dimethyl (4,4′-biphenyldiylbis{1H-imidazole-4,2-diyl(3S)-8-oxa-2-azaspiro[4.5]decane-3,2-diyl[(2S)-3-methyl-1-oxo-1,2-butanediyl]})biscarbamate | 1272656-09-3

• 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: dimethyl (4,4′-biphenyldiylbis{1H-imidazole-4,2-diyl(3S)-8-oxa-2-azaspiro[4.5]decane-3,2-diyl[(2S)-3-methyl-1-oxo-1,2-butanediyl]})biscarbamate
• 英文别名: methyl N-[(1S)-1-[(2S)-2-[5-[4-[4-[2-[(2S)-3-[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]-8-oxa-3-azaspiro[4.5]decan-2-yl]-1H-imidazol-5-yl]phenyl]phenyl]-1H-imidazol-2-yl]-8-oxa-3-azaspiro[4.5]decane-3-carbonyl]-2-methyl-propyl]carbamate；methyl N-[(2S)-1-[(3S)-3-[5-[4-[4-[2-[(3S)-2-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]-8-oxa-2-azaspiro[4.5]decan-3-yl]-1H-imidazol-5-yl]phenyl]phenyl]-1H-imidazol-2-yl]-8-oxa-2-azaspiro[4.5]decan-2-yl]-3-methyl-1-oxobutan-2-yl]carbamate
• CAS: 1272656-09-3
• 化学式: C₄₈H₆₂N₈O₈
• 分子量: 879.069
• InChiKey: CYDCGTIECOWZAN-YKKXUYLKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  64
• 可旋转键数：
  13
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  193
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  [1,1'-biphenyl]-4,4'-diylbis(2-oxoethane-2,1-diyl) (3S,3'S)-bis(2-((methoxycarbonyl)-L-valyl)-8-oxa-2-azaspiro[4.5]decane-3-carboxylate) 在 ammonium acetate 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.33h， 生成 dimethyl (4,4′-biphenyldiylbis{1H-imidazole-4,2-diyl(3S)-8-oxa-2-azaspiro[4.5]decane-3,2-diyl[(2S)-3-methyl-1-oxo-1,2-butanediyl]})biscarbamate
  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

• Chemical compounds
  申请人：Janssen Pharmaceuticals, Inc.

  公开号：US20140371455A1

  公开（公告）日：2014-12-18

  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。本发明还涉及该化合物的盐、包含该化合物或盐的药物组合物以及通过给予该化合物或盐来治疗HCV感染的方法。
• Chemical Compounds
  申请人：GLAXOSMITHKLINE LLC

  公开号：US20130072690A1

  公开（公告）日：2013-03-21

  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.

  本发明公开了III式化合物。本发明还公开了该化合物的盐、包含该化合物或盐的药物组合物以及通过给予该化合物或盐治疗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。
• US8492554B2
  申请人：——

  公开号：US8492554B2

  公开（公告）日：2013-07-23
• US9150587B2
  申请人：——

  公开号：US9150587B2

  公开（公告）日：2015-10-06