4-methylthio-6-phenyl-2-oxo-2H-pyran-3-carboxylic acid | 115411-37-5

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-methylthio-6-phenyl-2-oxo-2H-pyran-3-carboxylic acid
• 英文别名: 4-Methylsulfanyl-2-oxo-6-phenylpyran-3-carboxylic acid
• CAS: 115411-37-5
• 化学式: C₁₃H₁₀O₄S
• 分子量: 262.286
• InChiKey: KZBBAYSKVVEITE-UHFFFAOYSA-N

物化性质

• 熔点：
  248 °C
• 沸点：
  404.7±45.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  88.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-methylthio-6-phenyl-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)-2-oxo-N,6-diphenyl-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：

  3,3-双甲基磺酰基-1-苯丙酮 在 水 、 sodium hydride 作用下， 以 1,4-二氧六环 为溶剂， 反应 6.0h， 生成 4-methylthio-6-phenyl-2-oxo-2H-pyran-3-carboxylic acid
  参考文献：
  名称：

  基于结构的分子设计，α-吡喃酮类似物作为抗HSV药物的合成和生物学评估

  摘要：

  有几种治疗1型和2型单纯疱疹病毒的选择。然而，非特异性抑制和耐药性保证了新的抗疱疹性化合物具有更好的治疗特性或不同的作用方式的发现。HSV DNA聚合酶的非核苷抑制剂靶向的位点对于天然核苷或核苷抑制剂的结合而言并不重要。在本研究中，我们已经探索了使用基于结构的建模方法寻找基于α-吡喃酮类似物作为非核苷抑制剂的新先导分子的可能性。合成设计的分子，并使用MTT分析评估其抗HSV活性。化合物5h的EC 50 7.4μg/ ml和CC 50与阿昔洛韦相比，52.5μg/ ml对HSV具有中等活性。还进行了噬斑减少试验，结果显示5h对HSV-1更有效，选择性指数为12.8，比对HSV-2更好（SI = 3.6）。还评估了合成的化合物的抗HIV活性，但没有一个具有活性。

  DOI：

  10.1016/j.bmcl.2012.07.098

文献信息

• Anti-HSV activity and mode of action study of α-pyrone carboxamides
  作者：Srinivas Karampuri、Durbadal Ojha、Paromita Bag、Harapriya Chakravarty、Chandralata Bal、Debprasad Chattopadhyay、Ashoke Sharon

  DOI：10.1039/c4ra01303d

  日期：——

  Potential anti-HSV lead candidate3d(EC₅₀= 9.8 μg ml⁻¹) and its possible binding mode to utilize cavity-A and cavity-B of viral enzyme HSV polymerase.

  潜在的抗HSV首选候选药物3d（EC50= 9.8 μg ml-1）及其可能的结合模式，利用病毒酶HSV聚合酶的空腔A和空腔B。
• <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 。
• Amidate ion‐mediated intramolecular ring transformation of 2‐pyrones to 2‐pyridones
  作者：Rajan Kumar、Neha Kumari、Harpreet Kaur、Chandralata Bal、Ashoke Sharon

  DOI：10.1002/jhet.4671

  日期：2023.9

  2-pyrone-3-carboxamides (1) with a good yield at room temperature. The notable feature of this reaction is the promotion of amidate ion formation mediated by NaH to initiate intramolecular ring transformation. In addition to ring transformation, simultaneous decarboxylation and substitution under the metal-free condition in one pot have been achieved to yield N-substituted 2-pyridones (3) from 1.

  在此，我们报告了一种新的且具有成本效益的方法，用于从2-吡喃酮-3-甲酰胺 ( 1 ) 合成N-取代的2-吡啶酮-3-羧酸 ( 2 )，在室温下具有良好的产率。该反应的显着特点是促进 NaH 介导的酰胺离子形成，从而引发分子内环转化。除了环化之外，还实现了在无金属条件下一锅同时脱羧和取代，从1得到N-取代的2-吡啶酮( 3 ) 。
• 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.
• Tominaga, Yoshinori; Ushirogochi, Atsuyuki; Matsuda, Yoshiro, Journal of Heterocyclic Chemistry, 1987, vol. 24, p. 1557 - 1567
  作者：Tominaga, Yoshinori、Ushirogochi, Atsuyuki、Matsuda, Yoshiro

  DOI：——

  日期：——