(3R)-7-((7-methoxy-2-oxo-2H-chromen-4-yl)methyl)-5-oxo-8-(thiophen-2-yl)-3,5-dihydro-2H-thiazolo[3,2-a]pyridine-3-carboxylic acid | 1374967-43-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: (3R)-7-((7-methoxy-2-oxo-2H-chromen-4-yl)methyl)-5-oxo-8-(thiophen-2-yl)-3,5-dihydro-2H-thiazolo[3,2-a]pyridine-3-carboxylic acid
• 英文别名: (3R)-7-[(7-methoxy-2-oxochromen-4-yl)methyl]-5-oxo-8-thiophen-2-yl-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridine-3-carboxylic acid
• CAS: 1374967-43-7
• 化学式: C₂₃H₁₇NO₆S₂
• 分子量: 467.523
• InChiKey: YCMCDWFCBAOUPG-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  147
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-噻吩乙腈 在 盐酸 、 水 、 三乙胺 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 0.03h， 生成 (3R)-7-((7-methoxy-2-oxo-2H-chromen-4-yl)methyl)-5-oxo-8-(thiophen-2-yl)-3,5-dihydro-2H-thiazolo[3,2-a]pyridine-3-carboxylic acid
  参考文献：
  名称：

  Mapping pilicide anti-virulence effect in Escherichia coli, a comprehensive structure–activity study

  摘要：

  Pilicides prevent pili formation and thereby the development of bacterial biofilms in Escherichia coli. We have performed a comprehensive structure activity relationship (SAR) study of the dihydrothiazolo ring-fused 2-pyridone pilicide central fragment by varying all open positions. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) was used to distinguish active from inactive compounds in which polarity proved to be the most important factor for discrimination. A quantitative SAR (QSAR) partial least squares (PLS) model was calculated on the active compounds for prediction of biofilm inhibition activity. In this model, compounds with high inhibitory activity were generally larger, more lipophilic, more flexible and had a lower HOMO. Overall, this resulted in both highly valuable SAR information and potent inhibitors of type 1 pili dependent biofilm formation. The most potent biofilm inhibitor had an EC50 of 400 nM. (C) 2012 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2012.01.048

文献信息

• Design and Synthesis of Fluorescent Pilicides and Curlicides: Bioactive Tools to Study Bacterial Virulence Mechanisms
  作者：Erik Chorell-、Jerome S. Pinkner、Christoffer Bengtsson、Sofie Edvinsson、Corinne K. Cusumano、Erik Rosenbaum、Lennart B. Å. Johansson、Scott J. Hultgren、Fredrik Almqvist

  DOI：10.1002/chem.201103936

  日期：2012.4.10

  Pilicides and curlicides are compounds that block the formation of the virulence factors pili and curli, respectively. To facilitate studies of the interaction between these compounds and the pili and curli assembly systems, fluorescent pilicides and curlicides have been synthesized. This was achieved by using a strategy based on structure–activity knowledge, in which key pilicide and curlicide substituents

  Pilicides 和 curlicides 是分别阻止毒力因子 pili 和 curli 形成的化合物。为了促进对这些化合物与菌毛和卷曲组装系统之间相互作用的研究，已经合成了荧光 pilicides 和 curlicides。这是通过使用基于结构-活性知识的策略来实现的，其中环稠合二氢噻唑并 2-吡啶酮中心片段上的关键 pilicide 和 curlicide 取代基被荧光团取代。在依赖菌毛和卷曲的生物膜测定中测量到的几种荧光化合物的活性有所提高。我们通过引入香豆素和 4,4-difluoro-4-bora-3a,4a-diaza- s创建了荧光 pilicides 和 curlicides- 茚(BODIPY) 荧光团位于拟肽 pilicide 和 curlicide 中心片段的两个位置。在这些化合物存在下生长的尿路致病性大肠杆菌(UPEC) 菌株 UTI89 的荧光图像表明，这些化合物与具有异质分布的细菌密切相关。
• Mapping pilicide anti-virulence effect in Escherichia coli, a comprehensive structure–activity study
  作者：Erik Chorell、Jerome S. Pinkner、Christoffer Bengtsson、Thomas Sainte-Luce Banchelin、Sofie Edvinsson、Anna Linusson、Scott J. Hultgren、Fredrik Almqvist

  DOI：10.1016/j.bmc.2012.01.048

  日期：2012.5

  Pilicides prevent pili formation and thereby the development of bacterial biofilms in Escherichia coli. We have performed a comprehensive structure activity relationship (SAR) study of the dihydrothiazolo ring-fused 2-pyridone pilicide central fragment by varying all open positions. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) was used to distinguish active from inactive compounds in which polarity proved to be the most important factor for discrimination. A quantitative SAR (QSAR) partial least squares (PLS) model was calculated on the active compounds for prediction of biofilm inhibition activity. In this model, compounds with high inhibitory activity were generally larger, more lipophilic, more flexible and had a lower HOMO. Overall, this resulted in both highly valuable SAR information and potent inhibitors of type 1 pili dependent biofilm formation. The most potent biofilm inhibitor had an EC50 of 400 nM. (C) 2012 Published by Elsevier Ltd.