(Z)-9-[(2-hydroxymethyl-2-fluoromethylcyclopropylidene)methyl]guanine | 1026676-00-5

• 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-hydroxymethyl-2-fluoromethylcyclopropylidene)methyl]guanine
• 英文别名: 2-amino-9-[(Z)-[2-(fluoromethyl)-2-(hydroxymethyl)cyclopropylidene]methyl]-1H-purin-6-one
• CAS: 1026676-00-5
• 化学式: C₁₁H₁₂FN₅O₂
• 分子量: 265.247
• InChiKey: SPTYJADPUUVWCD-KXFIGUGUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (Z)-2-amino-6-chloro-9-[(2-hydroxymethyl-2-fluoromethylcyclopropylidene)methyl]purine 在 甲酸 作用下， 反应 4.0h， 以84%的产率得到(Z)-9-[(2-hydroxymethyl-2-fluoromethylcyclopropylidene)methyl]guanine
  参考文献：
  名称：

  Fluorinated methylenecyclopropane analogues of nucleosides. Synthesis and antiviral activity of (Z)- and (E)-9-{[(2-fluoromethyl-2-hydroxymethyl)-cyclopropylidene]methyl}adenine and -guanine

  摘要：

  Synthesis and antiviral activity of the title fluoromethylenecyclopropane analogues 15a, 15b, 16a, and 16b is described. Methylenecyclopropane carboxylate was first transformed to 2,2-bis-hydroxymethylmethylenecyclopropane. Selective monoacetylation followed by introduction of fluorine gave 2-acetoxymethyl-2-fluoromethylmethylenecyclopropane as the key inter-mediate. The synthesis of analogues 15a, 15b, 16a, and 16b then followed alkylation-elimination procedure as described previously for other methylenecyclopropane analogues. The adenine Z-isomer 15a was found to be a potent inhibitor of Epstein-Barr virus (EBV) in vitro with EC50/CC50 (mu M) 0.5/55.7. Compounds 15b, 16a, and 16b were also active but at higher concentrations, EC50/CC50 (mu M) 3.2-7.5/53.6-64.1. Analogue 15a inhibited hepatitis C virus by virtue of its cytotoxicity and it moderately inhibited replication of the Towne strain of human cytomegalovirus (HCMV). The E-isomer 16a was a substrate for adenosine deaminase, whereas the Z-isomer 15a was not deaminated. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.082

文献信息

• Fluorinated methylenecyclopropane analogues of nucleosides. Synthesis and antiviral activity of (Z)- and (E)-9-{[(2-fluoromethyl-2-hydroxymethyl)-cyclopropylidene]methyl}adenine and -guanine
  作者：Chengwei Li、Mark N. Prichard、Brent E. Korba、John C. Drach、Jiri Zemlicka

  DOI：10.1016/j.bmc.2007.11.082

  日期：2008.3

  Synthesis and antiviral activity of the title fluoromethylenecyclopropane analogues 15a, 15b, 16a, and 16b is described. Methylenecyclopropane carboxylate was first transformed to 2,2-bis-hydroxymethylmethylenecyclopropane. Selective monoacetylation followed by introduction of fluorine gave 2-acetoxymethyl-2-fluoromethylmethylenecyclopropane as the key inter-mediate. The synthesis of analogues 15a, 15b, 16a, and 16b then followed alkylation-elimination procedure as described previously for other methylenecyclopropane analogues. The adenine Z-isomer 15a was found to be a potent inhibitor of Epstein-Barr virus (EBV) in vitro with EC50/CC50 (mu M) 0.5/55.7. Compounds 15b, 16a, and 16b were also active but at higher concentrations, EC50/CC50 (mu M) 3.2-7.5/53.6-64.1. Analogue 15a inhibited hepatitis C virus by virtue of its cytotoxicity and it moderately inhibited replication of the Towne strain of human cytomegalovirus (HCMV). The E-isomer 16a was a substrate for adenosine deaminase, whereas the Z-isomer 15a was not deaminated. (C) 2007 Elsevier Ltd. All rights reserved.