1-<(3,4-dichlorophenyl)methyl>-5,6-dimethyl-2,4(1H,3H)-pyrimidinedione | 133167-04-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-<(3,4-dichlorophenyl)methyl>-5,6-dimethyl-2,4(1H,3H)-pyrimidinedione
• 英文别名: 1-[(3,4-dichlorophenyl)methyl]-5,6-dimethylpyrimidine-2,4-dione
• CAS: 133167-04-1
• 化学式: C₁₃H₁₂Cl₂N₂O₂
• 分子量: 299.156
• InChiKey: GHPILAWOGUIQIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.51
• 重原子数：
  19.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  54.86
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1-<(3,4-dichlorophenyl)methyl>-5,6-dimethyl-2,4(1H,3H)-pyrimidinedione 在 sodium hydroxide 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 3-<(3,4-dichlorophenyl)methyl>-3,6-dihydro-4,5-dimethyl-2,6-dioxo-1(2H)-pyrimidineacetic acid
  参考文献：
  名称：

  Quinazolineacetic acids and related analogs as aldose reductase inhibitors

  摘要：

  A variety of 2,4-dioxoquinazolineacetic acids (10, 11) were synthesized as hybrids of the known aldose reductase inhibitors alrestatin (8), ICI-105,552 (9), and ICI-128,436 (2) and evaluated for their ability to inhibit partially purified bovine lens aldose reductase (in vitro) and their effectiveness to decrease galactitol accumulation in the 4-day galactosemic rat model (in vivo). In support to SAR studies, related analogues pyrimidinediones (12), dihydroquinazolones (13), and indazolidinones (14, 15) were synthesized and tested in the in vitro and in vivo assays. All prepared compounds (10-15) have shown a high level of in vitro activity (IC50 approximately 10(-6) to 4 x 10(-8) M). However, only the 2,4-quinazolinedione analogues 10 and 11, with similar N-aralkyl substitution found in 2 and 9, have exhibited good oral potency. The remaining compounds were either inactive or had only a marginal in vivo activity. The structure-activity data support the presence of a secondary hydrophobic pocket in the vicinity of the primary lipophilic region of the enzyme.

  DOI：

  10.1021/jm00108a038
• 作为产物：
  描述：

  5,6-dimethyl-2H,4H-1,3-oxazine-2,4-dione 、 3,4-二氯苄胺 以 乙醇 为溶剂， 反应 1.5h， 以25.1%的产率得到1-<(3,4-dichlorophenyl)methyl>-5,6-dimethyl-2,4(1H,3H)-pyrimidinedione
  参考文献：
  名称：

  Quinazolineacetic acids and related analogs as aldose reductase inhibitors

  摘要：

  A variety of 2,4-dioxoquinazolineacetic acids (10, 11) were synthesized as hybrids of the known aldose reductase inhibitors alrestatin (8), ICI-105,552 (9), and ICI-128,436 (2) and evaluated for their ability to inhibit partially purified bovine lens aldose reductase (in vitro) and their effectiveness to decrease galactitol accumulation in the 4-day galactosemic rat model (in vivo). In support to SAR studies, related analogues pyrimidinediones (12), dihydroquinazolones (13), and indazolidinones (14, 15) were synthesized and tested in the in vitro and in vivo assays. All prepared compounds (10-15) have shown a high level of in vitro activity (IC50 approximately 10(-6) to 4 x 10(-8) M). However, only the 2,4-quinazolinedione analogues 10 and 11, with similar N-aralkyl substitution found in 2 and 9, have exhibited good oral potency. The remaining compounds were either inactive or had only a marginal in vivo activity. The structure-activity data support the presence of a secondary hydrophobic pocket in the vicinity of the primary lipophilic region of the enzyme.

  DOI：

  10.1021/jm00108a038