tert-butyl N-[(1S)-1-[[(1R)-2-[[(1S)-1-[(1-allylcyclopropyl)sulfonylcarbamoyl]butyl]amino]-1-[4-[(7-methoxy-2-phenyl-4-quinolyl)oxy]-3-vinyl-phenyl]-2-oxo-ethyl]carbamoyl]-2,2-dimethyl-propyl]carbamate | 1241589-93-4

• 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: tert-butyl N-[(1S)-1-[[(1R)-2-[[(1S)-1-[(1-allylcyclopropyl)sulfonylcarbamoyl]butyl]amino]-1-[4-[(7-methoxy-2-phenyl-4-quinolyl)oxy]-3-vinyl-phenyl]-2-oxo-ethyl]carbamoyl]-2,2-dimethyl-propyl]carbamate
• 英文别名: tert-butyl N-[(2S)-1-[[(1R)-1-[3-ethenyl-4-(7-methoxy-2-phenylquinolin-4-yl)oxyphenyl]-2-oxo-2-[[(2S)-1-oxo-1-[(1-prop-2-enylcyclopropyl)sulfonylamino]pentan-2-yl]amino]ethyl]amino]-3,3-dimethyl-1-oxobutan-2-yl]carbamate
• CAS: 1241589-93-4
• 化学式: C₄₈H₅₉N₅O₉S
• 分子量: 882.091
• InChiKey: GJXXYKVCGUMFBF-XZEUHSQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9
• 重原子数：
  63
• 可旋转键数：
  21
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  200
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  N-Boc-L-叔亮氨酸 、 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以15.3%的产率得到tert-butyl N-[(1S)-1-[[(1S)-2-[[(1S)-1-[(1-allylcyclopropyl)sulfonylcarbamoyl]butyl]amino]-1-[4-[(7-methoxy-2-phenyl-4-quinolyl)oxy]-3-vinyl-phenyl]-2-oxo-ethyl]carbamoyl]-2,2-dimethyl-propyl]carbamate
  参考文献：
  名称：

  Improved P2 phenylglycine-based hepatitis C virus NS3 protease inhibitors with alkenylic prime-side substituents

  摘要：

  Phenylglycine has proved to be a useful P2 residue in HCV NS3 protease inhibitors. A novel pi-pi-interaction between the phenylglycine and the catalytic H57 residue of the protease is postulated. We hypothesized that the introduction of a vinyl on the phenylglycine might strengthen this pi-pi-interaction. Thus, herein is presented the synthesis and inhibitory potency of a series of acyclic vinylated phenylglycine-based HCV NS3 protease inhibitors. Surprisingly, inhibitors based on both D-and L-phenylglycine were found to be effective inhibitors, with a slight preference for the D-epimers. Furthermore, prime-side alkenylic extension of the C-terminal acylsulfonamide group gave significantly improved inhibitors with potencies in the nanomolar range (similar to 35 nM), potencies which were retained on mutant variants of the protease. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.05.027

文献信息

• Improved P2 phenylglycine-based hepatitis C virus NS3 protease inhibitors with alkenylic prime-side substituents
  作者：Anna Lampa、Angelica E. Ehrenberg、Sofia S. Gustafsson、Aparna Vema、Eva Åkerblom、Gunnar Lindeberg、Anders Karlén、U. Helena Danielson、Anja Sandström

  DOI：10.1016/j.bmc.2010.05.027

  日期：2010.7

  Phenylglycine has proved to be a useful P2 residue in HCV NS3 protease inhibitors. A novel pi-pi-interaction between the phenylglycine and the catalytic H57 residue of the protease is postulated. We hypothesized that the introduction of a vinyl on the phenylglycine might strengthen this pi-pi-interaction. Thus, herein is presented the synthesis and inhibitory potency of a series of acyclic vinylated phenylglycine-based HCV NS3 protease inhibitors. Surprisingly, inhibitors based on both D-and L-phenylglycine were found to be effective inhibitors, with a slight preference for the D-epimers. Furthermore, prime-side alkenylic extension of the C-terminal acylsulfonamide group gave significantly improved inhibitors with potencies in the nanomolar range (similar to 35 nM), potencies which were retained on mutant variants of the protease. (C) 2010 Elsevier Ltd. All rights reserved.