6-(p-methoxyphenyl)-4-methylthio-2-oxo-2H-pyran-3-carboxylic acid | 115411-57-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 6-(p-methoxyphenyl)-4-methylthio-2-oxo-2H-pyran-3-carboxylic acid
• 英文别名: 6-(4-Methoxyphenyl)-4-methylsulfanyl-2-oxopyran-3-carboxylic acid
• CAS: 115411-57-9
• 化学式: C₁₄H₁₂O₅S
• 分子量: 292.312
• InChiKey: SJCZTACVCURDFR-UHFFFAOYSA-N

物化性质

• 熔点：
  231 °C(Solv: methanol (67-56-1))
• 沸点：
  437.7±45.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  98.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-(p-methoxyphenyl)-4-methylthio-2-oxo-2H-pyran-3-carboxylic acid 在 盐酸羟胺 、 碳酸氢钠 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 4-(hydroxyamino)-N-(2-hydroxyethyl)-6-(4-methoxyphenyl)-2-oxo-2H-pyran-3-carboxamide
  参考文献：
  名称：

  Synthesis and Anti-HCV Activity of 4-Hydroxyamino α-Pyranone Carboxamide Analogues

  摘要：

  High genetic variability in hepatitis C virus (HCV), emergence of drug resistant viruses and side effects demand the requirement for development of new scaffolds to show an alternate mechanism. Herein, we report discovery of new scaffold I based on 4-hydroxyamino alpha-pyranone carboxamide as promising anti-HCV agents. A comprehensive structure activity relationship (SAR) was explored with several newly synthesized compounds. In all promising compounds (17-19, 21-22, 24-25, and 49) with EC50 ranging 0.15 to 0.40 mu M, the aryl group at C-6 position of alpha-pyranone were unsubstituted. In particular, 25 demonstrated potential anti-HCV activity with EC50 of 0.18 mu M in cell based HCV replicon system with lower cytotoxicity (CC50 > 20 mu M) and provided a new scaffold for anti-HCV drug development. Further investigations, including biochemical characterization, are yet to be performed to elucidate its possible mode of action.

  DOI：

  10.1021/ml400432f
• 作为产物：
  描述：

  1-(4-甲氧基苯基)-3,3-二(甲硫基)-2-丙烯-1-酮 、 丙二酸二甲酯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 以26%的产率得到6-(p-methoxyphenyl)-4-methylthio-2-oxo-2H-pyran-3-carboxylic acid
  参考文献：
  名称：

  Tominaga, Yoshinori; Ushirogochi, Atsuyuki; Matsuda, Yoshiro, Journal of Heterocyclic Chemistry, 1987, vol. 24, p. 1557 - 1567

  摘要：

  DOI：

文献信息

• <scp>Microwave‐assisted</scp> decarboxylation of <scp> 2 <i>H</i> ‐Pyran‐3‐carboxylic </scp> acid derivatives under basic condition
  作者：Uttam Kumar Mishra、Chandralata Bal

  DOI：10.1002/jhet.4559

  日期：2022.12

  Despite the availability of several methods for decarboxylation, this area remains exploratory and requires new development. Here, we report a highly efficient microwave-assisted hydrodecarboxylation of 4-(methylthio)-2-oxo-6-aryl-2H-pyran-3-carboxylic acids (1a-k) under basic condition to obtain 4-(methylthio)-6-aryl-2H-pyran-2-ones (2a-k) with >90% yield. The requirement of proton source from the

  尽管有多种脱羧方法可用，但该领域仍处于探索阶段，需要新的发展。在这里，我们报道了在碱性条件下 4-(甲硫基)-2-氧代-6-芳基-2 H-吡喃-3-羧酸 ( 1a-k ) 的高效微波辅助加氢脱羧反应，得到 4-(甲硫基) -6-aryl-2 H -pyran-2-ones ( 2a-k ) 产率 >90%。通过在CD 3 OD中进行1b和1e的反应，分别获得氘代化合物2 l和2 m，观察到溶剂对质子源的需求。所有化合物均通过光谱分析进行了表征。此外，化合物通过单晶 X 射线衍射研究分析了2b和2e 。
• Synthesis and anti-HCV determinant motif identification in pyranone carboxamide scaffold
  作者：Tuniki Balaraju、Ananda Kumar Konreddy、Afsana Parveen、Massaki Toyama、Wataru Ito、Srinivas Karampuri、Masanori Baba、Ashoke Sharon、Chandralata Bal

