N-(2-amino-5,6,7,8-tetrahydroquinazolin-6-yl)-4-bromo-1H-pyrrole-2-carboxamide

• 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: N-(2-amino-5,6,7,8-tetrahydroquinazolin-6-yl)-4-bromo-1H-pyrrole-2-carboxamide
• 化学式: C₁₃H₁₄BrN₅O
• 分子量: 336.191
• InChiKey: BLVUHBPPOCCSKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  96.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(4-溴-1H-吡咯-2-基)-2,2,2-三氯-1-乙酮 、 (+/-)-5,6,7,8-tetrahydro-2,6-quinazolinediamine 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.75h， 以49%的产率得到N-(2-amino-5,6,7,8-tetrahydroquinazolin-6-yl)-4-bromo-1H-pyrrole-2-carboxamide
  参考文献：
  名称：

  Discovery of 4,5,6,7-Tetrahydrobenzo[1,2-d]thiazoles as Novel DNA Gyrase Inhibitors Targeting the ATP-Binding Site

  摘要：

  Bacterial DNA gyrase and topoisomerase IV are essential enzymes that control the topological state of DNA during replication and validated antibacterial drug targets. Starting from a library of marine alkaloid oroidin analogues, we identified low micromolar inhibitors of Escherichia coil DNA gyrase based on the 5,6,7,8-tetrahydroquinazoline and 4,5,6,7-tetrahydrobenzo [1,2-d]thiazole scaffolds. Structure-based optimization of the initial hits resulted in low nanomolar E. coil DNA gyrase inhibitors, some of which exhibited micromolar inhibition of E. coil topoisomerase IV and of Staphylococcus aureus homologues. Some of the compounds possessed modest antibacterial activity against Gram positive bacterial strains, while their evaluation against wild-type, impA and Delta tolC E. coil strains suggests that they are efflux pump substrates and/or do not possess the physicochemical properties necessary for cell wall penetration. Our study provides a rationale for optimization of this class of compounds toward balanced dual DNA gyrase and topoisomerase IV inhibitors with antibacterial activity.

  DOI：

  10.1021/acs.jmedchem.5b00489

文献信息

• Discovery of 4,5,6,7-Tetrahydrobenzo[1,2-<i>d</i>]thiazoles as Novel DNA Gyrase Inhibitors Targeting the ATP-Binding Site
  作者：Tihomir Tomašič、Sotirios Katsamakas、Žiga Hodnik、Janez Ilaš、Matjaž Brvar、Tom Solmajer、Sofia Montalvão、Päivi Tammela、Mihailo Banjanac、Gabrijela Ergović、Marko Anderluh、Lucija Peterlin Mašič、Danijel Kikelj

  DOI：10.1021/acs.jmedchem.5b00489

  日期：2015.7.23

  Bacterial DNA gyrase and topoisomerase IV are essential enzymes that control the topological state of DNA during replication and validated antibacterial drug targets. Starting from a library of marine alkaloid oroidin analogues, we identified low micromolar inhibitors of Escherichia coil DNA gyrase based on the 5,6,7,8-tetrahydroquinazoline and 4,5,6,7-tetrahydrobenzo [1,2-d]thiazole scaffolds. Structure-based optimization of the initial hits resulted in low nanomolar E. coil DNA gyrase inhibitors, some of which exhibited micromolar inhibition of E. coil topoisomerase IV and of Staphylococcus aureus homologues. Some of the compounds possessed modest antibacterial activity against Gram positive bacterial strains, while their evaluation against wild-type, impA and Delta tolC E. coil strains suggests that they are efflux pump substrates and/or do not possess the physicochemical properties necessary for cell wall penetration. Our study provides a rationale for optimization of this class of compounds toward balanced dual DNA gyrase and topoisomerase IV inhibitors with antibacterial activity.