5-(4-methyl-benzyl)-1H-pyrimidine-2,4-dione | 54512-94-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-(4-methyl-benzyl)-1H-pyrimidine-2,4-dione
• 英文别名: 5-(4'-Methylbenzyl)-uracil；5-(4-Methyl-benzyl)-1H-pyrimidine-2,4-dione；5-[(4-methylphenyl)methyl]-1H-pyrimidine-2,4-dione
• CAS: 54512-94-6
• 化学式: C₁₂H₁₂N₂O₂
• 分子量: 216.239
• InChiKey: PIDBIWZWSMEFET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-甲基苯丙酸乙酯 在 盐酸 、 sodium 、 溶剂黄146 、 氯乙酸 作用下， 反应 18.0h， 生成 5-(4-methyl-benzyl)-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Inhibition of uridine phosphorylase: synthesis and structure-activity relationships of aryl-substituted 5-benzyluracils and 1-[(2-hydroxyethoxy)methyl]-5-benzyluracils.

  摘要：

  A series of 1-[(2-hydroxyethoxy)methyl]-5-benzyluracils were synthesized and tested for inhibition of murine liver uridine phosphorylase (UrdPase). Inhibitors of UrdPase are reported to enhance the chemotherapeutic utility of 5-fluoro-2'-deoxyuridine and 5-fluorouracil and to ameliorate zidovudine-induced anemia in animal models. We prepared a series of 5-aryl-substituted analogues of 5-benzylacyclouridine (BAU), a good inhibitor of UrdPase (IC50 of 0.46 mu M), to develop a compound with enhanced potency and improved pharmacokinetics. The first phase of structure-activity relationship studies on a series of 32 aryl-substituted 5-benzyluracils found several 5-(3-alkoxybenzyl) analogues of 5-benzyluracil with enhanced potency. The acyclovir side chain, the (2-hydroxyethoxy)methyl group, was substituted on the more potent aryl-substituted 5-benzyluracils. The two most potent compounds, 10y (3-propoxy) and 10dd (3-sec-butoxy), were inhibitors of UrdPase with IC(50)s of 0.047 and 0.027 mu M, respectively. Six compounds were tested in vivo for effects on steady-state concentrations of circulating uridine in rats. Plasma uridine levels were elevated 3-9-fold by compound levels that ranged from 8 to 50 mu M.

  DOI：

  10.1021/jm00019a015

文献信息

• US6440965B1
  申请人：——

  公开号：US6440965B1

  公开（公告）日：2002-08-27
• Inhibition of uridine phosphorylase: synthesis and structure-activity relationships of aryl-substituted 5-benzyluracils and 1-[(2-hydroxyethoxy)methyl]-5-benzyluracils.
  作者：G. Faye Orr、David L. Musso、G. Evan Boswell、James L. Kelley、Suzanne S. Joyner、Stephen T. Davis、David P. Baccanari

  DOI：10.1021/jm00019a015

  日期：1995.9

  A series of 1-[(2-hydroxyethoxy)methyl]-5-benzyluracils were synthesized and tested for inhibition of murine liver uridine phosphorylase (UrdPase). Inhibitors of UrdPase are reported to enhance the chemotherapeutic utility of 5-fluoro-2'-deoxyuridine and 5-fluorouracil and to ameliorate zidovudine-induced anemia in animal models. We prepared a series of 5-aryl-substituted analogues of 5-benzylacyclouridine (BAU), a good inhibitor of UrdPase (IC50 of 0.46 mu M), to develop a compound with enhanced potency and improved pharmacokinetics. The first phase of structure-activity relationship studies on a series of 32 aryl-substituted 5-benzyluracils found several 5-(3-alkoxybenzyl) analogues of 5-benzyluracil with enhanced potency. The acyclovir side chain, the (2-hydroxyethoxy)methyl group, was substituted on the more potent aryl-substituted 5-benzyluracils. The two most potent compounds, 10y (3-propoxy) and 10dd (3-sec-butoxy), were inhibitors of UrdPase with IC(50)s of 0.047 and 0.027 mu M, respectively. Six compounds were tested in vivo for effects on steady-state concentrations of circulating uridine in rats. Plasma uridine levels were elevated 3-9-fold by compound levels that ranged from 8 to 50 mu M.