methyl (6S,9S,12S)-6-(tert-butyl)-12-(2,2-difluoroethyl)-9-(4-((7-methoxy-2-phenylquinolin-4-yl)oxy)phenyl)-2,2-dimethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oate | 928162-21-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (6S,9S,12S)-6-(tert-butyl)-12-(2,2-difluoroethyl)-9-(4-((7-methoxy-2-phenylquinolin-4-yl)oxy)phenyl)-2,2-dimethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oate
• CAS: 928162-21-4
• 化学式: C₄₀H₄₆F₂N₄O₈
• 分子量: 748.824
• InChiKey: QLSKICGFTBYQTP-CHHQVBBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.11
• 重原子数：
  54.0
• 可旋转键数：
  13.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  154.18
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  methyl (6S,9S,12S)-6-(tert-butyl)-12-(2,2-difluoroethyl)-9-(4-((7-methoxy-2-phenylquinolin-4-yl)oxy)phenyl)-2,2-dimethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 24.0h， 生成 (2S)-2-[[2-[[(2S)-3,3-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]-2-[4-(7-methoxy-2-phenylquinolin-4-yl)oxyphenyl]acetyl]amino]-4,4-difluorobutanoic acid
  参考文献：
  名称：

  Phenylglycine as a novel P2 scaffold in hepatitis C virus NS3 protease inhibitors

  摘要：

  Molecular modeling and inhibitory potencies of tetrapeptide protease inhibitors of HCV NS3 proposed phenylglycine as a new promising P2 residue. The results suggest that phenylglycine might be capable of interacting with the NS3 (protease-helicase/ NTPase) in ways not possible for the common P2 proline-based inhibitors. Thus, a series of tripeptides, both linear and macrocyclic, based on p-hydroxy-phenylglycine in the P2 position were prepared and their inhibitory effect determined. When the p-hydroxy group was replaced by methoxy, isoquinolin-, or quinolinyloxy functions, inhibitors with improved potencies were obtained. The P2 phenylglycine-based inhibitors were further optimized by C-terminal extension to acyl sulfonamides and by P1-P3 cyclization, which gave products with inhibition constants in the nanomolar range (similar to 75 nM). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.11.003
• 作为产物：
  描述：

  4-氯-7-甲氧基-2-苯基喹啉 在 盐酸 、 potassium tert-butylate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 193.75h， 生成 methyl (6S,9S,12S)-6-(tert-butyl)-12-(2,2-difluoroethyl)-9-(4-((7-methoxy-2-phenylquinolin-4-yl)oxy)phenyl)-2,2-dimethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oate
  参考文献：
  名称：

  Phenylglycine as a novel P2 scaffold in hepatitis C virus NS3 protease inhibitors

  摘要：

  Molecular modeling and inhibitory potencies of tetrapeptide protease inhibitors of HCV NS3 proposed phenylglycine as a new promising P2 residue. The results suggest that phenylglycine might be capable of interacting with the NS3 (protease-helicase/ NTPase) in ways not possible for the common P2 proline-based inhibitors. Thus, a series of tripeptides, both linear and macrocyclic, based on p-hydroxy-phenylglycine in the P2 position were prepared and their inhibitory effect determined. When the p-hydroxy group was replaced by methoxy, isoquinolin-, or quinolinyloxy functions, inhibitors with improved potencies were obtained. The P2 phenylglycine-based inhibitors were further optimized by C-terminal extension to acyl sulfonamides and by P1-P3 cyclization, which gave products with inhibition constants in the nanomolar range (similar to 75 nM). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.11.003