), the active metabolite of the oncolytic C-nucleoside tiazofurin (TR), is susceptible to phosphodiesteratic breakdown by a unique phosphodiesterase present at high levels in TR-resistant tumors. Since accumulation of TAD, as regulated by its synthetic and degradative enzymes, appears to be an important determinant for sensitivity to the drug, a series of hydrolytically resistant phosphonate analogues of TAD were synthesized with the intent of producing more stable compounds with an ability to inhibit IMP dehydrogenase equivalent to TAD itself. Isosteric phosphonic acid analogues of TR and adenosine nucleotides were coupled with activated forms of AMP and TR monophosphate to give dinucleotides 2 and 4. Coupling of protected adenosine 5'-(alpha, beta-methylene)diphosphate with isopropylidene-TR in the presence of DCC afforded compound 3 after deprotection. These compounds are more resistant than TAD toward hydrolysis and still retain potent activity against IMP dehydrogenase in vitro. beta-Methylene-TAD (3), the most stable of the TAD phosphonate analogues, produced a depletion of guanine nucleotide pools in an experimentally induced TR-resistant P388 tumor variant that was superior to that obtained with TR in the corresponding sensitive line.

  DOI：

  10.1021/jm00159a027
• 作为产物：
  描述：

  原甲酸三乙酯 、 alpha,beta-亚甲基腺苷 5'-二磷酸酯 在 三氟乙酸 作用下， 以 二甲基亚砜 为溶剂， 反应 16.0h， 以99%的产率得到adenosine 5'-(α,β-methylene)diphosphate
  参考文献：
  名称：

  Thiazole-4-carboxamide adenine dinucleotide (TAD). Analogs stable to phosphodiesterase hydrolysis

  摘要：

  Thiazole-4-carboxamide adenine dinucleotide (TAD), the active metabolite of the oncolytic C-nucleoside tiazofurin (TR), is susceptible to phosphodiesteratic breakdown by a unique phosphodiesterase present at high levels in TR-resistant tumors. Since accumulation of TAD, as regulated by its synthetic and degradative enzymes, appears to be an important determinant for sensitivity to the drug, a series of hydrolytically resistant phosphonate analogues of TAD were synthesized with the intent of producing more stable compounds with an ability to inhibit IMP dehydrogenase equivalent to TAD itself. Isosteric phosphonic acid analogues of TR and adenosine nucleotides were coupled with activated forms of AMP and TR monophosphate to give dinucleotides 2 and 4. Coupling of protected adenosine 5'-(alpha, beta-methylene)diphosphate with isopropylidene-TR in the presence of DCC afforded compound 3 after deprotection. These compounds are more resistant than TAD toward hydrolysis and still retain potent activity against IMP dehydrogenase in vitro. beta-Methylene-TAD (3), the most stable of the TAD phosphonate analogues, produced a depletion of guanine nucleotide pools in an experimentally induced TR-resistant P388 tumor variant that was superior to that obtained with TR in the corresponding sensitive line.

  DOI：

  10.1021/jm00159a027