ethyl (1R,2S)-1-((S)-2-((tert-butoxycarbonyl)amino)-2-(4-((3-(pyridin-4-yl)isoquinolin-1-yl)oxy)phenyl)acetamido)-2-vinylcyclopropane-1-carboxylate | 928162-50-9

• 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: ethyl (1R,2S)-1-((S)-2-((tert-butoxycarbonyl)amino)-2-(4-((3-(pyridin-4-yl)isoquinolin-1-yl)oxy)phenyl)acetamido)-2-vinylcyclopropane-1-carboxylate
• CAS: 928162-50-9
• 化学式: C₃₅H₃₆N₄O₆
• 分子量: 608.694
• InChiKey: IKUUAHQRWRDBIW-HXVSLEDBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.28
• 重原子数：
  45.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  128.74
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  ethyl (1R,2S)-1-((S)-2-((tert-butoxycarbonyl)amino)-2-(4-((3-(pyridin-4-yl)isoquinolin-1-yl)oxy)phenyl)acetamido)-2-vinylcyclopropane-1-carboxylate 在 Grubbs catalyst first generation 盐酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 、 甲苯 为溶剂， 生成
  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：

  N-BOC-S-对羟基苯甘氨酸 在 tris(dibenzylideneacetone)dipalladium (0) potassium fluoride 、 potassium tert-butylate 、 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 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 四氢呋喃 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 336.25h， 生成 ethyl (1R,2S)-1-((S)-2-((tert-butoxycarbonyl)amino)-2-(4-((3-(pyridin-4-yl)isoquinolin-1-yl)oxy)phenyl)acetamido)-2-vinylcyclopropane-1-carboxylate
  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