4-[[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carbonyl]amino]benzoic acid | 1241379-64-5

• 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: 4-[[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carbonyl]amino]benzoic acid
• CAS: 1241379-64-5
• 化学式: C₁₇H₂₂N₂O₅
• 分子量: 334.372
• InChiKey: VYLJNTCTXSDNGT-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carbonyl]amino]benzoic acid 在 盐酸 、 ammonium hydroxide 、 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 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.08h， 生成 (S)-N-(4-(5-(2-((S)-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：

  BOC-L-脯氨酸 、 对氨基苯甲酸 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以44%的产率得到4-[[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carbonyl]amino]benzoic acid
  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

• [EN] HEPATITIS C VIRUS INHIBITORS<br/>[FR] INHIBITEURS DU VIRUS DE L'HÉPATITE C
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2012018325A1

  公开（公告）日：2012-02-09

  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以及使用这些化合物治疗HCV感染的方法。
• Hepatitis C Virus Inhibitors
  申请人：Romine Jeffrey Lee

  公开号：US20100215616A1

  公开（公告）日：2010-08-26

  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以及使用这些化合物治疗HCV感染的方法。
• US8394968B2
  申请人：——

  公开号：US8394968B2

  公开（公告）日：2013-03-12
• US8809548B2
  申请人：——

  公开号：US8809548B2

  公开（公告）日：2014-08-19
• 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.