6-(4-phenyl-butylamino)-1H-pyrimidine-2,4-dione | 28484-82-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-(4-phenyl-butylamino)-1H-pyrimidine-2,4-dione
• 英文别名: 6-(4-phenylbutylamino)-1H-pyrimidine-2,4-dione
• CAS: 28484-82-4
• 化学式: C₁₄H₁₇N₃O₂
• 分子量: 259.308
• InChiKey: XSLOANVLFKOGRT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 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：
  70.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(4-phenyl-butylamino)-1H-pyrimidine-2,4-dione 在 N-氯代丁二酰亚胺 作用下， 以 溶剂黄146 为溶剂， 反应 2.5h， 以50%的产率得到5-Chloro-6-(4-phenyl-butylamino)-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  人胸苷磷酸化酶的新型非底物抑制剂，其为肿瘤依赖性血管生成的潜在靶标。

  摘要：

  胸苷磷酸化酶/血小板源性内皮细胞生长因子（TP / PD-ECGF）是一种参与胸苷代谢和体内稳态的酶，其催化活性似乎在血管生成中起重要作用。在这里，我们描述了带有组氨酸标签的人TP / PD-ECGF的克隆和表达及其尿嘧啶和胸腺嘧啶类似物的测定。我们目前的设计，合成和新型的6-（苯基烷基氨基）尿嘧啶衍生物的生物评估，在微摩尔浓度，抑制人TP的分解代谢和合成代谢反应。这些碱基类似物不会被酶转化为核苷形式，因此代表了该酶的纯非底物抑制剂。

  DOI：

  10.1021/jm000037u
• 作为产物：
  描述：

  6-氯尿嘧啶 、 苯基-4-丁胺 以 水 为溶剂， 生成 6-(4-phenyl-butylamino)-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Novel 6-substituted uracil analogs as inhibitors of the angiogenic actions of thymidine phosphorylase11Abbreviations: AEAC, 6-(2-aminoethyl)amino-5-chlorouracil; CIMU, 5-chloro-6-(1-imidazolyl-methyl) uracil; FGF, fibroblast growth factor; HUVEC, human umbilical vein endothelial cell(s); PD-ECGF, platelet-derived endothelial cell growth factor; PNP, purine nucleoside phosphorylase; TGF, transforming growth factor; TNF-α, tumor necrosis factor-α; TP, thymidine phosphorylase; UP, uridine phosphorylase; and VEGF, vascular endothelial growth factor.

  摘要：

  Thymidine phosphorylase (TP) catalyzes the reversible phosphorolysis of thymidine and other pyrimidine 2'-deoxyribonucleosides. In addition, TP has been shown to possess angiogenic activity in a number of in vitro and in vivo assays, and its angiogenic activity has been linked to its catalytic activity. A series of 5- and 6-substituted uracil derivatives were synthesized and evaluated for their abilities to inhibit TP activity. Among the most active compounds was a 6-amino-substituted uracil analog, 6-(2-aminoethyl)amino-5-chlorouracil (AEAC), which was a competitive inhibitor with a K-i of 165 nM. The inhibitory activity of AEAC was selective for TP, as it did not inhibit purine nucleoside phosphorylase or uridine phosphorylase at concentrations up to 1 mM. Human recombinant TP induced human umbilical vein endothelial cell (HUVEC) migration in a modified Boyden chamber assay in vitro, and this action could be abrogated by the TP inhibitors. The actions of the inhibitors were specific for TP, as they had no effect on the chemotactic actions of vascular endothelial growth factor (VEGF). HUVEC migration was also induced when TP-transfected human colon and breast carcinoma cells were co-cultured in the Boyden chamber assay in place of the purified angiogenic factors, and a TP inhibitor blocked the tumor cell-mediated migration almost completely. These studies suggest that inhibitors of TP may be useful in pathological conditions that are dependent upon TP-driven angiogenesis. (C) 2001 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0006-2952(01)00783-3

