N⁹-<1-fluoro-4-<(2-tetrahydropyranyl)oxy>-2-butyn-1-yl>adenine | 162106-12-9

• 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: N⁹-<1-fluoro-4-<(2-tetrahydropyranyl)oxy>-2-butyn-1-yl>adenine
• 英文别名: 9-[1-Fluoro-4-(oxan-2-yloxy)but-2-ynyl]purin-6-amine
• CAS: 162106-12-9
• 化学式: C₁₄H₁₆FN₅O₂
• 分子量: 305.312
• InChiKey: AWKVPFGIZKHNES-UHFFFAOYSA-N

物化性质

• 沸点：
  549.4±60.0 °C(predicted)
• 密度：
  1.45±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  88.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N⁹-<1-fluoro-4-<(2-tetrahydropyranyl)oxy>-2-butyn-1-yl>adenine 在 水 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以87%的产率得到N⁹-(1-fluoro-4-hydroxy-2-butyn-1-yl)adenine
  参考文献：
  名称：

  Unsaturated Acyclic Analogs of 2'-Deoxyadenosine and Thymidine Containing Fluorine: Synthesis and Biological Activity

  摘要：

  The syntheses and biological activities of fluorobutynol 11 and (E)- and (Z)-fluorobutenols 8a,d and 9a,d are described. Alkylation of adenine with bromofluorobutyne 13a afforded intermediate 14 which was converted to fluorobutynol 11. Aldehyde 16a and (carbothoxyfluoromethyl)triphenylphosphonium bromide furnished (E)- and (Z)-fluorobutenoates 19a and 20a accompanied by regioisomer 21a. A similar reaction of compound 16d afforded Z- and E-esters 19d and 20d. Reduction of the mixture of 19a and 20a with DIBALH gave (E)- and (Z)-fluoroalkenols 8a and 9a. Similarly, the Z-ester 19d gave (Z)-fluoroalkenol 9d. Both 19d and 20d were reduced with NaBH4 to give (Z)- and (E)-fluoroalkenols 9d and 8d. Hydrogenation of 19a and 20a afforded fluoro ester 23. A similar reduction of 8a and 9a led to fluoro alcohol 24 and the defluorinated product 25 which were separated by chromatography on a Bio-Rad AG 1-X2 (OH-) column. (Z)-Fluorobutenol 9a is a substrate for adenosine deaminase, whereas the E-isomer 8a is inert toward the enzyme. By contrast, analogue 8a inhibited the replication and cytopathic effect of HN-1 in ATH8 cells with an IC50 Of approximately 100 mu M, but the Z-isomer 9a was inactive. This effect was accompanied by 36% cytotoxicity at 100 mu M. Compounds 11 and 8d inhibited the growth of murine leukemia L1210 culture with IC50 = 89 and 60 mu M, respectively.

  DOI：

  10.1021/jm00006a004
• 作为产物：
  描述：

  哌喃 在 正丁基锂 、 sodium hydride 作用下， 反应 21.5h， 生成 N⁹-<1-fluoro-4-<(2-tetrahydropyranyl)oxy>-2-butyn-1-yl>adenine
  参考文献：
  名称：

  Unsaturated Acyclic Analogs of 2'-Deoxyadenosine and Thymidine Containing Fluorine: Synthesis and Biological Activity

  摘要：

  The syntheses and biological activities of fluorobutynol 11 and (E)- and (Z)-fluorobutenols 8a,d and 9a,d are described. Alkylation of adenine with bromofluorobutyne 13a afforded intermediate 14 which was converted to fluorobutynol 11. Aldehyde 16a and (carbothoxyfluoromethyl)triphenylphosphonium bromide furnished (E)- and (Z)-fluorobutenoates 19a and 20a accompanied by regioisomer 21a. A similar reaction of compound 16d afforded Z- and E-esters 19d and 20d. Reduction of the mixture of 19a and 20a with DIBALH gave (E)- and (Z)-fluoroalkenols 8a and 9a. Similarly, the Z-ester 19d gave (Z)-fluoroalkenol 9d. Both 19d and 20d were reduced with NaBH4 to give (Z)- and (E)-fluoroalkenols 9d and 8d. Hydrogenation of 19a and 20a afforded fluoro ester 23. A similar reduction of 8a and 9a led to fluoro alcohol 24 and the defluorinated product 25 which were separated by chromatography on a Bio-Rad AG 1-X2 (OH-) column. (Z)-Fluorobutenol 9a is a substrate for adenosine deaminase, whereas the E-isomer 8a is inert toward the enzyme. By contrast, analogue 8a inhibited the replication and cytopathic effect of HN-1 in ATH8 cells with an IC50 Of approximately 100 mu M, but the Z-isomer 9a was inactive. This effect was accompanied by 36% cytotoxicity at 100 mu M. Compounds 11 and 8d inhibited the growth of murine leukemia L1210 culture with IC50 = 89 and 60 mu M, respectively.

  DOI：

  10.1021/jm00006a004

文献信息

• Unsaturated Acyclic Analogs of 2'-Deoxyadenosine and Thymidine Containing Fluorine: Synthesis and Biological Activity
  作者：Ze-Qi Xu、Yao-Ling Qiu、Sudhichai Chokekijchai、Hiroaki Mitsuya、Jiri Zemlicka

  DOI：10.1021/jm00006a004

  日期：1995.3

  The syntheses and biological activities of fluorobutynol 11 and (E)- and (Z)-fluorobutenols 8a,d and 9a,d are described. Alkylation of adenine with bromofluorobutyne 13a afforded intermediate 14 which was converted to fluorobutynol 11. Aldehyde 16a and (carbothoxyfluoromethyl)triphenylphosphonium bromide furnished (E)- and (Z)-fluorobutenoates 19a and 20a accompanied by regioisomer 21a. A similar reaction of compound 16d afforded Z- and E-esters 19d and 20d. Reduction of the mixture of 19a and 20a with DIBALH gave (E)- and (Z)-fluoroalkenols 8a and 9a. Similarly, the Z-ester 19d gave (Z)-fluoroalkenol 9d. Both 19d and 20d were reduced with NaBH4 to give (Z)- and (E)-fluoroalkenols 9d and 8d. Hydrogenation of 19a and 20a afforded fluoro ester 23. A similar reduction of 8a and 9a led to fluoro alcohol 24 and the defluorinated product 25 which were separated by chromatography on a Bio-Rad AG 1-X2 (OH-) column. (Z)-Fluorobutenol 9a is a substrate for adenosine deaminase, whereas the E-isomer 8a is inert toward the enzyme. By contrast, analogue 8a inhibited the replication and cytopathic effect of HN-1 in ATH8 cells with an IC50 Of approximately 100 mu M, but the Z-isomer 9a was inactive. This effect was accompanied by 36% cytotoxicity at 100 mu M. Compounds 11 and 8d inhibited the growth of murine leukemia L1210 culture with IC50 = 89 and 60 mu M, respectively.

表征谱图