  DOI：10.1016/j.bmcl.2015.09.060

  日期：2015.11

  Hepatitis C Virus exhibits high genetic diversity. The current treatment for genotype-1 with similar to 80% sustained virologic responses is a combination of pegylated interferon, ribavirin and boceprevir/telaprevir/simeprevir which is associated with several side effects and need close monitoring. Therefore, novel therapies are invited for safer and more efficient treatment. This study was designed for synthesis of new alpha-pyranone carboxamide analogs for evaluation of anti-HCV activity to delineate structure-activity relationship (SAR) and to identify anti-HCV determinant motif on this new scaffold. Forty four new alpha-pyranone carboxamide analogs were synthesized. Six potential anti-HCV candidates 11a (EC50 = 0.35 mu M), 11e (EC50 = 0.48 mu M), 12f (EC50 = 0.47 mu M), 12g (EC50 = 0.39 mu M), 12h (EC50 = 0.20 mu M) and 12j (EC50 = 0.25 mu M) with lower cytotoxicity (CC50 > 20 mu M) were discovered through cell based HCV replicon system. The activity profile of forty four new a-pyranone carboxamide analogs suggests the role of an aromatic motif in the B region to add a synergistic effect to NHOH motif at 4-position and revels an anti-HCV activity determinants motif under this scaffold. The biochemical assay against most promising HCV target protein 'NS3 protease and NS5B polymerase' showed no activity and open a scope to explore new mechanism inhibitor. (C) 2015 Elsevier Ltd. All rights reserved.
• Skeletal hybridization and PfRIO-2 kinase modeling for synthesis of α-pyrone analogs as anti-malarial agent
  作者：Afsana Parveen、Arnish Chakraborty、Ananda Kumar Konreddy、Harapriya Chakravarty、Ashoke Sharon、Vishal Trivedi、Chandralata Bal

  DOI：10.1016/j.ejmech.2013.10.028

  日期：2013.12

  The pharmacophoric hybridization and computational design approach were applied to generate a novel series of alpha-pyrone analogs as plausible anti-malarial lead candidate. A putative active site in flexible loop close to wing-helix domain of PfRIO2 kinase was explored computationally to understand the molecular basis of ligand binding. All the synthesized molecules (3a-g) exhibited in vitro antimalarial activity. Oxidative stress induced by 3a-d were calculated and found to be significantly higher in case of 3b. Therefore, 3b, which shown most significant result was identified as promising lead for further SAR study to develop potent anti-malarials. (C) 2013 Elsevier Masson SAS. All rights reserved.
• TOMINAGA, YOSHINORI;USHIROGOCHI, ATSUYAKI;MATSUDA, YOSHIRO, J. HETEROCYCL. CHEM., 24,(1987) N 6, 1557-1567
  作者：TOMINAGA, YOSHINORI、USHIROGOCHI, ATSUYAKI、MATSUDA, YOSHIRO

  DOI：——

  日期：——
• Synthesis and Anti-HCV Activity of 4-Hydroxyamino α-Pyranone Carboxamide Analogues
  作者：Ananda Kumar Konreddy、Massaki Toyama、Wataru Ito、Chandralata Bal、Masanori Baba、Ashoke Sharon

  DOI：10.1021/ml400432f

  日期：2014.3.13

  High genetic variability in hepatitis C virus (HCV), emergence of drug resistant viruses and side effects demand the requirement for development of new scaffolds to show an alternate mechanism. Herein, we report discovery of new scaffold I based on 4-hydroxyamino alpha-pyranone carboxamide as promising anti-HCV agents. A comprehensive structure activity relationship (SAR) was explored with several newly synthesized compounds. In all promising compounds (17-19, 21-22, 24-25, and 49) with EC50 ranging 0.15 to 0.40 mu M, the aryl group at C-6 position of alpha-pyranone were unsubstituted. In particular, 25 demonstrated potential anti-HCV activity with EC50 of 0.18 mu M in cell based HCV replicon system with lower cytotoxicity (CC50 > 20 mu M) and provided a new scaffold for anti-HCV drug development. Further investigations, including biochemical characterization, are yet to be performed to elucidate its possible mode of action.