(2R)-2-(dimethylamino)-1-[(2S)-2-[5-(2-{2-[(2S)-1-[(2R)-2-(dimethylamino)-2-phenylacetyl]pyrrolidin-2-yl]-1,3-benzoxazol-5-yl}ethynyl)-1,3-benzoxazol-2-yl]pyrrolidin-1-yl]-2-phenylethan-1-one | 1541243-44-0

• 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)-2-(dimethylamino)-1-[(2S)-2-[5-(2-{2-[(2S)-1-[(2R)-2-(dimethylamino)-2-phenylacetyl]pyrrolidin-2-yl]-1,3-benzoxazol-5-yl}ethynyl)-1,3-benzoxazol-2-yl]pyrrolidin-1-yl]-2-phenylethan-1-one
• 英文别名: (2R)-2-(dimethylamino)-1-[(2S)-2-[5-[2-[2-[(2S)-1-[(2R)-2-(dimethylamino)-2-phenyl-acetyl]pyrrolidin-2-yl]-1,3-benzoxazol-5-yl]ethynyl]-1,3-benzoxazol-2-yl]pyrrolidin-1-yl]-2-phenyl-ethanone；(2R)-2-(dimethylamino)-1-[(2S)-2-[5-[2-[2-[(2S)-1-[(2R)-2-(dimethylamino)-2-phenylacetyl]pyrrolidin-2-yl]-1,3-benzoxazol-5-yl]ethynyl]-1,3-benzoxazol-2-yl]pyrrolidin-1-yl]-2-phenylethanone
• CAS: 1541243-44-0
• 化学式: C₄₄H₄₄N₆O₄
• 分子量: 720.871
• InChiKey: VBTYYXGXPNVIIP-JEGXQRANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  54
• 可旋转键数：
  10
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  99.2
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-氨基-4-溴苯酚 在 四(三苯基膦)钯 、 偶氮二甲酸二异丙酯 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三苯基膦 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.8h， 生成 (2R)-2-(dimethylamino)-1-[(2S)-2-[5-(2-{2-[(2S)-1-[(2R)-2-(dimethylamino)-2-phenylacetyl]pyrrolidin-2-yl]-1,3-benzoxazol-5-yl}ethynyl)-1,3-benzoxazol-2-yl]pyrrolidin-1-yl]-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