tert-butyl (2S)-1-[(2R)-2-(dimethylamino)-2-phenylacetyl]pyrrolidine-2-carboxylate | 1541243-58-6

• 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 (2S)-1-[(2R)-2-(dimethylamino)-2-phenylacetyl]pyrrolidine-2-carboxylate
• CAS: 1541243-58-6
• 化学式: C₁₉H₂₈N₂O₃
• 分子量: 332.443
• InChiKey: FCOUUIDBNDDZEF-JKSUJKDBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.62
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  49.85
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S)-1-[(2R)-2-(dimethylamino)-2-phenylacetyl]pyrrolidine-2-carboxylate 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 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (S)-1-((R)-2-(dimethylamino)-2-phenylacetyl)-N-(3-(5-(2-((S)-1-((R)-2-(dimethylamino)-2-phenylacetyl)pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl)oxazol-2-yl)phenyl)pyrrolidine-2-carboxamide trifluoroacetate
  参考文献：
  名称：

  Hepatitis C Virus NS5A Replication Complex Inhibitors. Part 6: Discovery of a Novel and Highly Potent Biarylimidazole Chemotype with Inhibitory Activity Toward Genotypes 1a and 1b Replicons

  摘要：

  A medicinal chemistry campaign that was conducted to address a potential genotoric liability associated with an aniline-derived scaffold in a series of HCV NS5A inhibitors with dual GT-1a/-1b inhibitory activity is described. Anilides 3b and 3c were used as vehicles to explore structural modifications that retained antiviral potency while removing the potential for metabolism-based unmasking of the embedded aniline. This effort resulted in the discovery of a highly potent biarylimidazole chemotype that established a potency benchmark in replicon assays, particularly toward HCV GT-1a, a strain with significant clinical importance. Securing potent GT-1a activity in a chemotype class lacking overt structural liabilities was a critical Milestone in the effort to realize the full clinical potential of targeting the HCV NS5A protein.

  DOI：

  10.1021/jm4016203
• 作为产物：
  描述：

  (R)-2-(dimethylamino)-2-phenylacetic acid hydrochloride 、 BOC-L-脯氨酸 在 N-甲基吗啉氧化物 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 tert-butyl (2S)-1-[(2R)-2-(dimethylamino)-2-phenylacetyl]pyrrolidine-2-carboxylate
  参考文献：
  名称：

  Hepatitis C Virus NS5A Replication Complex Inhibitors. Part 6: Discovery of a Novel and Highly Potent Biarylimidazole Chemotype with Inhibitory Activity Toward Genotypes 1a and 1b Replicons

  摘要：

  A medicinal chemistry campaign that was conducted to address a potential genotoric liability associated with an aniline-derived scaffold in a series of HCV NS5A inhibitors with dual GT-1a/-1b inhibitory activity is described. Anilides 3b and 3c were used as vehicles to explore structural modifications that retained antiviral potency while removing the potential for metabolism-based unmasking of the embedded aniline. This effort resulted in the discovery of a highly potent biarylimidazole chemotype that established a potency benchmark in replicon assays, particularly toward HCV GT-1a, a strain with significant clinical importance. Securing potent GT-1a activity in a chemotype class lacking overt structural liabilities was a critical Milestone in the effort to realize the full clinical potential of targeting the HCV NS5A protein.

  DOI：

  10.1021/jm4016203