methyl 5,5-dimethyl-4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrobenzo[h]quinazoline-8-carboxylate | 1428432-33-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: methyl 5,5-dimethyl-4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrobenzo[h]quinazoline-8-carboxylate
• CAS: 1428432-33-0
• 化学式: C₁₆H₁₆N₂O₃S
• 分子量: 316.381
• InChiKey: WHUOHBZUSUWVBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.72
• 重原子数：
  22.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  74.95
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl 5,5-dimethyl-4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrobenzo[h]quinazoline-8-carboxylate 在 甲醇 、 sodium methylate 、 caesium carbonate 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.5h， 生成 3-allyl-2-((2-methoxyethyl)thio)-5,5-dimethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazoline-8-carboxylic acid
  参考文献：
  名称：

  Novel inhibitors of bacterial virulence: Development of 5,6-dihydrobenzo[h]quinazolin-4(3H)-ones for the inhibition of group A streptococcal streptokinase expression

  摘要：

  Resistance to antibiotics is an increasingly dire threat to human health that warrants the development of new modes of treating infection. We recently identified 1 (CCG-2979) as an inhibitor of the expression of streptokinase, a critical virulence factor in Group A Streptococcus that endows blood-borne bacteria with fibrinolytic capabilities. In this report, we describe the synthesis and biological evaluation of a series of novel 5,6-dihydrobenzo[h]quinazolin-4(3H)-one analogs of 1 undertaken with the goal of improving the modest potency of the lead. In addition to achieving an over 35-fold increase in potency, we identified structural modifications that improve the solubility and metabolic stability of the scaffold. The efficacy of two new compounds 12c (CCG-203592) and 12k (CCG-205363) against biofilm formation in Staphylococcus aureus represents a promising additional mode of action for this novel class of compounds. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.046
• 作为产物：
  描述：

  2-ethyl 6-methyl 1-amino-3,3-dimethyl-3,4-dihydronaphthalene-2,6-dicarboxylate 、 苯甲酰基异硫氰酸酯 在 potassium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 生成 methyl 5,5-dimethyl-4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrobenzo[h]quinazoline-8-carboxylate
  参考文献：
  名称：

  Novel inhibitors of bacterial virulence: Development of 5,6-dihydrobenzo[h]quinazolin-4(3H)-ones for the inhibition of group A streptococcal streptokinase expression

  摘要：

  Resistance to antibiotics is an increasingly dire threat to human health that warrants the development of new modes of treating infection. We recently identified 1 (CCG-2979) as an inhibitor of the expression of streptokinase, a critical virulence factor in Group A Streptococcus that endows blood-borne bacteria with fibrinolytic capabilities. In this report, we describe the synthesis and biological evaluation of a series of novel 5,6-dihydrobenzo[h]quinazolin-4(3H)-one analogs of 1 undertaken with the goal of improving the modest potency of the lead. In addition to achieving an over 35-fold increase in potency, we identified structural modifications that improve the solubility and metabolic stability of the scaffold. The efficacy of two new compounds 12c (CCG-203592) and 12k (CCG-205363) against biofilm formation in Staphylococcus aureus represents a promising additional mode of action for this novel class of compounds. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.046