3-hydroxy-N-(4-nitrobenzyl)-4-oxo-3,4-dihydroquinazolin-2-carboxamide | 1374632-91-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3-hydroxy-N-(4-nitrobenzyl)-4-oxo-3,4-dihydroquinazolin-2-carboxamide
• 英文别名: 3-hydroxy-N-[(4-nitrophenyl)methyl]-4-oxo-quinazoline-2-carboxamide；3-hydroxy-N-[(4-nitrophenyl)methyl]-4-oxoquinazoline-2-carboxamide
• CAS: 1374632-91-3
• 化学式: C₁₆H₁₂N₄O₅
• 分子量: 340.295
• InChiKey: JACUYHGNRBIYJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-hydroxy-N-(4-nitrobenzyl)-4-oxo-3,4-dihydroquinazolin-2-carboxamide 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以23%的产率得到N-(4-aminobenzyl)-3-hydroxy-4-oxo-3,4-dihydroquinazolin-2-carboxamide
  参考文献：
  名称：

  Discovery of N-Arylalkyl-3-hydroxy-4-oxo-3,4-dihydroquinazolin-2-carboxamide Derivatives as HCV NS5B Polymerase Inhibitors

  摘要：

  AbstractThe metal ion chelating β‐N‐hydroxy‐γ‐ketocarboxamide pharmacophore was integrated into a quinazolinone scaffold, leading to N‐arylalkyl‐3‐hydroxy‐4‐oxo‐3,4‐dihydroquinazolin‐2‐carboxamide derivatives as hepatitis C virus (HCV) NS5B polymerase inhibitors. Lead optimization led to the identification of N‐phenylpropyl carboxamide 9 k (IC50=8.8 μM). Compound 9 k possesses selectivity toward HCV1b replicon Ava.5 cells (EC50=17.5 μM) over parent Huh‐7 cells (CC50=187.5 μM). Compound 9 k effects a mixed mode of NS5B inhibition, with NTP‐competitive displacement properties. The interaction between 9 k and NS5B is stabilized by the presence of magnesium ions. Docking studies showed that the binding orientation of 9 k occupies the central portions of both magnesium‐mediated and NTP‐ribose‐response binding sites within the active site region of NS5B. As a result, 3‐hydroxy‐4‐oxo‐3,4‐dihydroquinazolin‐2‐carboxamide derivatives are disclosed herein as novel, mainly active site inhibitors of HCV NS5B polymerase.

  DOI：

  10.1002/cmdc.201200058
• 作为产物：
  描述：

  2-amino-N-benzyloxybenzamide 在 palladium 10% on activated carbon 、 氢气 、 对甲苯磺酸 、 三乙胺 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 58.5h， 生成 3-hydroxy-N-(4-nitrobenzyl)-4-oxo-3,4-dihydroquinazolin-2-carboxamide
  参考文献：
  名称：

  Discovery of N-Arylalkyl-3-hydroxy-4-oxo-3,4-dihydroquinazolin-2-carboxamide Derivatives as HCV NS5B Polymerase Inhibitors

  摘要：

  AbstractThe metal ion chelating β‐N‐hydroxy‐γ‐ketocarboxamide pharmacophore was integrated into a quinazolinone scaffold, leading to N‐arylalkyl‐3‐hydroxy‐4‐oxo‐3,4‐dihydroquinazolin‐2‐carboxamide derivatives as hepatitis C virus (HCV) NS5B polymerase inhibitors. Lead optimization led to the identification of N‐phenylpropyl carboxamide 9 k (IC50=8.8 μM). Compound 9 k possesses selectivity toward HCV1b replicon Ava.5 cells (EC50=17.5 μM) over parent Huh‐7 cells (CC50=187.5 μM). Compound 9 k effects a mixed mode of NS5B inhibition, with NTP‐competitive displacement properties. The interaction between 9 k and NS5B is stabilized by the presence of magnesium ions. Docking studies showed that the binding orientation of 9 k occupies the central portions of both magnesium‐mediated and NTP‐ribose‐response binding sites within the active site region of NS5B. As a result, 3‐hydroxy‐4‐oxo‐3,4‐dihydroquinazolin‐2‐carboxamide derivatives are disclosed herein as novel, mainly active site inhibitors of HCV NS5B polymerase.

  DOI：

  10.1002/cmdc.201200058

文献信息

• Discovery of N-Arylalkyl-3-hydroxy-4-oxo-3,4-dihydroquinazolin-2-carboxamide Derivatives as HCV NS5B Polymerase Inhibitors
  作者：Ravindra Ramesh Deore、Grace Shiahuy Chen、Pei-Teh Chang、Ting-Rong Chern、Shin-Yu Lai、Ming-Hsieh Chuang、Jung-Hsin Lin、Fan-Lu Kung、Chien-Shu Chen、Chun-Tang Chiou、Ji-Wang Chern

  DOI：10.1002/cmdc.201200058

  日期：2012.5

  AbstractThe metal ion chelating β‐N‐hydroxy‐γ‐ketocarboxamide pharmacophore was integrated into a quinazolinone scaffold, leading to N‐arylalkyl‐3‐hydroxy‐4‐oxo‐3,4‐dihydroquinazolin‐2‐carboxamide derivatives as hepatitis C virus (HCV) NS5B polymerase inhibitors. Lead optimization led to the identification of N‐phenylpropyl carboxamide 9 k (IC50=8.8 μM). Compound 9 k possesses selectivity toward HCV1b replicon Ava.5 cells (EC50=17.5 μM) over parent Huh‐7 cells (CC50=187.5 μM). Compound 9 k effects a mixed mode of NS5B inhibition, with NTP‐competitive displacement properties. The interaction between 9 k and NS5B is stabilized by the presence of magnesium ions. Docking studies showed that the binding orientation of 9 k occupies the central portions of both magnesium‐mediated and NTP‐ribose‐response binding sites within the active site region of NS5B. As a result, 3‐hydroxy‐4‐oxo‐3,4‐dihydroquinazolin‐2‐carboxamide derivatives are disclosed herein as novel, mainly active site inhibitors of HCV NS5B polymerase.