6-Ethyl-1-isobutyl-3-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile | 166755-36-8

• 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: 6-Ethyl-1-isobutyl-3-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile
• 英文别名: 4-Ethyl-1-methyl-3-(2-methylpropyl)-2,6-dioxopyrimidine-5-carbonitrile
• CAS: 166755-36-8
• 化学式: C₁₂H₁₇N₃O₂
• 分子量: 235.286
• InChiKey: IXEQZCMBODRRNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  64.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-Ethyl-1-isobutyl-3-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile 在 RaNi 甲酸 作用下， 反应 0.33h， 以79%的产率得到6-ethyl-5-formyl-3-methyl-1-(2-methylpropyl)pyrimidine-2,4-dione
  参考文献：
  名称：

  Novel Inhibitors of the Nuclear Factor of Activated T Cells (NFAT)-Mediated Transcription of .beta.-Galactosidase: Potential Immunosuppressive and Antiinflammatory Agents

  摘要：

  The preparation of a series of quinazoline-2,4-diones, 1-3, and pyrrolo[3,4-d]pyrimidine-2,4-diones, 4-8 is described. A small number of quinazolinedione analogs were identified from random screening to possess low micromolar (1.3-4.4 mu M) potency in the nuclear factor of activated T cells-1-regulated beta-galactosidase expression assay. An expanded analog search resulted in identifying pyrrolopyrimidinedione 4b which is 5-10-fold (0.26 mu M) more potent than the quinazolinediones. Replacement of the benzyl group with naphthyl led to greater potency and conformationally restricted analogs 4u-w. The naphthyl and acenaphthyl analogs are 10-100 times more potent inhibitors of beta-galactosidase expression than 4b. Binding affinity data for displacement of radiolabeled 4s from Jurkat cell membranes reflected an excellent correlation with the IC50 value for inhibition of beta-galactosidase activity. These products, whose structure-activity relationships are discussed, are of interest as potential agents for preventing interleukin-2 gene transcription.

  DOI：

  10.1021/jm00014a009
• 作为产物：
  描述：

  5-cyano-6-methyl-1-(2-methylpropyl)pyrimidine-2,4-dione 在 sodium hydroxide 、 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.5h， 生成 6-Ethyl-1-isobutyl-3-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile
  参考文献：
  名称：

  Novel Inhibitors of the Nuclear Factor of Activated T Cells (NFAT)-Mediated Transcription of .beta.-Galactosidase: Potential Immunosuppressive and Antiinflammatory Agents

  摘要：

  The preparation of a series of quinazoline-2,4-diones, 1-3, and pyrrolo[3,4-d]pyrimidine-2,4-diones, 4-8 is described. A small number of quinazolinedione analogs were identified from random screening to possess low micromolar (1.3-4.4 mu M) potency in the nuclear factor of activated T cells-1-regulated beta-galactosidase expression assay. An expanded analog search resulted in identifying pyrrolopyrimidinedione 4b which is 5-10-fold (0.26 mu M) more potent than the quinazolinediones. Replacement of the benzyl group with naphthyl led to greater potency and conformationally restricted analogs 4u-w. The naphthyl and acenaphthyl analogs are 10-100 times more potent inhibitors of beta-galactosidase expression than 4b. Binding affinity data for displacement of radiolabeled 4s from Jurkat cell membranes reflected an excellent correlation with the IC50 value for inhibition of beta-galactosidase activity. These products, whose structure-activity relationships are discussed, are of interest as potential agents for preventing interleukin-2 gene transcription.

  DOI：

  10.1021/jm00014a009