(Z)-9-{[2-(acetoxymethyl)-2-(hydroxymethyl)cyclopropylidene]methyl}guanine | 841275-60-3

• 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: (Z)-9-{[2-(acetoxymethyl)-2-(hydroxymethyl)cyclopropylidene]methyl}guanine
• 英文别名: [(2Z)-2-[(2-amino-6-oxo-1H-purin-9-yl)methylidene]-1-(hydroxymethyl)cyclopropyl]methyl acetate
• CAS: 841275-60-3
• 化学式: C₁₃H₁₅N₅O₄
• 分子量: 305.293
• InChiKey: NTLIXMOCFUVEHA-BAQGIRSFSA-N

物化性质

• 沸点：
  593.9±60.0 °C(Predicted)
• 密度：
  1.68±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  132
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (Z)-9-{[2-(acetoxymethyl)-2-(hydroxymethyl)cyclopropylidene]methyl}guanine 在 吡啶 、 N-甲基咪唑 、 ammonium hydroxide 、 甲烷磺酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 115.5h， 生成 (Z)-9-{[(2,2-hydroxymethyl)cyclopropylidene]methyl}guanine (methylphenylphosphoryl) P-N-L-alaninate
  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：

  2-Amino-9-[6-methoxy-6-methyl-5,7-dioxa-spiro[2.5]oct-(1Z)-ylidenemethyl]-1,9-dihydro-purin-6-one 在 溶剂黄146 作用下， 反应 10.0h， 以1.78 g的产率得到(Z)-9-{[2-(acetoxymethyl)-2-(hydroxymethyl)cyclopropylidene]methyl}guanine
  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

文献信息

• WO2019172835A5
  申请人：——

  公开号：WO2019172835A5

  公开（公告）日：2022-03-16
• CANCER TREATMENT WITH (2,2-BISHYDROXYMETHYL) METHYLENECYCLOPROPANE NUCLEOTIDES
  申请人：Medivir Aktiebolag

  公开号：EP3762394A1

  公开（公告）日：2021-01-13
• [EN] CANCER TREATMENT WITH (2,2-BISHYDROXYMETHYL) METHYLENECYCLOPROPANE NUCLEOTIDES<br/>[FR] TRAITEMENT DU CANCER À L'AIDE DE NUCLÉOTIDES DE (2,2-BISHYDROXYMÉTHYL) MÉTHYLÈNECYCLOPROPANE
  申请人：MEDIVIR AB

  公开号：WO2019172835A1

  公开（公告）日：2019-09-12

  The invention provides a compound of formula (I) wherein B is a nucleobase; U is O or S; Rx is -OC(=O)Ry, -OC(=O)CH(Ry)NH2, -OCH2OC(=O)Ry; Ry is optionally substituted alkyl or alkenyl or the side chain of a natural or unnatural amino acid R1 is H, or optionally substituted phenyl, benzyl, naphthyl, pyridyl or indolyl, or Rx and R1 together define a bond thus forming a cyclic phosphate; R2 and R2' together define the side chain of a natural or unnatural amino acid; R3 is optionally substituted alkyl, cycloalkyl, phenyl or benzyl; and pharmaceutically acceptable salts and compositions thereof which are useful in the treatment of cancer, especially leukemias.