(E)-9-{[2-(hydroxymethyl)-2-(tetrahydropyranyloxymethyl)cyclopropylidene]methyl}adenine | 841275-66-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (E)-9-{[2-(hydroxymethyl)-2-(tetrahydropyranyloxymethyl)cyclopropylidene]methyl}adenine
• 英文别名: [(2E)-2-[(6-aminopurin-9-yl)methylidene]-1-(oxan-2-yloxymethyl)cyclopropyl]methanol
• CAS: 841275-66-9
• 化学式: C₁₆H₂₁N₅O₃
• 分子量: 331.374
• InChiKey: MAWGZSBCTZIGDV-IZZDOVSWSA-N

物化性质

• 沸点：
  599.7±60.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (E)-9-{[2-(hydroxymethyl)-2-(tetrahydropyranyloxymethyl)cyclopropylidene]methyl}adenine 在 吡啶 、 N-甲基咪唑 、 porcine liver esterase 、 disodium hydrogenphosphate 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 反应 5.0h， 生成 (S)-2-({2-[1-(6-Amino-purin-9-yl)-meth-(E)-ylidene]-1-hydroxymethyl-cyclopropylmethoxy}-phenoxy-phosphorylamino)-propionic acid
  参考文献：
  名称：

  Nucleotides and Pronucleotides of 2,2-Bis(hydroxymethyl)methylenecyclopropane Analogues of Purine Nucleosides:  Synthesis and Antiviral Activity

  摘要：

  Phenylmethylphosphor-L-alaninate pronucleotides 7a, 7b, 8a, and 8b, cyclic phosphates 10a and 10b, and phosphates 11a and 11b derived from 2,2-bis(hydroxymethyl)methylenecyclopropane analogues 1a, 1b, 2a, and 2b were synthesized and evaluated for their antiviral activity. An improved protocol for the synthesis of analogues 1a, 1b, 2a, and 2b is also described. Phosphate 11a was the most effective agent against human and murine cytomegalovirus (EC50 0.25-1.1 muM). The Z-pronucleotides 7a and 7b had EC50 3.6-25.2 and 3-18.4 muM, respectively. The EC50 of cyclic phosphate 10a was 6.0-20 muM. The activity against Epstein-Barr (EBV) was assay-dependent. Pronucleotides 7a and 7b and phosphate 11a had EC50 2.3-3.4 muM against EBV/H-1, but 7b was cytotoxic (CC50 3.8 muM). Cyclic phosphate 10a was the only compound effective against EBV/Daudi (EC50 0.96 muM). but it was inactive in H-1 cells. Pronucleotide 7a was active against varicella zoster virus with EC50 6.3 and 7.3 muM, respectively. and hepatitis B virus (HBV, EC50 4.1 muM). Cyclic phosphate 10a was the most effective analogue against HBV (EC50 0.8 muM).

  DOI：

  10.1021/jm040149b
• 作为产物：
  描述：

  Acetic acid 2-[1-(6-amino-purin-9-yl)-meth-(E)-ylidene]-1-(tetrahydro-pyran-2-yloxymethyl)-cyclopropylmethyl ester 在 ammonium hydroxide 作用下， 以 甲醇 为溶剂， 以1.10 g的产率得到(E)-9-{[2-(hydroxymethyl)-2-(tetrahydropyranyloxymethyl)cyclopropylidene]methyl}adenine
  参考文献：
  名称：

  Nucleotides and Pronucleotides of 2,2-Bis(hydroxymethyl)methylenecyclopropane Analogues of Purine Nucleosides:  Synthesis and Antiviral Activity

  摘要：

  Phenylmethylphosphor-L-alaninate pronucleotides 7a, 7b, 8a, and 8b, cyclic phosphates 10a and 10b, and phosphates 11a and 11b derived from 2,2-bis(hydroxymethyl)methylenecyclopropane analogues 1a, 1b, 2a, and 2b were synthesized and evaluated for their antiviral activity. An improved protocol for the synthesis of analogues 1a, 1b, 2a, and 2b is also described. Phosphate 11a was the most effective agent against human and murine cytomegalovirus (EC50 0.25-1.1 muM). The Z-pronucleotides 7a and 7b had EC50 3.6-25.2 and 3-18.4 muM, respectively. The EC50 of cyclic phosphate 10a was 6.0-20 muM. The activity against Epstein-Barr (EBV) was assay-dependent. Pronucleotides 7a and 7b and phosphate 11a had EC50 2.3-3.4 muM against EBV/H-1, but 7b was cytotoxic (CC50 3.8 muM). Cyclic phosphate 10a was the only compound effective against EBV/Daudi (EC50 0.96 muM). but it was inactive in H-1 cells. Pronucleotide 7a was active against varicella zoster virus with EC50 6.3 and 7.3 muM, respectively. and hepatitis B virus (HBV, EC50 4.1 muM). Cyclic phosphate 10a was the most effective analogue against HBV (EC50 0.8 muM).

  DOI：

  10.1021/jm040149b