5,5-dimethyl-2-thioxo-2,3,5,6-tetrahydrobenzo[h]quinazolin-4(1H)-one | 303101-99-7

• 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: 5,5-dimethyl-2-thioxo-2,3,5,6-tetrahydrobenzo[h]quinazolin-4(1H)-one
• 英文别名: 5,5-Dimethyl-2-sulfanylidene-1,6-dihydrobenzo[h]quinazolin-4-one
• CAS: 303101-99-7
• 化学式: C₁₄H₁₄N₂OS
• mdl: MFCD00442738
• 分子量: 258.344
• InChiKey: XMYDQZMDMBKIEW-UHFFFAOYSA-N

物化性质

• 溶解度：
  30.1 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  73.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5,5-dimethyl-2-thioxo-2,3,5,6-tetrahydrobenzo[h]quinazolin-4(1H)-one 在 lithium carbonate 、 potassium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 63.5h， 生成 2-(2-methoxyethylsulfanyl)-4-[2-(4-methoxyphenyl)ethoxy]-5,5-dimethyl-6H-benzo[h]quinazoline 、 2-(2-methoxyethylsulfanyl)-3-[2-(4-methoxyphenyl)ethyl]-5,5-dimethyl-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：

  苯甲酰基异硫氰酸酯 、 ethyl 1-amino-3,3-dimethyl-3,4-dihydronaphthalene-2-carboxylate 在 potassium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 以83%的产率得到5,5-dimethyl-2-thioxo-2,3,5,6-tetrahydrobenzo[h]quinazolin-4(1H)-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

• METHODS AND COMPOSITIONS FOR TREATING BACTERIAL INFECTION
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：US20150132352A1

  公开（公告）日：2015-05-14

  The present invention relates to chemical compounds, methods for their discovery, and their therapeutic and research use. In particular, the present invention provides compounds as therapeutic agents against bacterial infections (e.g., biofilms).

  本发明涉及化学化合物，它们的发现方法，以及它们的治疗和研究用途。具体而言，本发明提供了作为治疗剂抗击细菌感染（例如生物膜）的化合物。
• Methods and compositions for treating bacterial infection
  申请人：Curators of the University of Missouri

  公开号：US10441588B2

  公开（公告）日：2019-10-15

  The present disclosure relates to chemical compounds, methods for their discovery, and their therapeutic and research use. In particular, the present disclosure provides compounds as therapeutic agents against bacterial infections (e.g., biofilms). The present disclosure also provides topical formulations for use in methods for treating bacterial infections.

  本公开涉及化合物、发现化合物的方法及其治疗和研究用途。特别是，本公开内容提供了作为治疗剂的化合物，用于对抗细菌感染（如生物膜）。本公开还提供了用于治疗细菌感染方法的局部制剂。
• [EN] METHODS AND COMPOSITIONS FOR TREATING BACTERIAL INFECTION<br/>[FR] PROCÉDÉS ET COMPOSITIONS POUR TRAITER UNE INFECTION BACTÉRIENNE
  申请人：UNIV MICHIGAN

  公开号：WO2013166282A3

  公开（公告）日：2014-01-23
• US9504688B2
  申请人：——

  公开号：US9504688B2

  公开（公告）日：2016-11-29
• US9814719B2
  申请人：——

  公开号：US9814719B2

  公开（公告）日：2017-11-14