(3R)-7-(naphthalen-1-ylmethyl)-5-oxo-8-phenyl-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester | 341027-36-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3R)-7-(naphthalen-1-ylmethyl)-5-oxo-8-phenyl-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester
• 英文别名: (3R)-7-naphthalen-1-ylmethyl-5-oxo-8-phenyl-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester；methyl (3R)-7-(naphthalen-1-ylmethyl)-5-oxo-8-phenyl-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridine-3-carboxylate
• CAS: 341027-36-9
• 化学式: C₂₆H₂₁NO₃S
• 分子量: 427.524
• InChiKey: AHFNGELQOJXHEO-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  71.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R)-7-(naphthalen-1-ylmethyl)-5-oxo-8-phenyl-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester 在 溴 、 溶剂黄146 作用下， 反应 0.17h， 以93%的产率得到(3R)-6-bromo-7-(naphthalen-1-ylmethyl)-5-oxo-8-phenyl-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester
  参考文献：
  名称：

  微波辅助合成高度取代的氨基甲基化2-吡啶酮

  摘要：

  通过采用微波辅助有机合成（MAOS），已经建立了将氨基亚甲基取代基引入高度取代的双环2-吡啶酮的有效条件。经由氰基卤代反应引​​入伯氨基亚甲基取代基，然后硼烷二甲基硫醚还原得到的腈。在这两种转化中，微波辐射均证明优于传统条件，且伯胺的总收率良好（三步法收率为55-58％）。为了在2-吡啶酮骨架中引入叔氨基亚甲基取代基，使用预制的亚胺盐的微波辅助曼尼希反应被证明是有效的。因此，以48-93％的产率获得了高度取代的2-吡啶酮。

  DOI：

  10.1021/jo048554y
• 作为产物：
  描述：

  1-萘乙酸 在 盐酸 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 0.8h， 生成 (3R)-7-(naphthalen-1-ylmethyl)-5-oxo-8-phenyl-2,3-dihydro-5H-thiazolo[3,2-a]pyridine-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Microwave-assisted decarboxylation of bicyclic 2-pyridone scaffolds and identification of Aβ-peptide aggregation inhibitors

  摘要：

  开发了一种无试剂的微波辅助去羧化程序，用于羧酸功能化的双环2-吡啶酮。该新方法基于在N-甲基吡咯烷酮（NMP）中以220°C加热600秒，证明实用且非常高效，产生的去羧化2-吡啶酮几乎定量。去羧化产品和羧酸甲酯及羧酸形式的中间体2-吡啶酮被筛选以研究其对Aβ肽聚集的影响。在本研究中描述的21种2-吡啶酮中，有两种抑制了阿尔茨海默病Aβ(1–40)肽的淀粉样蛋白形成。即使在2-吡啶酮与单体Aβ肽的比率为4:1时，仍观察到了这种效果。

  DOI：

  10.1039/b503294f

文献信息

• Regioselective Halogenations and Subsequent Suzuki−Miyaura Coupling onto Bicyclic 2-Pyridones
  作者：Christoffer Bengtsson、Fredrik Almqvist

  DOI：10.1021/jo902458g

  日期：2010.2.5

  A selective synthesis of 6-bromo-8-iodo dihydro thiazolo ring-fused 2-pyridones is described. These halogenated 2-pyridones are selectively arylated by sequential Suzuki−Miyaura couplings. This approach can advantageously be used to synthesize focused libraries of substituted ring-fused 2-pyridones, a class of compounds with novel antibacterial properties.

  描述了6-溴-8-碘二氢噻唑环稠合的2-吡啶酮的选择性合成。这些卤化的2-吡啶酮通过顺序的Suzuki-Miyaura偶联选择性地芳基化。该方法可以有利地用于合成取代的环稠合的2-吡啶酮的聚焦库，取代的环稠合的2-吡啶酮是一类具有新型抗菌特性的化合物。
• Carboxylic acid isosteres improve the activity of ring-fused 2-pyridones that inhibit pilus biogenesis in E. coli
  作者：Veronica Åberg、Pralay Das、Erik Chorell、Mattias Hedenström、Jerome S. Pinkner、Scott J. Hultgren、Fredrik Almqvist

