3,6-dimethyl-5-formyl-1-(cyclopropylmethyl)pyrimidine-2,4-dione | 166755-06-2

• 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: 3,6-dimethyl-5-formyl-1-(cyclopropylmethyl)pyrimidine-2,4-dione
• 英文别名: 1-(Cyclopropylmethyl)-3,6-dimethyl-2,4-dioxopyrimidine-5-carbaldehyde
• CAS: 166755-06-2
• 化学式: C₁₁H₁₄N₂O₃
• 分子量: 222.244
• InChiKey: JYOOLQUNZNNNKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  57.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,6-dimethyl-5-formyl-1-(cyclopropylmethyl)pyrimidine-2,4-dione 在 TEA 、 溴 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 1.0h， 生成 1-(cyclopropylmethyl)-3-methyl-6-(1-naphthylmethyl)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-1-(cyclopropylmethyl)-3,6-dimethylpyrimidine-2,4-dione 在 RaNi 甲酸 作用下， 反应 0.25h， 生成 3,6-dimethyl-5-formyl-1-(cyclopropylmethyl)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

文献信息

• Novel Inhibitors of the Nuclear Factor of Activated T Cells (NFAT)-Mediated Transcription of .beta.-Galactosidase: Potential Immunosuppressive and Antiinflammatory Agents
  作者：William F. Michne、Joseph D. Schroeder、Joseph W. Guiles、Adi M. Treasurywala、Carolyn A. Weigelt、Mary F. Stansberry、Elizabeth McAvoy、Chandra R. Shah、Elizabeth Bump

  DOI：10.1021/jm00014a009

  日期：1995.7

  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.