(3R)-7-((naphthalen-1-yloxy)methyl)-5-oxo-8-(thiophen-2-yl)-3,5-dihydro-2H-thiazolo[3,2-a]pyridine-3-carboxylic acid | 1374967-45-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (3R)-7-((naphthalen-1-yloxy)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-(naphthalen-1-yloxymethyl)-5-oxo-8-thiophen-2-yl-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridine-3-carboxylic acid
• CAS: 1374967-45-9
• 化学式: C₂₃H₁₇NO₄S₂
• 分子量: 435.524
• InChiKey: PJXSSYWWJRDYOZ-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  6

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-((naphthalen-1-yloxy)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

• [EN] COMPOUNDS AND METHODS FOR TREATMENT OF CHLAMYDIA INFECTIONS<br/>[FR] COMPOSÉS ET MÉTHODES POUR LE TRAITEMENT D'INFECTIONS À CHLAMYDIA
  申请人：QURETECH BIO AB

  公开号：WO2014185853A1

  公开（公告）日：2014-11-20

  The present invention provides new compounds, pharmaceutical compositions and methods for the treatment and diagnosis of Chlamydia infections. The compounds are substituted ring-fused 2-pyridones and are shown to reduce the infectivity of Chlamydia. The invention further identifies the membrane-localized hexose-phosphate permease (UhpC)of Chlamydia as drug target and provides methods for the identification and development of new anti-Chlamydia compounds

  本发明提供了用于治疗和诊断沙眼感染的新化合物、药物组合物和方法。这些化合物是取代环融合的2-吡啶酮，并且已被证明可以减少沙眼的传染性。该发明进一步确定了沙眼的膜定位己糖磷酸透过酶（UhpC）作为药物靶标，并提供了用于识别和开发新的抗沙眼化合物的方法。
• 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.