5-(butylamino)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione

• 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: 5-(butylamino)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione
• 英文别名: 5-(Butylamino)-1,3-dimethylpyrimidine-2,4-dione
• 化学式: C₁₀H₁₇N₃O₂
• 分子量: 211.264
• InChiKey: CODQZYIYORHRKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  52.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(butylamino)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione 在 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 0.25h， 生成
  参考文献：
  名称：

  Design, synthesis of 1,3-dimethylpyrimidine-2,4-diones as potent and selective aldehyde dehydrogenase 1A1 (ALDH1A1) inhibitors with glucose consumption improving activity

  摘要：

  LDH1A1, one of 19 NAD(P)(+)-dependent aldehyde dehydrogenases, participates in multiple metabolic pathways and has been indicated to play an important role in obesity and diabetes. In this study, a series of 1,3-di-methylpyrimidine-2,4-diones were designed, synthesized and evaluated as novel selective aldehyde dehy-drogenase 1A1 inhibitors. Among them, compounds 46, 50, 53, 56 and 57 exhibited excellent inhibitory activity against ALDH1A1 with IC50 values in the low nanomolar range and high selectivity over ALDH1A2, ALDH1A3, ALDH2 and ALDH3A1. Furthermore, in vitro study demonstrated that compound 57 effectively improved glucose consumption in HepG2 cells compared to compound 1 (CM026).

  DOI：

  10.1016/j.bioorg.2020.103971
• 作为产物：
  描述：

  1,3-二甲基-5-硝基尿嘧啶水合物 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 5-(butylamino)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Design, synthesis of 1,3-dimethylpyrimidine-2,4-diones as potent and selective aldehyde dehydrogenase 1A1 (ALDH1A1) inhibitors with glucose consumption improving activity

  摘要：

  LDH1A1, one of 19 NAD(P)(+)-dependent aldehyde dehydrogenases, participates in multiple metabolic pathways and has been indicated to play an important role in obesity and diabetes. In this study, a series of 1,3-di-methylpyrimidine-2,4-diones were designed, synthesized and evaluated as novel selective aldehyde dehy-drogenase 1A1 inhibitors. Among them, compounds 46, 50, 53, 56 and 57 exhibited excellent inhibitory activity against ALDH1A1 with IC50 values in the low nanomolar range and high selectivity over ALDH1A2, ALDH1A3, ALDH2 and ALDH3A1. Furthermore, in vitro study demonstrated that compound 57 effectively improved glucose consumption in HepG2 cells compared to compound 1 (CM026).

  DOI：

  10.1016/j.bioorg.2020.103971

文献信息

• Design, synthesis of 1,3-dimethylpyrimidine-2,4-diones as potent and selective aldehyde dehydrogenase 1A1 (ALDH1A1) inhibitors with glucose consumption improving activity
  作者：Zonghui Ma、Ling Jiang、Guoxin Li、Dailin Liang、Luanfeng Li、Li Liu、Cheng Jiang

  DOI：10.1016/j.bioorg.2020.103971

  日期：2020.8

  LDH1A1, one of 19 NAD(P)(+)-dependent aldehyde dehydrogenases, participates in multiple metabolic pathways and has been indicated to play an important role in obesity and diabetes. In this study, a series of 1,3-di-methylpyrimidine-2,4-diones were designed, synthesized and evaluated as novel selective aldehyde dehy-drogenase 1A1 inhibitors. Among them, compounds 46, 50, 53, 56 and 57 exhibited excellent inhibitory activity against ALDH1A1 with IC50 values in the low nanomolar range and high selectivity over ALDH1A2, ALDH1A3, ALDH2 and ALDH3A1. Furthermore, in vitro study demonstrated that compound 57 effectively improved glucose consumption in HepG2 cells compared to compound 1 (CM026).