methyl ((2S)-1-(7-((2-(4'-(2-((S)-1-((methoxycarbonyl)-L-valyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-[1,1'-biphenyl]-4-yl)-2-oxoethyl)carbamoyl)-2-(methylcarbamoyl)-2,6-diazaspiro[3.4]octan-6-yl)-3-methyl-1-oxobutan-2-yl)carbamate | 1571137-99-9

• 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: methyl ((2S)-1-(7-((2-(4'-(2-((S)-1-((methoxycarbonyl)-L-valyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-[1,1'-biphenyl]-4-yl)-2-oxoethyl)carbamoyl)-2-(methylcarbamoyl)-2,6-diazaspiro[3.4]octan-6-yl)-3-methyl-1-oxobutan-2-yl)carbamate
• CAS: 1571137-99-9
• 化学式: C₄₄H₅₇N₉O₉
• 分子量: 855.991
• InChiKey: ILXKCQQHXMYVCD-WLRQVOJESA-N

物化性质

• 沸点：
  1176.7±65.0 °C(predicted)
• 密度：
  1.35±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.71
• 重原子数：
  62.0
• 可旋转键数：
  13.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  224.47
• 氢给体数：
  5.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  methyl ((2S)-1-(7-((2-(4'-(2-((S)-1-((methoxycarbonyl)-L-valyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-[1,1'-biphenyl]-4-yl)-2-oxoethyl)carbamoyl)-2-(methylcarbamoyl)-2,6-diazaspiro[3.4]octan-6-yl)-3-methyl-1-oxobutan-2-yl)carbamate 在 ammonium acetate 作用下， 以 1,4-二氧六环 为溶剂， 生成 methyl [(1S)-2-methyl-1-({(2S)-2-[4-(4′-{2-[2-[(methylamino)-carbonyl]-6-((2S)-3-methyl-2-{[(methyloxy)carbonyl]amino}-butanoyl)-2,6-diazaspiro[3.4]oct-7-yl]-1H-imidazol-4-yl}-4-biphenylylbiphenylyl)-1H-imidazol-2-yl]-1-pyrrolidinyl}carbonyl)propyl]-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 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 methyl ((2S)-1-(7-((2-(4'-(2-((S)-1-((methoxycarbonyl)-L-valyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-[1,1'-biphenyl]-4-yl)-2-oxoethyl)carbamoyl)-2-(methylcarbamoyl)-2,6-diazaspiro[3.4]octan-6-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