N-(4-bromophenyl)-4-methylsulfanyl-2-oxo-6-phenylpyran-3-carboxamide | 1403495-75-9

• 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-bromophenyl)-4-methylsulfanyl-2-oxo-6-phenylpyran-3-carboxamide
• CAS: 1403495-75-9
• 化学式: C₁₉H₁₄BrNO₃S
• 分子量: 416.295
• InChiKey: IDVOEHPFWNDBPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 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-bromophenyl)-4-methylsulfanyl-2-oxo-6-phenylpyran-3-carboxamide 在 双氧水 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 4.0h， 以40%的产率得到N-(4-bromophenyl)-4-hydroxy-2-oxo-6-phenyl-2H-pyran-3-carboxamide
  参考文献：
  名称：

  Skeletal hybridization and PfRIO-2 kinase modeling for synthesis of α-pyrone analogs as anti-malarial agent

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2013.10.028
• 作为产物：
  描述：

  3,3-双甲基磺酰基-1-苯丙酮 在 水 、 sodium hydride 、 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 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.25h， 生成 N-(4-bromophenyl)-4-methylsulfanyl-2-oxo-6-phenylpyran-3-carboxamide
  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

• 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。
• 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.