3-ethyl-5,5-dimethyl-2-thioxo-2,3,5,6-tetrahydrobenzo[h]quinazolin-4(1H)-one | 337496-59-0

• 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: 3-ethyl-5,5-dimethyl-2-thioxo-2,3,5,6-tetrahydrobenzo[h]quinazolin-4(1H)-one
• 英文别名: 3-Ethyl-5,5-dimethyl-2-sulfanylidene-1,6-dihydrobenzo[h]quinazolin-4-one
• CAS: 337496-59-0
• 化学式: C₁₆H₁₈N₂OS
• mdl: MFCD01807058
• 分子量: 286.398
• InChiKey: HRNWUCRQFANYOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-ethyl-5,5-dimethyl-2-thioxo-2,3,5,6-tetrahydrobenzo[h]quinazolin-4(1H)-one 、 2-(chloromethyl)-5,5-dimethyl-5,6-dihydrobenzo[h]quinazolin-4(3H)-one 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 10.0h， 以86%的产率得到2-{[(5,5-dimethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolin-2-yl)methyl]sulfanyl}-3-ethyl-5,5-dimethyl-5,6-dihydrobenzo[h]quinazolin-4(3H)-one
  参考文献：
  名称：

  2-（氯甲基）-5,5-二甲基-5,6-二氢苯并[h]喹唑啉-4（3 H）-one的一些转化

  摘要：

  1-氨基-3,3-二甲基-3,4-二氢萘-2-甲腈与氯乙酰氯的缩合得到氯N-（2-氰基-3,3-二甲基-3,4-二氢萘-1-基乙酰胺，将其环化成2-（氯甲基）-5,5-二甲基-5,6-二氢苯并[ h ]喹唑啉-4（3 H）-。后者与各种亲核试剂（碱金属醇盐，哌嗪，2-硫烷基乙醇）反应，得到2-（烷氧基甲基）-，2-（哌嗪-1-基甲基）-和2-{[（（2-羟乙基）硫烷基]甲基} -5,5-二甲基-5,6-二氢苯并[ h ]喹唑啉-4（3 H）-ones。2-（氯甲基）苯并[ h ]喹唑啉与喹唑啉和苯并[ h ]的2-巯基衍生物的缩合]喹唑啉导致形成双喹唑啉，其中5,5-二甲基-5,6-二氢苯并[ h ]喹唑啉-4（3 H）-一个片段通过CH连接到喹唑啉或苯并[ h ]喹唑啉系统2 S桥。

  DOI：

  10.1134/s1070428018040152
• 作为产物：
  描述：

  邻甲基苯腈 在 lithium diisopropyl amide 作用下， 以 乙醇 、 正己烷 、 二乙二醇二甲醚 为溶剂， 反应 22.75h， 生成 3-ethyl-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

• 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.
• Some Transformations of 2-(Chloromethyl)-5,5-dimethyl-5,6-dihydrobenzo[h]quinazolin-4(3H)-one
  作者：A. I. Markosyan、K. K. Hayrapetyan、S. H. Gabrielyan、V. Z. Shirinyan、S. S. Mamyan、J. A. Avakimyan、G. M. Stepanyan

  DOI：10.1134/s1070428018040152

  日期：2018.4

  ide which underwent cyclization to 2-(chloromethyl)-5,5-dimethyl-5,6-dihydrobenzo[h]quinazolin-4(3H)-one. The latter reacted with various nucleophiles (alkali metal alkoxides, piperazine, 2-sulfanylethanol) to give 2-(alkoxymethyl)-, 2-(piperazin-1-ylmethyl)-, and 2-[(2-hydroxyethyl)sulfanyl]methyl}-5,5-dimethyl-5,6-dihydrobenzo[h]quinazolin- 4(3H)-ones. The condensation of 2-(chloromethyl)benzo[h]quinazoline

  1-氨基-3,3-二甲基-3,4-二氢萘-2-甲腈与氯乙酰氯的缩合得到氯N-（2-氰基-3,3-二甲基-3,4-二氢萘-1-基乙酰胺，将其环化成2-（氯甲基）-5,5-二甲基-5,6-二氢苯并[ h ]喹唑啉-4（3 H）-。后者与各种亲核试剂（碱金属醇盐，哌嗪，2-硫烷基乙醇）反应，得到2-（烷氧基甲基）-，2-（哌嗪-1-基甲基）-和2-[（（2-羟乙基）硫烷基]甲基} -5,5-二甲基-5,6-二氢苯并[ h ]喹唑啉-4（3 H）-ones。2-（氯甲基）苯并[ h ]喹唑啉与喹唑啉和苯并[ h ]的2-巯基衍生物的缩合]喹唑啉导致形成双喹唑啉，其中5,5-二甲基-5,6-二氢苯并[ h ]喹唑啉-4（3 H）-一个片段通过CH连接到喹唑啉或苯并[ h ]喹唑啉系统2 S桥。