N-(4-methylphenyl)-4-methylsulfanyl-2-oxo-6-phenylpyran-3-carboxamide | 1403495-77-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-methylphenyl)-4-methylsulfanyl-2-oxo-6-phenylpyran-3-carboxamide
• CAS: 1403495-77-1
• 化学式: C₂₀H₁₇NO₃S
• 分子量: 351.426
• InChiKey: XZUANKPPNDVKGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(4-methylphenyl)-4-methylsulfanyl-2-oxo-6-phenylpyran-3-carboxamide 在 盐酸羟胺 、 碳酸氢钠 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以68%的产率得到4-(hydroxyamino)-2-oxo-6-phenyl-N-p-tolyl-2H-pyran-3-carboxamide
  参考文献：
  名称：

  发现2-异恶唑-3-基-乙酰胺类似物作为具有显着抗HIV活性的热休克蛋白90（HSP90）抑制剂。

  摘要：

  最近在病毒研究中对热休克蛋白90（HSP90）的探索激增支持其作为克服当前抗病毒治疗方案的缺点的有希望的靶标的出现。在继续努力探索新型抗逆转录病毒分子的过程中，我们设计，合成了15种基于2-isoxazol-3-yl-acetamide的新型化合物（2a-o），然后分析了它们的抗HIV活性和细胞毒性研究。发现2a-b，2e，2j和2l-m在其最高非细胞毒性浓度（HNC）下具有抑制潜力> 80％的活性。这些分子的抗HIV活性的进一步特征表明2l具有比第二代HSP90抑制剂AUY922好约3.5倍的治疗指数。2l的抗HIV活性是细胞类型，病毒分离株和病毒载量独立现象。有趣的是，在HNC的无细胞体外测定系统中，与它们的已知抑制剂相比，2l不会显着调节病毒酶，例如逆转录酶（RT），整合酶（IN）和蛋白酶（PR）。此外，2l介导的对HSP90的抑制作用减弱了HIV-1 LTR驱动的基因表达。综上所述

  DOI：

  10.1016/j.ejmech.2019.111699
• 作为产物：
  描述：

  3,3-双甲基磺酰基-1-苯丙酮 在 sodium hydride 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 生成 N-(4-methylphenyl)-4-methylsulfanyl-2-oxo-6-phenylpyran-3-carboxamide
  参考文献：
  名称：

  酰胺基离子介导的 2-吡喃酮分子内环转化为 2-吡啶酮

  摘要：

  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 ) 。

  DOI：

  10.1002/jhet.4671

文献信息

• Structure based molecular design, synthesis and biological evaluation of α-pyrone analogs as anti-HSV agent
  作者：Srinivas Karampuri、Paromita Bag、Sabina Yasmin、Devendra Kumar Chouhan、Chandralata Bal、Debashis Mitra、Debprasad Chattopadhyay、Ashoke Sharon

  DOI：10.1016/j.bmcl.2012.07.098

  日期：2012.10

  natural nucleoside or nucleoside inhibitors. In the present study, we have explored the possibility to find a new lead molecule based on α-pyrone analogs as non-nucleoside inhibitors using structure based modeling approach. The designed molecules were synthesized and evaluated for anti-HSV activity using MTT assay. The compound 5h with EC50 7.4 μg/ml and CC50 52.5 μg/ml was moderately active against HSV

  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。
• Formamidine-Induced Translocative Rearrangement of 2-Pyrones to 2-Pyridone Analogues with a 1,5-Diketo Motif
  作者：Ashoke Sharon、Rajan Kumar

  DOI：10.1055/a-2017-4176

  日期：——

  A new formamidine-induced translocative rearrangement of 2-pyrone analogues into 2-pyridone derivatives with a 1,5-diketo motif was identified. All the products were characterized by spectroscopic analysis. In addition, single-crystal X-ray structural studies of two molecules were performed.

  鉴定了一种新的甲脒诱导的 2-吡喃酮类似物易位重排为具有 1,5-二酮基序的 2-吡啶酮衍生物。所有产物均通过光谱分析表征。此外，还进行了两个分子的单晶 X 射线结构研究。
• 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.
• 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.
• Discovery of 2-isoxazol-3-yl-acetamide analogues as heat shock protein 90 (HSP90) inhibitors with significant anti-HIV activity
  作者：Jay Trivedi、Afsana Parveen、Farhana Rozy、Alapani Mitra、Chandralata Bal、Debashis Mitra、Ashoke Sharon

  DOI：10.1016/j.ejmech.2019.111699

  日期：2019.12

  therapeutic index than AUY922, the second generation HSP90 inhibitor. The anti-HIV activity of 2l is a cell type, virus isolate and viral load independent phenomena. Interestingly, 2l does not significantly modulate viral enzymes like Reverse Transcriptase (RT), Integrase (IN) and Protease (PR) as compared to their known inhibitors in a cell free in vitro assay system at its HNC. Further, 2l mediated inhibition

  最近在病毒研究中对热休克蛋白90（HSP90）的探索激增支持其作为克服当前抗病毒治疗方案的缺点的有希望的靶标的出现。在继续努力探索新型抗逆转录病毒分子的过程中，我们设计，合成了15种基于2-isoxazol-3-yl-acetamide的新型化合物（2a-o），然后分析了它们的抗HIV活性和细胞毒性研究。发现2a-b，2e，2j和2l-m在其最高非细胞毒性浓度（HNC）下具有抑制潜力> 80％的活性。这些分子的抗HIV活性的进一步特征表明2l具有比第二代HSP90抑制剂AUY922好约3.5倍的治疗指数。2l的抗HIV活性是细胞类型，病毒分离株和病毒载量独立现象。有趣的是，在HNC的无细胞体外测定系统中，与它们的已知抑制剂相比，2l不会显着调节病毒酶，例如逆转录酶（RT），整合酶（IN）和蛋白酶（PR）。此外，2l介导的对HSP90的抑制作用减弱了HIV-1 LTR驱动的基因表达。综上所述