ethyl 2-{N-[(methyloxy)carbonyl]-L-valyl}-8-thia-2-azaspiro[4.5]decane-3-carboxylic acid 8,8-dioxide | 1272655-81-8

• 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: ethyl 2-{N-[(methyloxy)carbonyl]-L-valyl}-8-thia-2-azaspiro[4.5]decane-3-carboxylic acid 8,8-dioxide
• 英文别名: 2-{N-[(methyloxy)carbonyl]-L-valyl}-8-thia-2-azaspiro[4.5]decane-3-carboxylic acid 8,8-dioxide；2-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]-8,8-dioxo-8λ6-thia-2-azaspiro[4.5]decane-3-carboxylic acid
• CAS: 1272655-81-8
• 化学式: C₁₆H₂₆N₂O₇S
• 分子量: 390.458
• InChiKey: JUEVHQUPIUMFAN-KIYNQFGBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  139
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 2-{N-[(methyloxy)carbonyl]-L-valyl}-8-thia-2-azaspiro[4.5]decane-3-carboxylic acid 8,8-dioxide 、 methyl {(1S)-1-[((2S)-2-{4-[4′-(aminoacetyl)-4-biphenylyl]-1H-imidazol-2-yl}-1-pyrrolidinyl)carbonyl]-2-methylpropyl}-carbamate 在 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 methyl N-[(2S)-1-[3-({2-[4-(4-{2-[(2S)-1-[(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl]pyrrolidin-2-yl]-1H-imidazol-5-yl}phenyl)phenyl]-2-oxoethyl}carbamoyl)-8,8-dioxido-8-thia-2-azaspiro[4.5]decan-2-yl]-3-methyl-1-oxobutan-2-yl]carbamate
  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
• 作为产物：
  描述：

  在 氢气 、 三乙胺 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 ethyl 2-{N-[(methyloxy)carbonyl]-L-valyl}-8-thia-2-azaspiro[4.5]decane-3-carboxylic acid 8,8-dioxide
  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。
• 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。
• CHEMICAL COMPOUNDS
  申请人：Janssen Pharmaceuticals, Inc.

  公开号：US20150374668A1

  公开（公告）日：2015-12-31

  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.

  本发明揭示了III式化合物。还揭示了该化合物的盐、包含该化合物或其盐的制药组合物，以及通过给予该化合物或其盐治疗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。