2-[3-(Difluoromethyl)anilino]-1,9-dihydropurin-6-one

• 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: 2-[3-(Difluoromethyl)anilino]-1,9-dihydropurin-6-one
• 英文别名: 2-[3-(difluoromethyl)anilino]-1,7-dihydropurin-6-one
• 化学式: C₁₂H₉F₂N₅O
• 分子量: 277.233
• InChiKey: JRLITVMWEMTPRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  82.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  alpha,alpha-二氟-3-硝基甲苯 在 盐酸 、 tin 作用下， 以 乙二醇甲醚 为溶剂， 反应 0.5h， 生成 2-[3-(Difluoromethyl)anilino]-1,9-dihydropurin-6-one
  参考文献：
  名称：

  Synthesis, Properties, and Pharmacokinetic Studies of N2-Phenylguanine Derivatives as Inhibitors of Herpes Simplex Virus Thymidine Kinases

  摘要：

  Two series of selective inhibitors of herpes simplex virus types 1 and 2 (HSV1,2) thymidine kinases (TK) have been developed as potential treatment of recurrent virus infections. Among compounds related to the potent base analog N-2-[m-(trifluoromethyl)phenyl]guanine (mCF(3)PG), none was a more potent inhibitor than mCF(3)PG itself. Compounds related to the nucleoside N-2-phenyl-2'-deoxyguanosine (PhdG), but with alkyl, hydroxyalkyl, and related substituents at the 9-position in place of the glycosyl group of PhdG, retained significant but variable inhibitory potencies against the HSV TKs. The most potent inhibitor of HSV1 TK among 9-substituted derivatives, 9-(4-hydroxybutyl)-N-2-phenylguanine (HBPG), was a competitive inhibitor with respect to the substrate thymidine but was not itself a substrate for the enzyme. Water solubilities and 1-octanol:water partition coefficients for the 9-substituted N-2-phenylguanines were linearly but oppositely related to the sum of hydrophobic fragmental constants (Sigma f) of the 9-substituents. Four of the inhibitors were given as solutions to mice by iv and ip routes, and the time course of their plasma concentrations was determined by HPLC analysis of the parent compounds. HBPG was completely absorbed by the ip route, and the plasma concentration could be prolonged by use of suspension formulations. HBPG is a candidate for animal trials of the ability of TK inhibitors to prevent recurrent herpes virus infections.

  DOI：

  10.1021/jm00001a010

文献信息

• Synthesis, Properties, and Pharmacokinetic Studies of N2-Phenylguanine Derivatives as Inhibitors of Herpes Simplex Virus Thymidine Kinases
  作者：Hongyan Xu、Giovanni Maga、Federico Focher、Emil R. Smith、Silvio Spadari、Joseph Gambino、George E. Wright

  DOI：10.1021/jm00001a010

  日期：1995.1

  Two series of selective inhibitors of herpes simplex virus types 1 and 2 (HSV1,2) thymidine kinases (TK) have been developed as potential treatment of recurrent virus infections. Among compounds related to the potent base analog N-2-[m-(trifluoromethyl)phenyl]guanine (mCF(3)PG), none was a more potent inhibitor than mCF(3)PG itself. Compounds related to the nucleoside N-2-phenyl-2'-deoxyguanosine (PhdG), but with alkyl, hydroxyalkyl, and related substituents at the 9-position in place of the glycosyl group of PhdG, retained significant but variable inhibitory potencies against the HSV TKs. The most potent inhibitor of HSV1 TK among 9-substituted derivatives, 9-(4-hydroxybutyl)-N-2-phenylguanine (HBPG), was a competitive inhibitor with respect to the substrate thymidine but was not itself a substrate for the enzyme. Water solubilities and 1-octanol:water partition coefficients for the 9-substituted N-2-phenylguanines were linearly but oppositely related to the sum of hydrophobic fragmental constants (Sigma f) of the 9-substituents. Four of the inhibitors were given as solutions to mice by iv and ip routes, and the time course of their plasma concentrations was determined by HPLC analysis of the parent compounds. HBPG was completely absorbed by the ip route, and the plasma concentration could be prolonged by use of suspension formulations. HBPG is a candidate for animal trials of the ability of TK inhibitors to prevent recurrent herpes virus infections.