N-(2-bromoethyl)-4-(2-hydroxyethylamino)-2-oxo-6-(thiophen-2-yl)-2H-pyran-3-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: N-(2-bromoethyl)-4-(2-hydroxyethylamino)-2-oxo-6-(thiophen-2-yl)-2H-pyran-3-carboxamide
• 英文别名: N-(2-bromoethyl)-4-(2-hydroxyethylamino)-2-oxo-6-thiophen-2-ylpyran-3-carboxamide
• 化学式: C₁₄H₁₅BrN₂O₄S
• 分子量: 387.254
• InChiKey: FXXQLPSIPAXXFT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3,3-bis(methylthio)-1-(thiophen-2-yl)prop-2-en-1-one 在 2-( 1H-7-azabenzotniazol-1-yl)-1,1,3,3-tetrarmethyluroniumhexafluorophosphate methanaminium 、 sodium hydride 、 碳酸氢钠 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 N-(2-bromoethyl)-4-(2-hydroxyethylamino)-2-oxo-6-(thiophen-2-yl)-2H-pyran-3-carboxamide
  参考文献：
  名称：

  Synthesis and anti-HCV determinant motif identification in pyranone carboxamide scaffold

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2015.09.060