2-phenylamino-9-{4-[4-hydroxy-4-(4-chloro-3-trifluoromethylphenyl)piperidyl]butyl}-6-oxopurine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-phenylamino-9-{4-[4-hydroxy-4-(4-chloro-3-trifluoromethylphenyl)piperidyl]butyl}-6-oxopurine
• 英文别名: 2-anilino-9-[4-[4-[4-chloro-3-(trifluoromethyl)phenyl]-4-hydroxy-1-piperidyl]butyl]-1H-purin-6-one；2-anilino-9-[4-[4-[4-chloro-3-(trifluoromethyl)phenyl]-4-hydroxypiperidin-1-yl]butyl]-1H-purin-6-one
• 化学式: C₂₇H₂₈ClF₃N₆O₂
• 分子量: 561.007
• InChiKey: NXTQVMUVBFNMQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  94.8
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-苯胺基-9-(4-羟基丁基)-3H-嘌呤-6-酮 在 碘代三甲硅烷 、 potassium carbonate 作用下， 以 环丁砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 2-phenylamino-9-{4-[4-hydroxy-4-(4-chloro-3-trifluoromethylphenyl)piperidyl]butyl}-6-oxopurine
  参考文献：
  名称：

  Inhibition of Herpes Simplex Virus Thymidine Kinases by 2-Phenylamino-6-oxopurines and Related Compounds:  Structure−Activity Relationships and Antiherpetic Activity in Vivo

  摘要：

  Derivatives of the herpes simplex thymidine kinase inhibitor HBPG [2-phenylamino-9-(4-hydroxybutyl)-6-oxopurine] have been synthesized and tested for inhibitory activity against recombinant enzymes (TK) from herpes simplex types 1 and 2 (HSV-1, HSV-2). The compounds inhibited phosphorylation of [H-3]thymidine by both enzymes, but potencies differed quantitatively from those of HBPG and were generally greater for HSV-2 than HSV-1 TKs. Changes in inhibitory potency were generally consistent with the inhibitor/substrate binding site structure based on published X-ray structures of HSV-1 TK. In particular, several 9-(4-aminobutyl) analogues with bulky tertiary amino substituents were among the most potent inhibitors. Variable substrate assays showed that the most potent compound, 2-phenylamino-9-[4-(1-decahydroquinolyl)butyl]-6-oxopurine, was a competitive inhibitor, with K-i values of 0.03 and 0.005 mu M against HSV-1 and HSV-2 TKs, respectively. The parent compound HBPG was uniquely active in viral infection models in mice, both against ocular HSV-2 reactivation and against HSV-1 and HSV-2 encephalitis. In assays lacking [H-3]thymidine, HBPG was found to be an efficient substrate for the enzymes. The ability of the TKs to phosphorylate HBPG may relate to its antiherpetic activity in vivo.

  DOI：

  10.1021/jm049059x