tert-butyl (S)-2-((3-(5-(3-nitrophenyl)oxazol-2-yl)phenyl)carbamoyl)pyrrolidine-1-carboxylate | 1541243-61-1

• 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 (S)-2-((3-(5-(3-nitrophenyl)oxazol-2-yl)phenyl)carbamoyl)pyrrolidine-1-carboxylate
• CAS: 1541243-61-1
• 化学式: C₂₅H₂₆N₄O₆
• 分子量: 478.505
• InChiKey: PQNKVFQZELPWAK-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.25
• 重原子数：
  35.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  127.81
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-2-((3-(5-(3-nitrophenyl)oxazol-2-yl)phenyl)carbamoyl)pyrrolidine-1-carboxylate 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 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 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、137.9 kPa 条件下， 反应 20.5h， 生成 (2S)-1-[(2R)-2-(dimethylamino)-2-phenylacetyl]-N-[3-(2-{3-[(2S)-1-[(2R)-2-(dimethylamino)-2-phenylacetyl]pyrrolidine-2-amido]phenyl}-1,3-oxazol-5-yl)phenyl]pyrrolidine-2-carboxamide
  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：

  (S)-tert-butyl 2-(3-(2-(3-nitrophenyl)-2-oxoethylcarbamoyl)phenylcarbamoyl)pyrrolidine-1-carboxylate 在 三乙胺 、 三苯基膦 、 六氯乙烷 作用下， 以 二氯甲烷 为溶剂， 反应 16.08h， 生成 tert-butyl (S)-2-((3-(5-(3-nitrophenyl)oxazol-2-yl)phenyl)carbamoyl)pyrrolidine-1-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