tert-butyl (2S)-2-[6-[2-[2-[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-2-yl]-3H-benzimidazol-5-yl]-1,3-oxazol-5-yl]-1H-benzimidazol-2-yl]pyrrolidine-1-carboxylate | 1208010-18-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: tert-butyl (2S)-2-[6-[2-[2-[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-2-yl]-3H-benzimidazol-5-yl]-1,3-oxazol-5-yl]-1H-benzimidazol-2-yl]pyrrolidine-1-carboxylate
• CAS: 1208010-18-7
• 化学式: C₃₅H₄₁N₇O₅
• 分子量: 639.754
• InChiKey: RBBRDEJORNVURF-SVBPBHIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  47
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  143
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S)-2-[6-[2-[2-[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-2-yl]-3H-benzimidazol-5-yl]-1,3-oxazol-5-yl]-1H-benzimidazol-2-yl]pyrrolidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 17.0h， 生成 5-(2-((S)-pyrrolidin-2-yl)-1H-benzo[d]imidazol-5-yl)-2-(2-((S)-pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl)oxazole
  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：

  3,4-二氨基苯甲酸甲酯 在 甲醇 、 六氯乙烷 、 N-甲基吗啉氧化物 、 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 、 sodium hydroxide 、 氯甲酸异丁酯 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 64.42h， 生成 tert-butyl (2S)-2-[6-[2-[2-[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-2-yl]-3H-benzimidazol-5-yl]-1,3-oxazol-5-yl]-1H-benzimidazol-2-yl]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

文献信息

• HEPATITIS C VIRUS INHIBITORS
  申请人：Belema Makonen

  公开号：US20100068176A1

  公开（公告）日：2010-03-18

  The present disclosure relates to compounds, compositions and methods for the treatment of Hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.

  本公开涉及化合物、组合物和治疗丙型肝炎病毒（HCV）感染的方法。还公开了含有这些化合物的药物组合物，并公开了使用这些化合物治疗HCV感染的方法。
• US7906655B2
  申请人：——

  公开号：US7906655B2

  公开（公告）日：2011-03-15
• 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.