(S)-2-(4′-(2-bromoacetyl)-[1,1′-biphenyl]-4-yl)-2-oxoethyl-1-((S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-pyrrolidine-2-carboxylate | 1272655-89-6

• 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: (S)-2-(4′-(2-bromoacetyl)-[1,1′-biphenyl]-4-yl)-2-oxoethyl-1-((S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-pyrrolidine-2-carboxylate
• 英文别名: 2-[4'-(bromoacetyl)-4-biphenylyl]-2-oxoethyl N-[(methyloxy)carbonyl]-L-valyl-L-prolinate；[2-[4-[4-(2-bromoacetyl)phenyl]phenyl]-2-oxoethyl] (2S)-1-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]pyrrolidine-2-carboxylate
• CAS: 1272655-89-6
• 化学式: C₂₈H₃₁BrN₂O₇
• 分子量: 587.467
• InChiKey: DELCNAKCLRAMPX-DHLKQENFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  38
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (7S)-2,2-difluoro-6-{N-[(methyloxy)carbonyl]-L-valyl}-6-azaspiro[3.4]octane-7-carboxylic acid 、 (S)-2-(4′-(2-bromoacetyl)-[1,1′-biphenyl]-4-yl)-2-oxoethyl-1-((S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-pyrrolidine-2-carboxylate 以to afford the title compound as a white solid (104 mg, 75% yield)的产率得到2-(4'-(((((2S)-1-((2S)-3-methyl-2-(((methyloxy)carbonyl)amino)butanoyl)-2-pyrrolidinyl)carbonyl)oxy)acetyl)-4-biphenylyl)-2-oxoethyl (7S)-2.2-difluoro-6-((2S)-3-methyl-2-(((methyloxy)carbonyl)amino)butanoyl)-6-azaspiro[3.4]octane-7-carboxylate
  参考文献：
  名称：

  Chemical compounds

  摘要：

  本发明涉及III式化合物。本发明还涉及化合物的盐、包含所述化合物或盐的药物组合物以及通过给予所述化合物或盐治疗HCV感染的方法。

  公开号：

  US08344155B2
• 作为产物：
  描述：

  4,4'-二(2-溴乙酰基)联苯 、 N-(甲氧羰基)-L-缬氨酰-L-脯氨酸 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 1.75h， 以37.3%的产率得到(S)-2-(4′-(2-bromoacetyl)-[1,1′-biphenyl]-4-yl)-2-oxoethyl-1-((S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-pyrrolidine-2-carboxylate
  参考文献：
  名称：

  Novel Spiroketal Pyrrolidine GSK2336805 Potently Inhibits Key Hepatitis C Virus Genotype 1b Mutants: From Lead to Clinical Compound

  摘要：

  [GRAPHICS]Rapid clinical progress of hepatitis C virus (HCV) replication inhibitors, including these selecting for resistance in the NS5A region (NS5A inhibitors), promises to revolutionize HCV treatment. Herein, we describe our explorations of diverse spiropyrrolidine motifs in novel NS5A inhibitors and a proposed interaction model. We discovered that the 1,4-dioxa-7-azaspiro[4.4]nonane motif in inhibitor 41H (GSIC2236805) supported high potency against genotypes la and lb as well as in genotype 1b L31V and Y93H mutants. Consistent with this, 41H potently suppressed HCV RNA in the 20-day RNA reduction assay. Pharmacokinetic and safety data supported further progression of 41H to the clinic.

  DOI：

  10.1021/jm4013104

文献信息

• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011028596A1

  公开（公告）日：2011-03-10

  Disclosed are compounds of Formula III. Also disclosed are salts of the compounds, pharmaceutical composition comprising the compounds or salts, and methods for treating HCV infection by administration of the compounds or salts.

  揭示了III式化合物。还揭示了这些化合物的盐，包括这些化合物或盐的药物组合物，以及通过给予这些化合物或盐来治疗HCV感染的方法。
• Chemical Compounds
  申请人：Chen Pingyun

  公开号：US20110152237A1

  公开（公告）日：2011-06-23

  Disclosed are compounds of Formula III. Also disclosed are salts of the compounds, pharmaceutical composition comprising the compounds or salts, and methods for treating HCV infection by administration of the compounds or salts.

  本发明涉及III式化合物。本发明还涉及化合物的盐、包含化合物或盐的制药组合物以及通过给予化合物或盐治疗HCV感染的方法。
• NOVEL INHIBITORS OF HEPATITIS C VIRUS REPLICATION
  申请人：Buckman Brad

  公开号：US20110312996A1

  公开（公告）日：2011-12-22

  The embodiments provide compounds of the general Formulae VI, VII, VIII, IX, X, XI, XII, XIII, XIV, and XV as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.

  本实施例提供了通式VI、VII、VIII、IX、X、XI、XII、XIII、XIV和XV的化合物，以及包括药物组合物在内的组合物。本实施例还提供了治疗方法，包括治疗丙型肝炎病毒感染和肝纤维化的方法，通常涉及向需要的个体施用所述化合物或组合物的有效量。
• Chemical compounds
  申请人：GlaxoSmith Kline LLC

  公开号：US08344155B2

  公开（公告）日：2013-01-01

  Disclosed are compounds of Formula III. Also disclosed are salts of the compounds, pharmaceutical composition comprising the compounds or salts, and methods for treating HCV infection by administration of the compounds or salts.

  本发明涉及III式化合物。本发明还涉及化合物的盐、包含所述化合物或盐的药物组合物以及通过给予所述化合物或盐治疗HCV感染的方法。
• NS5A INHIBITORS
  申请人：Janssen Pharmaceuticals, Inc.

  公开号：EP3006441A1

  公开（公告）日：2016-04-13

  Disclosed are compounds of Formula III. Also disclosed are salts of the compounds, pharmaceutical composition comprising the compounds or salts, and methods for treating HCV infection by administration of the compounds or salts.

  公开了式 III 的化合物。还公开了这些化合物的盐、包含这些化合物或盐的药物组合物，以及通过施用这些化合物或盐治疗 HCV 感染的方法。