(2R)-1-[(2S)-2-{5-[2-(3-aminophenyl)-1,3-oxazol-5-yl]-1H-1,3-benzodiazol-2-yl}pyrrolidin-1-yl]-2-(dimethylamino)-2-phenylethan-1-one | 1541243-57-5

• 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: (2R)-1-[(2S)-2-{5-[2-(3-aminophenyl)-1,3-oxazol-5-yl]-1H-1,3-benzodiazol-2-yl}pyrrolidin-1-yl]-2-(dimethylamino)-2-phenylethan-1-one
• CAS: 1541243-57-5
• 化学式: C₃₀H₃₀N₆O₂
• 分子量: 506.607
• InChiKey: MOXJFEWXORHIJE-AHKZPQOWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.43
• 重原子数：
  38.0
• 可旋转键数：
  6.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  104.28
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2R)-1-[(2S)-2-{5-[2-(3-aminophenyl)-1,3-oxazol-5-yl]-1H-1,3-benzodiazol-2-yl}pyrrolidin-1-yl]-2-(dimethylamino)-2-phenylethan-1-one 、 (2S)-1-[(2R)-2-(dimethylamino)-2-phenylacetyl]pyrrolidine-2-carboxylic acid 、 三氟乙酸 在 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 N,N-二甲基甲酰胺 、 甲醇 、 水 为溶剂， 反应 1.5h， 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：

  (S)-tert-butyl 2-(6-(2-azidoacetyl)-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate 在 盐酸 、 tin(II) chloride dihdyrate 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 、 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 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 58.58h， 生成 (2R)-1-[(2S)-2-{5-[2-(3-aminophenyl)-1,3-oxazol-5-yl]-1H-1,3-benzodiazol-2-yl}pyrrolidin-1-yl]-2-(dimethylamino)-2-phenylethan-1-one
  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