3-allyl-5,5-dimethyl-2-(methylthio)-5,6-dihydrobenzo[h]quinazolin-4(3H)-one | 369605-57-2

• 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: 3-allyl-5,5-dimethyl-2-(methylthio)-5,6-dihydrobenzo[h]quinazolin-4(3H)-one
• 英文别名: 3-Allyl-5,5-dimethyl-2-(methylsulfanyl)-5,6-dihydrobenzo[H]quinazolin-4(3H)-one；5,5-dimethyl-2-methylsulfanyl-3-prop-2-enyl-6H-benzo[h]quinazolin-4-one
• CAS: 369605-57-2
• 化学式: C₁₈H₂₀N₂OS
• mdl: MFCD01557074
• 分子量: 312.436
• InChiKey: SIDJSPOOOCKHMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  58
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-allyl-5,5-dimethyl-2-(methylthio)-5,6-dihydrobenzo[h]quinazolin-4(3H)-one 在 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 2-(ethylamino)-5,5-dimethyl-3-prop-2-enyl-6H-benzo[h]quinazolin-4-one
  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：

  邻甲基苯腈 在 potassium hydroxide 、 lithium diisopropyl amide 作用下， 以 乙醇 、 正己烷 、 二乙二醇二甲醚 为溶剂， 反应 23.25h， 生成 3-allyl-5,5-dimethyl-2-(methylthio)-5,6-dihydrobenzo[h]quinazolin-4(3H)-one
  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.