文献信息

• Novel 6-substituted uracil analogs as inhibitors of the angiogenic actions of thymidine phosphorylase11Abbreviations: AEAC, 6-(2-aminoethyl)amino-5-chlorouracil; CIMU, 5-chloro-6-(1-imidazolyl-methyl) uracil; FGF, fibroblast growth factor; HUVEC, human umbilical vein endothelial cell(s); PD-ECGF, platelet-derived endothelial cell growth factor; PNP, purine nucleoside phosphorylase; TGF, transforming growth factor; TNF-α, tumor necrosis factor-α; TP, thymidine phosphorylase; UP, uridine phosphorylase; and VEGF, vascular endothelial growth factor.
  作者：Robert S. Klein、Michelle Lenzi、Timothy H. Lim、Kylie A. Hotchkiss、Phyllis Wilson、Edward L. Schwartz

  DOI：10.1016/s0006-2952(01)00783-3

  日期：2001.11

  Thymidine phosphorylase (TP) catalyzes the reversible phosphorolysis of thymidine and other pyrimidine 2'-deoxyribonucleosides. In addition, TP has been shown to possess angiogenic activity in a number of in vitro and in vivo assays, and its angiogenic activity has been linked to its catalytic activity. A series of 5- and 6-substituted uracil derivatives were synthesized and evaluated for their abilities to inhibit TP activity. Among the most active compounds was a 6-amino-substituted uracil analog, 6-(2-aminoethyl)amino-5-chlorouracil (AEAC), which was a competitive inhibitor with a K-i of 165 nM. The inhibitory activity of AEAC was selective for TP, as it did not inhibit purine nucleoside phosphorylase or uridine phosphorylase at concentrations up to 1 mM. Human recombinant TP induced human umbilical vein endothelial cell (HUVEC) migration in a modified Boyden chamber assay in vitro, and this action could be abrogated by the TP inhibitors. The actions of the inhibitors were specific for TP, as they had no effect on the chemotactic actions of vascular endothelial growth factor (VEGF). HUVEC migration was also induced when TP-transfected human colon and breast carcinoma cells were co-cultured in the Boyden chamber assay in place of the purified angiogenic factors, and a TP inhibitor blocked the tumor cell-mediated migration almost completely. These studies suggest that inhibitors of TP may be useful in pathological conditions that are dependent upon TP-driven angiogenesis. (C) 2001 Elsevier Science Inc. All rights reserved.
• Novel Nonsubstrate Inhibitors of Human Thymidine Phosphorylase, a Potential Target for Tumor-Dependent Angiogenesis
  作者：Federico Focher、Daniela Ubiali、Massimo Pregnolato、Chengxin Zhi、Joseph Gambino、George E. Wright、Silvio Spadari

  DOI：10.1021/jm000037u

  日期：2000.6.1

  is an enzyme involved in thymidine metabolism and homeostasis, and its catalytic activity appears to play an important role in angiogenesis. Here we describe the cloning and expression of a His-tagged human TP/PD-ECGF and its assay with uracil and thymine analogues. We present the design, synthesis, and biological evaluation of novel 6-(phenylalkylamino)uracil derivatives which, at micromolar concentrations

  胸苷磷酸化酶/血小板源性内皮细胞生长因子（TP / PD-ECGF）是一种参与胸苷代谢和体内稳态的酶，其催化活性似乎在血管生成中起重要作用。在这里，我们描述了带有组氨酸标签的人TP / PD-ECGF的克隆和表达及其尿嘧啶和胸腺嘧啶类似物的测定。我们目前的设计，合成和新型的6-（苯基烷基氨基）尿嘧啶衍生物的生物评估，在微摩尔浓度，抑制人TP的分解代谢和合成代谢反应。这些碱基类似物不会被酶转化为核苷形式，因此代表了该酶的纯非底物抑制剂。