N-benzyl-2-(2-methoxyethylsulfanyl)-5,5-dimethyl-4-oxo-3-prop-2-enyl-6H-benzo[h]quinazoline-8-carboxamide | 1428432-36-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-benzyl-2-(2-methoxyethylsulfanyl)-5,5-dimethyl-4-oxo-3-prop-2-enyl-6H-benzo[h]quinazoline-8-carboxamide
• CAS: 1428432-36-3
• 化学式: C₂₈H₃₁N₃O₃S
• 分子量: 489.638
• InChiKey: GKCRJXDXBSQSDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  96.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  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 、 1-羟基苯并三唑 、 caesium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.5h， 生成 N-benzyl-2-(2-methoxyethylsulfanyl)-5,5-dimethyl-4-oxo-3-prop-2-enyl-6H-benzo[h]quinazoline-8-carboxamide
  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

文献信息

• Novel inhibitors of bacterial virulence: Development of 5,6-dihydrobenzo[h]quinazolin-4(3H)-ones for the inhibition of group A streptococcal streptokinase expression
  作者：Bryan D. Yestrepsky、Yuanxi Xu、Meghan E. Breen、Xiaoqin Li、Walajapet G. Rajeswaran、Jenny G. Ryu、Roderick J. Sorenson、Yasuhiro Tsume、Michael W. Wilson、Wenpeng Zhang、Duxin Sun、Hongmin Sun、Scott D. Larsen

  DOI：10.1016/j.bmc.2013.01.046

  日期：2013.4

  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.