4-(1-Isobutyl-6-naphthalen-1-ylmethyl-2,4-dioxo-1,2,4,6-tetrahydro-pyrrolo[3,4-d]pyrimidin-3-yl)-butyric acid ethyl ester | 166755-28-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-(1-Isobutyl-6-naphthalen-1-ylmethyl-2,4-dioxo-1,2,4,6-tetrahydro-pyrrolo[3,4-d]pyrimidin-3-yl)-butyric acid ethyl ester
• CAS: 166755-28-8
• 化学式: C₂₇H₃₁N₃O₄
• 分子量: 461.561
• InChiKey: STHZELXOXUFSHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.17
• 重原子数：
  34.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  75.23
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  4-(1-Isobutyl-6-naphthalen-1-ylmethyl-2,4-dioxo-1,2,4,6-tetrahydro-pyrrolo[3,4-d]pyrimidin-3-yl)-butyric acid ethyl ester 在 lithium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 20.0h， 以0.5 g的产率得到4-(1-Isobutyl-6-naphthalen-1-ylmethyl-2,4-dioxo-1,2,4,6-tetrahydro-pyrrolo[3,4-d]pyrimidin-3-yl)-butyric acid
  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 甲酸 、 TEA 、 溴 、 potassium carbonate 作用下， 以 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.25h， 生成 4-(1-Isobutyl-6-naphthalen-1-ylmethyl-2,4-dioxo-1,2,4,6-tetrahydro-pyrrolo[3,4-d]pyrimidin-3-yl)-butyric acid ethyl ester
  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