1-(ethoxymethyl)-5-(phenylselenyl)uracil

• 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: 1-(ethoxymethyl)-5-(phenylselenyl)uracil
• 英文别名: 1-(ethoxymethyl)-5-(phenylselenenyl)uracil；1-(Ethoxymethyl)-5-phenylselanylpyrimidine-2,4-dione
• 化学式: C₁₃H₁₄N₂O₃Se
• 分子量: 325.226
• InChiKey: PJFNWHZWZAJIND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.81
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  苯基氯化硒 、 1-(乙氧基甲基)尿嘧啶 在 吡啶 作用下， 反应 24.0h， 以74%的产率得到1-(ethoxymethyl)-5-(phenylselenyl)uracil
  参考文献：
  名称：

  Phenylselenenyl- and phenylthio-substituted pyrimidines as inhibitors of dihydrouracil dehydrogenase and uridine phosphorylase

  摘要：

  Lithiation of 5-bromo-2,4-bis (benzyloxy) pyrimidine (3) with n-BuLi at -80 degrees C followed by the addition of diphenyl diselenide or diphenyl disulfide as an electrophile furnished the corresponding 5-(phenylhetera)-2,4-bis(benzyloxy) pyrimidine, which on exposure to trimethylsilyl iodide in CH2-Cl-2 at room temperature yielded the 5-(phenylhetera)uracils in 70-75% yield. Similarly, the 6-(phenylhetera) uracils were prepared from 6-bromo-2,4-bis (benzyloxy) pyrimidine (10). 1-[(2-Hydroxyethoxy)methyl] -5-(phenylselenenyl)uracil (PSAU, 18) and 1-(ethoxymethyl)-5- (phenylselenenyl)uracil (17) were synthesized by the electrophilic addition of benzeneselenenyl chloride to the acyclic uracils under basic conditions. These compounds were evaluated for their ability to inhibit dihydrouracil dehydrogenase (DHUDase, E.C. 1.3.1.2), orotate phosphoribosyltransferase (OPRTase, E.C. 2.4.2.10), uridine phosphorylase (UrdPase, E.C. 2.4.2.3), and thymidine phosphorylase (dThdPase, E.C. 2.4.2.4). 5-(Phenylselenenyl)uracil (PSU, 6) and 5-(phenylthio)uracil (PTU, 7) inhibited DHUDase with apparent K-i values of 4.8 and 5.4 mu M, respectively. The corresponding 6-analogues, compounds 13 and 14, demonstrated inhibitory activity against OPRTase. PTU as well as PSU and its riboside, 2'-deoxyriboside, and acyclonucleosides were inhibitors of UrdPase, with PSAU (18) being the most potent with an apparent K-i value of 3.8 mu M. None of the compounds evaluated had any effect on dThdPase. Interestingly, most of the compounds showed modest selective anti-human-immunodeficiency-virus activity in acutely infected primary human lymphocytes.

  DOI：

  10.1021/jm00078a015

文献信息

• Goudgaon Naganna M., Naguib Fardos N. M., Kouni Mahmoud H. el, Schimazi R+, J. Med. Chem, 36 (1993) N 26, S 4250-4254
  作者：Goudgaon Naganna M., Naguib Fardos N. M., Kouni Mahmoud H. el, Schimazi R+

  DOI：——

  日期：——
• Phenylselenenyl- and phenylthio-substituted pyrimidines as inhibitors of dihydrouracil dehydrogenase and uridine phosphorylase
  作者：Naganna M. Goudgaon、Fardos N. M. Naguib、Mahmoud H. el Kouni、Raymond F. Schinazi

  DOI：10.1021/jm00078a015

  日期：1993.12

  Lithiation of 5-bromo-2,4-bis (benzyloxy) pyrimidine (3) with n-BuLi at -80 degrees C followed by the addition of diphenyl diselenide or diphenyl disulfide as an electrophile furnished the corresponding 5-(phenylhetera)-2,4-bis(benzyloxy) pyrimidine, which on exposure to trimethylsilyl iodide in CH2-Cl-2 at room temperature yielded the 5-(phenylhetera)uracils in 70-75% yield. Similarly, the 6-(phenylhetera) uracils were prepared from 6-bromo-2,4-bis (benzyloxy) pyrimidine (10). 1-[(2-Hydroxyethoxy)methyl] -5-(phenylselenenyl)uracil (PSAU, 18) and 1-(ethoxymethyl)-5- (phenylselenenyl)uracil (17) were synthesized by the electrophilic addition of benzeneselenenyl chloride to the acyclic uracils under basic conditions. These compounds were evaluated for their ability to inhibit dihydrouracil dehydrogenase (DHUDase, E.C. 1.3.1.2), orotate phosphoribosyltransferase (OPRTase, E.C. 2.4.2.10), uridine phosphorylase (UrdPase, E.C. 2.4.2.3), and thymidine phosphorylase (dThdPase, E.C. 2.4.2.4). 5-(Phenylselenenyl)uracil (PSU, 6) and 5-(phenylthio)uracil (PTU, 7) inhibited DHUDase with apparent K-i values of 4.8 and 5.4 mu M, respectively. The corresponding 6-analogues, compounds 13 and 14, demonstrated inhibitory activity against OPRTase. PTU as well as PSU and its riboside, 2'-deoxyriboside, and acyclonucleosides were inhibitors of UrdPase, with PSAU (18) being the most potent with an apparent K-i value of 3.8 mu M. None of the compounds evaluated had any effect on dThdPase. Interestingly, most of the compounds showed modest selective anti-human-immunodeficiency-virus activity in acutely infected primary human lymphocytes.