2-phenyl-1-[(2S)-2-[6-(2-{2-[(2S)-1-(2-phenylacetyl)-pyrrolidin-2-yl]-1,3-benzoxazol-6-yl}ethynyl)-1,3-benzoxazol-2-yl]pyrrolidin-1-yl]ethan-1-one | 1541243-47-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-phenyl-1-[(2S)-2-[6-(2-{2-[(2S)-1-(2-phenylacetyl)-pyrrolidin-2-yl]-1,3-benzoxazol-6-yl}ethynyl)-1,3-benzoxazol-2-yl]pyrrolidin-1-yl]ethan-1-one
• 英文别名: 2-phenyl-1-[(2S)-2-[6-[2-[2-[(2S)-1-(2-phenylacetyl)pyrrolidin-2-yl]-1,3-benzoxazol-6-yl]ethynyl]-1,3-benzoxazol-2-yl]pyrrolidin-1-yl]ethanone
• CAS: 1541243-47-3
• 化学式: C₄₀H₃₄N₄O₄
• 分子量: 634.734
• InChiKey: QGCCPBDSTYNKDE-HEVIKAOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  48
• 可旋转键数：
  8
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  92.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 四(三苯基膦)钯 、 N,N-二异丙基乙胺 、 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 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.8h， 生成 2-phenyl-1-[(2S)-2-[6-(2-{2-[(2S)-1-(2-phenylacetyl)-pyrrolidin-2-yl]-1,3-benzoxazol-6-yl}ethynyl)-1,3-benzoxazol-2-yl]pyrrolidin-1-yl]ethan-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

文献信息

• 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
  作者：Makonen Belema、Van N. Nguyen、Jeffrey L. Romine、Denis R. St. Laurent、Omar D. Lopez、Jason T. Goodrich、Peter T. Nower、Donald R. O’Boyle、Julie A. Lemm、Robert A. Fridell、Min Gao、Hua Fang、Rudolph G. Krause、Ying-Kai Wang、A. Jayne Oliver、Andrew C. Good、Jay O. Knipe、Nicholas A. Meanwell、Lawrence B. Snyder

  DOI：10.1021/jm4016203

  日期：2014.3.13

  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.