2-((tert-butoxycarbonyl)amino)-2-(4-((6-methoxy-2-phenylpyrimidin-4-yl)oxy)-3-vinylphenyl)acetic acid | 1450789-66-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 2-((tert-butoxycarbonyl)amino)-2-(4-((6-methoxy-2-phenylpyrimidin-4-yl)oxy)-3-vinylphenyl)acetic acid
• CAS: 1450789-66-8
• 化学式: C₂₆H₂₇N₃O₆
• 分子量: 477.517
• InChiKey: PTXLKBVYKLJNQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.24
• 重原子数：
  35.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  119.87
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  2-((tert-butoxycarbonyl)amino)-2-(4-((6-methoxy-2-phenylpyrimidin-4-yl)oxy)-3-vinylphenyl)acetic acid 在 盐酸 、 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 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-(1-(4-((6-methoxy-2-phenylpyrimidin-4-yl)oxy)-3-vinylphenyl)-2-oxo-2-((3-(((4-(trifluoromethyl)phenyl)sulfonyl)carbamoyl)phenyl)amino)ethyl)picolinamide
  参考文献：
  名称：

  Novel Peptidomimetic Hepatitis C Virus NS3/4A Protease Inhibitors Spanning the P2–P1′ Region

  摘要：

  Herein, novel hepatitis C virus NS3/4A protease inhibitors based on a P2 pyrimidinyloxyphenylglycine in combination with various regioisomers of an aryl acyl sulfonamide functionality in P1 are presented. The P1' 4-(trifluoromethyl)phenyl side chain was shown to be particularly beneficial in terms of inhibitory potency. Several inhibitors with K i-values in the nanomolar range were developed and included identification of promising P3-truncated inhibitors spanning from P2-P1'. Of several different P2 capping groups that were evaluated, a preference for the sterically congested Boc group was revealed. The inhibitors were found to retain inhibitory potencies for A156T, D168V, and R155K variants of the protease. Furthermore, in vitro pharmacokinetic profiling showed several beneficial effects on metabolic stability as well as on apparent intestinal permeability from both P3 truncation and the use of the P1' 4-(trifluoromethyl)phenyl side chain.

  DOI：

  10.1021/ml400217r
• 作为产物：
  描述：

  4-氯-6-甲氧基-2-苯基嘧啶 在 potassium tert-butylate 、 palladium diacetate 、 potassium carbonate 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 乙二醇二甲醚 、 水 、 二甲基亚砜 为溶剂， 反应 48.25h， 生成 2-((tert-butoxycarbonyl)amino)-2-(4-((6-methoxy-2-phenylpyrimidin-4-yl)oxy)-3-vinylphenyl)acetic acid
  参考文献：
  名称：

  Novel Peptidomimetic Hepatitis C Virus NS3/4A Protease Inhibitors Spanning the P2–P1′ Region

  摘要：

  Herein, novel hepatitis C virus NS3/4A protease inhibitors based on a P2 pyrimidinyloxyphenylglycine in combination with various regioisomers of an aryl acyl sulfonamide functionality in P1 are presented. The P1' 4-(trifluoromethyl)phenyl side chain was shown to be particularly beneficial in terms of inhibitory potency. Several inhibitors with K i-values in the nanomolar range were developed and included identification of promising P3-truncated inhibitors spanning from P2-P1'. Of several different P2 capping groups that were evaluated, a preference for the sterically congested Boc group was revealed. The inhibitors were found to retain inhibitory potencies for A156T, D168V, and R155K variants of the protease. Furthermore, in vitro pharmacokinetic profiling showed several beneficial effects on metabolic stability as well as on apparent intestinal permeability from both P3 truncation and the use of the P1' 4-(trifluoromethyl)phenyl side chain.

  DOI：

  10.1021/ml400217r