1-Isobutyl-6-(4-methoxy-benzyl)-3-methyl-2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidine-5-carbaldehyde | 166755-31-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 1-Isobutyl-6-(4-methoxy-benzyl)-3-methyl-2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidine-5-carbaldehyde
• 英文别名: 6-[(4-Methoxyphenyl)methyl]-3-methyl-1-(2-methylpropyl)-2,4-dioxopyrrolo[3,4-d]pyrimidine-5-carbaldehyde
• CAS: 166755-31-3
• 化学式: C₂₀H₂₃N₃O₄
• 分子量: 369.42
• InChiKey: RUBNWUCAQMFRDA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  71.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  吗啉 、 1-Isobutyl-6-(4-methoxy-benzyl)-3-methyl-2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidine-5-carbaldehyde 在 盐酸 、 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以52%的产率得到6-<(4-methoxyphenyl)methyl>-3-methyl-1-(2-methylpropyl)-5-<(4-morpholinyl)methyl>pyrrolo<3,4-d>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 RaNi sodium hydroxide 、 正丁基锂 、 甲酸 、 TEA 、 溴 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 34.25h， 生成 1-Isobutyl-6-(4-methoxy-benzyl)-3-methyl-2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidine-5-carbaldehyde
  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