  DOI：10.1016/j.bmcl.2008.05.020

  日期：2008.6

  compounds that inhibit pilus assembly in uropathogenic Escherichia coli. Their biological activity is clearly dependent upon a carboxylic acid functionality. Here, we present the synthesis and biological evaluation of carboxylic acid isosteres, including, for example, tetrazoles, acyl sulfonamides, and hydroxamic acids of two lead 2-pyridones. Two independent biological evaluations show that acyl sulfonamides

  环稠合 2-吡啶酮，称为 pilicides，是一种小的合成化合物，可抑制尿路致病性大肠杆菌中的菌毛组装。它们的生物活性显然取决于羧酸官能度。在这里，我们介绍了羧酸等排体的合成和生物学评价，包括例如四唑、酰基磺酰胺和两种铅 2-吡啶酮的异羟肟酸。两项独立的生物学评估表明，酰基磺酰胺和四唑显着提高了对尿路致病性大肠杆菌的杀毛虫活性。
• Synthesis of Three-Dimensional Ring Fused Heterocycles by a Selective [4 + 2] Cycloaddition Between Bicyclic Thiazolo 2-Pyridones and Arynes
  作者：Souvik Sarkar、Pardeep Singh、Simon Edin、Ola F. Wendt、Fredrik Almqvist

  DOI：10.1021/acs.joc.3c01957

  日期：2024.1.5

  A selective [4 + 2] cycloaddition reaction of thiazolo-2-pyridones with arynes has been demonstrated. The developed protocol allows rapid access to highly functionalized, structurally complex thiazolo-fused bridged isoquinolones in high yields, which are susceptible to further late-stage functionalization.

  噻唑并-2-吡啶酮与芳烃的选择性[4 + 2]环加成反应已被证明。所开发的方案允许以高产率快速获得高度功能化、结构复杂的噻唑稠合桥异喹诺酮，这些化合物容易受到进一步后期功能化的影响。
• An Enantioselective Ketene−Imine Cycloaddition Method for Synthesis of Substituted Ring-Fused 2-Pyridinones
  作者：Hans Emtenäs、Lisa Alderin、Fredrik Almqvist

  DOI：10.1021/jo015794u

  日期：2001.10.1

  Previously, a method for the stereoselective synthesis of P-lactams, starting from 2H-Delta (2)-thiazolines and Meldrum's acid derivatives, has been reported from our laboratory. We now report a new method for the synthesis of optically active, highly substituted ring-fused 2-pyridinones. This was discovered when 2-alkyl-Delta (2)-thiazolines and Meldrum's acid derivatives were treated with HCl(g) in benzene at 5 --> 78 degreesC. Further refinement of the synthetic protocol revealed that use of 1,2-dichloroethane as solvent at 0 --> 64 degreesC led to the desired 2-pyridinones;in good yields and with excellent enantioselectivity. Use of these conditions allowed preparation of 2-pyridinones from several different Delta (2)-thiazolines and Meldrum's acid derivatives and may be a general route to 2-pyridinones.
• Design, synthesis and evaluation of peptidomimetics based on substituted bicyclic 2-pyridones—Targeting virulence of uropathogenic E. coli
  作者：Veronica Åberg、Magnus Sellstedt、Mattias Hedenström、Jerome S. Pinkner、Scott J. Hultgren、Fredrik Almqvist

  DOI：10.1016/j.bmc.2006.07.017

  日期：2006.11

  Substituted bicyclic 2-pyridones, termed pilicides, are dipeptide mimetics that prevent pilus assembly in uropathogenic Escherichia coli. Here, we apply rational design to produce four classes of extended peptidomimetics based on two bioactive 2-pyridones. The key intermediate in the synthesis was an amino-functionalised 2-pyridone scaffold, which could be obtained via a mild and selective nitration and subsequent reduction. Procedures were then developed to further derivatize this amino-substituted core and a total of 24 extended peptidomimetics were synthesised and evaluated for chaperone affinity and in vivo antivirulence activity in P pili producing E coli. Enhanced affinities for the target protein were observed within the generated set of compounds, while the ability to prevent pilus assembly in vivo was significantly decreased compared to the parent lead compounds. The results suggest that the limited in vivo potencies of the analogues are either uptake/distribution related or due to loss in binding specificity. (c) 2006 Elsevier Ltd. All rights reserved.