(4R,6R)-4,6-bis(hydroxymethyl)-1,3-diazinan-2-one | 114155-58-7

• 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: (4R,6R)-4,6-bis(hydroxymethyl)-1,3-diazinan-2-one
• CAS: 114155-58-7
• 化学式: C₆H₁₂N₂O₃
• 分子量: 160.173
• InChiKey: KEFXIOVQCNPYHI-RFZPGFLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.59
• 重原子数：
  11.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  81.59
• 氢给体数：
  4.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  DL-2,4-二氨基戊二酸 在 氯化亚砜 、 dimethyl sulfide borane 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 25.5h， 生成 (4R,6R)-4,6-bis(hydroxymethyl)-1,3-diazinan-2-one
  参考文献：
  名称：

  cis-4-Carboxy-6-(mercaptomethyl)-3,4,5,6-tetrahydropyrimidin-2(1H)-one, a potent inhibitor of mammalian dihydroorotase

  摘要：

  A series of cis- and trans-4-carboxy-3,4,5,6-tetrahydropyrimidin-2(1H)-ones possessing either a carboxy, hydroxymethyl, or mercaptomethyl substituent at C-6 were prepared and tested for their ability to inhibit mammalian dihydroorotase. Of these compounds, only the cis-6-mercaptomethyl compound, cis-1, was found to be a potent competitive inhibitor of the enzyme (Ki = 140 nM at pH 7.4 and 8.5) when assayed in the direction of dihydro-L-orotate hydrolysis. These results suggest that the inhibition arises from the ligation of the thiolate to the zinc atom which is thought to be located in the enzyme's active site. Although analysis of cis-1 with 2,2'-dithiobis(5-nitrobenzoic acid) revealed significant loss of the free thiol group under enzymatic assay conditions, the addition of the reducing agent, dithiothreitol, to the enzymatic reaction mixtures afforded cis-1 complete protection against this chemical decomposition, as evidenced by lowering of the inhibition constant in the presence of dithiothreitol. Compound cis-1 had no significant antiproliferative activity against B16 melanoma cells in tissue culture, possibly due to the rapid decomposition of the compound or poor permeability into cells.

  DOI：

  10.1021/jm00402a018