methyl (2S,4R)-4-(7-methoxy-2-phenylquinolin-4-yl)oxypyrrolidine-2-carboxylate | 737750-26-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: methyl (2S,4R)-4-(7-methoxy-2-phenylquinolin-4-yl)oxypyrrolidine-2-carboxylate
• CAS: 737750-26-4
• 化学式: C₂₂H₂₂N₂O₄
• 分子量: 378.428
• InChiKey: NJGKFGUOSAWCOR-UZLBHIALSA-N

物化性质

• 沸点：
  523.8±50.0 °C(Predicted)
• 密度：
  1.226±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  69.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (2S,4R)-4-(7-methoxy-2-phenylquinolin-4-yl)oxypyrrolidine-2-carboxylate 在 盐酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 1,4-二氧六环 为溶剂， 生成
  参考文献：
  名称：

  A Systematic Approach to the Optimization of Substrate-Based Inhibitors of the Hepatitis C Virus NS3 Protease:  Discovery of Potent and Specific Tripeptide Inhibitors

  摘要：

  The inadequate efficacy and tolerability of current therapies for the infectious liver disease caused by the hepatitis C virus have warranted significant efforts in the development of new therapeutics. We have previously reported competitive peptide inhibitors of the NS3 serine protease based on the N-terminal cleavage products of peptide substrates. A detailed study of the interactions of these substrate-based inhibitors with the different subsites of the serine protease active site led to the discovery of novel residues that increased the affinity of the inhibitors. In this paper, we report the combination of the best binding residues in a tetrapeptide series that resulted in extremely potent inhibitors that bind exquisitely well to this enzyme. A substantial increase in potency was obtained with the simultaneous introduction of a 7-methoxy-2-phenyl-4-quinolinoxy moiety at the gamma-position of the P2 proline and a tert-leucine as a P3 residue. The increase in potency allowed for the further truncation and led to the identification of tripeptide inhibitors. Structure activity relationship studies on this inhibitor series led to the identification of carbamate-containing tripeptides that are able to inhibit replication of subgenomic HCV RNA in cell culture with potencies below 1 muM. This inhibitor series has the potential of becoming antiviral agents for the treatment of HCV infections.

  DOI：

  10.1021/jm0494523
• 作为产物：
  描述：

  N-Boc-顺式-4-羟基-L-脯氨酸甲酯 在 盐酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 1,4-二氧六环 为溶剂， 生成 methyl (2S,4R)-4-(7-methoxy-2-phenylquinolin-4-yl)oxypyrrolidine-2-carboxylate
  参考文献：
  名称：

  A Systematic Approach to the Optimization of Substrate-Based Inhibitors of the Hepatitis C Virus NS3 Protease:  Discovery of Potent and Specific Tripeptide Inhibitors

  摘要：

  The inadequate efficacy and tolerability of current therapies for the infectious liver disease caused by the hepatitis C virus have warranted significant efforts in the development of new therapeutics. We have previously reported competitive peptide inhibitors of the NS3 serine protease based on the N-terminal cleavage products of peptide substrates. A detailed study of the interactions of these substrate-based inhibitors with the different subsites of the serine protease active site led to the discovery of novel residues that increased the affinity of the inhibitors. In this paper, we report the combination of the best binding residues in a tetrapeptide series that resulted in extremely potent inhibitors that bind exquisitely well to this enzyme. A substantial increase in potency was obtained with the simultaneous introduction of a 7-methoxy-2-phenyl-4-quinolinoxy moiety at the gamma-position of the P2 proline and a tert-leucine as a P3 residue. The increase in potency allowed for the further truncation and led to the identification of tripeptide inhibitors. Structure activity relationship studies on this inhibitor series led to the identification of carbamate-containing tripeptides that are able to inhibit replication of subgenomic HCV RNA in cell culture with potencies below 1 muM. This inhibitor series has the potential of becoming antiviral agents for the treatment of HCV infections.

  DOI：

  10.1021/jm0494523

文献信息

• TERTIARY AMINE SUBSTITUTED PEPTIDES USEFUL AS INHIBITORS OF HCV REPLICATION
  申请人：Agarwal Atul

  公开号：US20100292219A1

  公开（公告）日：2010-11-18

  The present invention provides tertiary amine substituted peptides of Formula (I) useful as inhibitors of HCV replication. The variables R and R 1 -R 12 in Formula I are described herein. The invention also includes methods for preparing such compounds. The present invention further includes pharmaceutical compositions containing tertiary amine substituted peptides and methods for using such compounds, including methods for using the compounds to treat hepatitis C infection.

  本发明提供了一种用于抑制HCV复制的三胺取代肽的公式(I)。公式I中的变量R和R1-R12在本文中有描述。该发明还包括制备这些化合物的方法。本发明进一步包括含有三胺取代肽的药物组合物以及使用这些化合物的方法，包括使用这些化合物治疗丙型肝炎感染的方法。
• HCV NS-3 serine protease inhibitors
  申请人：Tibotec Pharmaceuticals Ltd.

  公开号：EP1881002A1

  公开（公告）日：2008-01-23

  HCV inhibitors, compositions comprising these compounds as active ingredient, as well as processes for preparing these compounds, of formula: wherein A is

  HCV抑制剂，包含这些化合物作为活性成分的组合物，以及制备这些化合物的方法，其化学式为：其中A是
• [EN] ANTIVIRAL COMPOUNDS<br/>[FR] COMPOSÉS ANTIVIRAUX
  申请人：GILEAD SCIENCES INC

  公开号：WO2006020276A3

  公开（公告）日：2006-10-05
• [EN] ANTIVIRAL PHOSPHINATE COMPOUNDS<br/>[FR] COMPOSÉS ANTIVIRAUX DE PHOSPHINATE
  申请人：GILEAD SCIENCES INC

  公开号：WO2008005565A9

  公开（公告）日：2009-01-29
• US8435984B2
  申请人：——

  公开号：US8435984B2

  公开（公告）日：2013-05-07