N-(3,5-dibromo-2-hydroxybenzyl)-2-nitrobenzamide | 1276560-35-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3,5-dibromo-2-hydroxybenzyl)-2-nitrobenzamide
• CAS: 1276560-35-0
• 化学式: C₁₄H₁₀Br₂N₂O₄
• 分子量: 430.052
• InChiKey: LQDJFBSCENTVCO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.76
• 重原子数：
  22.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  92.47
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-(3,5-dibromo-2-hydroxybenzyl)-2-nitrobenzamide 、 2-氯苯甲酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 13.0h， 以50%的产率得到2,4-dibromo-6-((2-nitrobenzamido)methyl)phenyl 2-chlorobenzoate
  参考文献：
  名称：

  Synthesis and Molecular Modeling Provide Insight into a Pseudomonas aeruginosa Quorum Sensing Conundrum

  摘要：

  The triphenyl amide/ester 12 was originally reported to be a potent mimic of the natural 3-oxo-dodecanoyl homoserine lactone quorum sensing molecule in Pseudomonas aeruginosa. However, explicit synthesis/chemical characterization was lacking, and a later report providing protein crystallographic data inferred 12 to be incorrect, with 9 now being the surmised structure. Because of these inconsistencies and our interest in quorum sensing molecules utilized by Gram-negative bacteria, we found it necessary to synthesize 9 and 12 to test for agonistic activity in a P. aeruginosa reporter assay. Despite distinct regiochemical differences, both 9 and 12 were found to have comparable EC(50) values. To reconcile these unanticipated findings, modeling studies were conducted, and both compounds were revealed to have comparable properties for binding to the LasR receptor.

  DOI：

  10.1021/ja111138y
• 作为产物：
  描述：

  N-(3,5-dibromo-2-(methoxymethoxy)benzyl)-2-nitrobenzamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以61%的产率得到N-(3,5-dibromo-2-hydroxybenzyl)-2-nitrobenzamide
  参考文献：
  名称：

  Synthesis and Molecular Modeling Provide Insight into a Pseudomonas aeruginosa Quorum Sensing Conundrum

  摘要：

  The triphenyl amide/ester 12 was originally reported to be a potent mimic of the natural 3-oxo-dodecanoyl homoserine lactone quorum sensing molecule in Pseudomonas aeruginosa. However, explicit synthesis/chemical characterization was lacking, and a later report providing protein crystallographic data inferred 12 to be incorrect, with 9 now being the surmised structure. Because of these inconsistencies and our interest in quorum sensing molecules utilized by Gram-negative bacteria, we found it necessary to synthesize 9 and 12 to test for agonistic activity in a P. aeruginosa reporter assay. Despite distinct regiochemical differences, both 9 and 12 were found to have comparable EC(50) values. To reconcile these unanticipated findings, modeling studies were conducted, and both compounds were revealed to have comparable properties for binding to the LasR receptor.

  DOI：

  10.1021/ja111138y

文献信息

• Potent Irreversible Inhibitors of LasR Quorum Sensing in <i>Pseudomonas aeruginosa</i>
  作者：Kevin T. O’Brien、Joseph G. Noto、Luke Nichols-O’Neill、Lark J. Perez

  DOI：10.1021/ml500459f

  日期：2015.2.12

  Antagonism of quorum sensing represents a promising new antivirulence approach for the treatment of bacterial infection. The development of a novel series of non-natural irreversible antagonists of P. aeruginosa LasR is described. The lead compounds identified (25 and 28) display potent LasR antagonist activity and inhibit expression of the P. aeruginosa virulence factors pyocyanin and biofilm formation

  群体感应的拮抗作用代表了一种有前途的新型抗病毒治疗细菌感染的方法。描述了铜绿假单胞菌LasR的一系列新的非天然不可逆拮抗剂的开发。鉴定出的先导化合物（25和28）显示出强效的LasR拮抗剂活性，并抑制铜绿假单胞菌毒力因子Pyocyanin的表达以及PAO1和PA14中生物膜的形成。
• Development of a novel series of non-natural triaryl agonists and antagonists of the Pseudomonas aeruginosa LasR quorum sensing receptor
  作者：Joseph N. Capilato、Shane V. Philippi、Thomas Reardon、Ashleigh McConnell、Dylan C. Oliver、Amy Warren、Jill S. Adams、Chun Wu、Lark J. Perez

  DOI：10.1016/j.bmc.2016.10.021

  日期：2017.1

  sensing (QS), plays a central role in infection in numerous bacterial pathogens. Quorum sensing in Pseudomonas aeruginosa employs a series of small molecule receptors including the master QS regulator, LasR. In this study we investigate a non-natural triaryl series of LasR ligands using a combination of structure activity relationship studies and computational modeling. These studies have enabled the identification

  通过称为群体感应（QS）的过程，细菌化学通讯在众多细菌病原体的感染中起着核心作用。铜绿假单胞菌中的群体感应使用一系列小分子受体，包括主要QS调节剂LasR。在这项研究中，我们使用结构活性关系研究和计算模型相结合的方法研究了LasR配体的非天然三芳基系列。这些研究使得能够鉴定配体结合的关键结构要求，并揭示了诱导LasR的治疗相关拮抗作用的新策略。