5-(3-苄氧基苄基)-1-(2'-羟基乙氧基甲基)尿嘧啶 | 82857-75-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 5-(3-苄氧基苄基)-1-(2'-羟基乙氧基甲基)尿嘧啶
• 中文别名: 2-甲基-6-(苯基乙炔基)吡啶
• 英文名称: 5-(benzyloxybenzyl)acyclouridine
• 英文别名: 1-((2-Hydroxyethoxy)methyl)-5-(3-(benzyloxy)benzyl)pyrimidine-2,4(1H,3H)-dione；1-(2-hydroxyethoxymethyl)-5-[(3-phenylmethoxyphenyl)methyl]pyrimidine-2,4-dione
• CAS: 82857-75-8
• 化学式: C₂₁H₂₂N₂O₅
• 分子量: 382.416
• InChiKey: CSXNPJKDZKLDET-UHFFFAOYSA-N

物化性质

• 密度：
  1.279±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  5-(3-苄氧基苄基)-1-(2'-羟基乙氧基甲基)尿嘧啶 在 palladium on activated charcoal 氢气 作用下， 生成 5-(3-hydroxybenzyl)-1-<(2-hydroxyethoxy)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：

  3-邻羟基苯基丙酸乙酯 在 氨 、 potassium carbonate 、 溶剂黄146 、 牛血清白蛋白 、 氯乙酸 、 lithium diisopropyl amide 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 54.58h， 生成 5-(3-苄氧基苄基)-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

• 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.
• REGULATED BIOCIRCUIT SYSTEMS
  申请人：Obsidian Therapeutics, Inc.

  公开号：US20190192691A1

  公开（公告）日：2019-06-27

  The present invention provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities.
• IDENTIFICATION AND TARGETED MODULATION OF GENE SIGNALING NETWORKS
  申请人：CAMP4 THERAPEUTICS CORPORATION

  公开号：US20210254056A1

  公开（公告）日：2021-08-19

  The present invention provides methods and compositions for the evaluation, alteration and/or optimization of gene signaling. Methods and systems are also provided which exploit the information generated in the identification of new targets and non-canonical signaling pathways.
• 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.
• Synthesis of variants of 5-benzylacyclouridine and 5-benzyloxybenzylacyclouridine
  作者：Shih-Hsi Chu、Zhi-Hao Chen、Zum-Yao Weng、Elizabeth C. Rowe、Edward Chu、Ming-Yu Wang Chu

  DOI：10.1002/jhet.5570230609

  日期：1986.11

  A number of variations and derivatives of BAU (5-benzylacyclouridine) and BBAU (5-benzyloxybenzylacy-clouridine), potent inhibitors of uridine phosphorylase were synthesized for evaluation as potential cancer chemotherapeutic agents. (“Acyclo” = 2′-hydroxymethoxymethyl-). These included a modification of the methylene group at N-1, esters of the terminal hydroxyl of the acyclo group, and extension

  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。