N-(4-fluorobenzyl)-3-hydroxy-4-oxo-3,4-dihydroquinazolin-2-carboxamide | 1268706-99-5

• 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: N-(4-fluorobenzyl)-3-hydroxy-4-oxo-3,4-dihydroquinazolin-2-carboxamide
• 英文别名: N-[(4-fluorophenyl)methyl]-3-hydroxy-4-oxo-quinazoline-2-carboxamide；N-[(4-fluorophenyl)methyl]-3-hydroxy-4-oxoquinazoline-2-carboxamide
• CAS: 1268706-99-5
• 化学式: C₁₆H₁₂FN₃O₃
• 分子量: 313.288
• InChiKey: HLJHOAQPSTWWDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 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：
  82
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-amino-N-benzyloxybenzamide 在 palladium 10% on activated carbon 、 氢气 、 对甲苯磺酸 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 34.5h， 生成 N-(4-fluorobenzyl)-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

文献信息

• Synthesis of benzo-, pyrido-, thieno- and imidazo-fused N-hydroxy-4-oxopyrimidine-2-carboxylic acid derivatives
  作者：Lluís Bosch、Jean-François Mouscadet、Xio-Ju Ni、Jaume Vilarrasa

  DOI：10.1016/j.tetlet.2010.12.033

  日期：2011.2

  N-Hydroxy-4-oxoquinazoline-2-carboxamide derivatives (cyclic hydroxamic acids) and related pyrido- and thieno-substituted analogues, as well as a N-hydroxyhypoxanthine-2-carboxamide were synthesised for the first time, by means of a four-step sequence that involves a smooth reaction of aminohydroxamates with methyl trimethoxyacetate. Other strategies were unsuccessful.

  N-羟基-4-氧代喹唑啉-2-羧酰胺衍生物（环状异羟肟酸）和相关的吡啶基和噻吩基取代的类似物，以及N-羟基次黄嘌呤-2-羧酰胺是首次合成，其方法为四步步骤，涉及氨基异羟肟酸酯与三甲氧基乙酸甲酯的平稳反应。其他策略均未成功。