6-(4-Ethoxy-phenylamino)-uracil | 21333-07-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 6-(4-Ethoxy-phenylamino)-uracil
• 英文别名: 6-(4-ethoxy-anilino)-1H-pyrimidine-2,4-dione；6-[(4-ethoxyphenyl)amino]-2,4(1H,3H)-pyrimidinedione；6-(4-ethoxyanilino)-1H-pyrimidine-2,4-dione
• CAS: 21333-07-3
• 化学式: C₁₂H₁₃N₃O₃
• 分子量: 247.254
• InChiKey: PRGVUPISDNOLIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  79.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6-氯尿嘧啶 、 对乙氧基苯胺 以 水 为溶剂， 生成 6-(4-Ethoxy-phenylamino)-uracil
  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