5-苄基-1-(2-羟基乙氧基甲基)尿嘧啶 | 82857-69-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 5-苄基-1-(2-羟基乙氧基甲基)尿嘧啶
• 中文别名: (3aS,4R,7R,7aR)-9,9-二甲基-3-甲亚基-2-羰基八氢-3a,7-乙基桥茚-4-羧酸
• 英文名称: 5-Benzylacyclouridine
• 英文别名: 5-benzyl-1-(2-hydroxyethoxymethyl)uracil；benzylacyclouridine；5-benzyl-1-(2-hydroxyethoxymethyl)pyrimidine-2,4-dione
• CAS: 82857-69-0
• 化学式: C₁₄H₁₆N₂O₄
• 分子量: 276.292
• InChiKey: SPJAGILXQBHHSZ-UHFFFAOYSA-N

物化性质

• 熔点：
  144-145 °C(Solv: ethanol (64-17-5))
• 密度：
  1.290±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO：100 mg/mL（361.94 mM；需要超声）

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  丁二酸酐 、 5-苄基-1-(2-羟基乙氧基甲基)尿嘧啶 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以58%的产率得到5-benzyl-1-<(2-(3-carboxypropionyloxy)ethoxy)methyl>uracil
  参考文献：
  名称：

  5-苄基环尿苷和5-苄氧基苄基环尿苷的变体的合成

  摘要：

  合成了尿嘧啶磷酸化酶的有效抑制剂BAU（5-苄基环尿苷）和BBAU（5-苄氧基苄基-氯尿苷）的多种变体和衍生物，以评估其作为潜在的癌症化学治疗剂的能力。（“ Acyclo” ＝ 2'-羟基甲氧基甲基-）。这些包括在N-1处的亚甲基的修饰，无环基团的末端羟基的酯和在尿嘧啶碱基的5位的苄基链的延伸。BBBAU是细胞培养中非常好的FUdR增强剂。

  DOI：

  10.1002/jhet.5570230609
• 作为产物：
  描述：

  5-苄基-2-硫氧代-2,3-二氢嘧啶-4(1h)-酮 在 氨 、 溶剂黄146 、 牛血清白蛋白 、 氯乙酸 作用下， 以 甲醇 为溶剂， 反应 54.58h， 生成 5-苄基-1-(2-羟基乙氧基甲基)尿嘧啶
  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

• USE OF 6-HYDROXY-2-PYRIDONES AND DERIVATIVES THEREOF FOR PREPARING A PHARMACEUTICAL COMPOSITION THAT ACTS BY INHIBITING THE HUMAN URIDINE PHOSPHORYLASE ENZYME
  申请人：UNIÃO BRASILEIRA DE EDUCAÇAO E ASSISTÊNCIA- MANTENEDORA DA PUCRS

  公开号：EP3042657A1

  公开（公告）日：2016-07-13

  The present invention describes the use of at least one compound of formula I or II or pharmaceutically acceptable salts thereof, for preparing a pharmaceutical composition that acts by inhibiting the phosphorylase uridine enzyme. Specifically, the present invention comprises the use of the said compounds for preparing a pharmaceutical composition that acts by inhibiting the human phosphorylase uridine enzyme, which can be optionally used in combination with at least one antineoplastic, wherein said inhibition increases the effectiveness of antineoplastic and decreases the side effects caused by the administration of antineoplastics.

  本发明描述了至少一种式 I 或式 II 化合物或其药学上可接受的盐用于制备通过抑制磷酸化酶尿苷酶发挥作用的药物组合物。具体地说，本发明包括使用上述化合物制备一种通过抑制人磷酸化酶尿苷酶而起作用的药物组合物，该组合物可选择与至少一种抗肿瘤药联合使用，其中所述抑制作用可提高抗肿瘤药的疗效并减少服用抗肿瘤药引起的副作用。
• Inhibition of Uridine Phosphorylase. Synthesis and Structure−Activity Relationships of Aryl-Substituted 1-((2-Hydroxyethoxy)methyl)-5-(3-phenoxybenzyl)uracil
  作者：G. Faye Orr、David L. Musso、James L. Kelley、Suzanne S. Joyner、Stephen T. Davis、David P. Baccanari

  DOI：10.1021/jm960688j

  日期：1997.4.1

  Structure-activity relationship studies on a series of 1-((2-hydroxyethoxy)methyl)-5-(3(substituted-phenoxy)benzyl)uracils as inhibitors of murine liver uridine phosphorylase have led to compounds with IC(50)s as low as 1.4 nM. The two most potent compounds, 10j (3-cyanophenoxy) and 11f (3-chlorophenoxy) were tested in vivo for effects on steady-state concentrations of circulating uridine in mice and rats. Both compounds were substantially more efficacious than BAU (5-benzylacyclouridine) both in vitro and in vivo.
• N-Phosphonylmethoxyalkyl derivatives of pyrimidine and purine bases, methods for their preparation and pharmaceutical compositions therefrom with antiviral activity
  申请人：Ceskoslovenska akademie ved

  公开号：EP0253412B1

  公开（公告）日：1990-10-31
• Lin, Tai-Shun; Liu, Mao-Chin, Synthetic Communications, 1988, vol. 18, # 9, p. 931 - 936
  作者：Lin, Tai-Shun、Liu, Mao-Chin

  DOI：——

  日期：——
• LIN, TAI-SHUN;LIU, MAO-CHIN, SYNTH. COMMUN., 18,(1988) N 9, 931-936
  作者：LIN, TAI-SHUN、LIU, MAO-CHIN

  DOI：——

  日期：——