4-(2-hydroxyethylamino)-N-(2-hydroxyphenyl)-2-oxo-6-phenyl-2H-pyran-3-carboxamide

• 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: 4-(2-hydroxyethylamino)-N-(2-hydroxyphenyl)-2-oxo-6-phenyl-2H-pyran-3-carboxamide
• 英文别名: 4-(2-hydroxyethylamino)-N-(2-hydroxyphenyl)-2-oxo-6-phenylpyran-3-carboxamide
• 化学式: C₂₀H₁₈N₂O₅
• 分子量: 366.373
• InChiKey: AJEOHOIRAJDGQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  108
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3,3-双甲基磺酰基-1-苯丙酮 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 4-(2-hydroxyethylamino)-N-(2-hydroxyphenyl)-2-oxo-6-phenyl-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

文献信息

• [EN] NOVEL PYRANONE CARBOXAMIDE DERIVATIVE AND USE THEREOF AS ANTI-HEPATITIS C VIRUS AGENT<br/>[FR] NOUVEAU DÉRIVÉ DE PYRANONE-CARBOXAMIDE ET UTILISATION CORRESPONDANTE COMME AGENT ANTI-VIRUS D'HÉPATITE C
  申请人：UNIV KAGOSHIMA

  公开号：WO2015008779A1

  公开（公告）日：2015-01-22

  　本発明は、下記式（Ｉ）：（式中、Ａｒは置換又は無置換の芳香族基であり、Ｒは置換又は無置換の炭化水素基、又は置換又は無置換の複素環基であり、ｎは０～３の整数である。） で示される化合物、その塩又はそれらの溶媒和物、及び前記化合物を含有する抗ＨＣＶ薬に関する。
• 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.