(8S)-7-{N-[(methyloxy)carbonyl]-L-valyl}-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid | 1296797-34-6

• 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: (8S)-7-{N-[(methyloxy)carbonyl]-L-valyl}-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid
• 英文别名: (8S)-7-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid
• CAS: 1296797-34-6
• 化学式: C₁₄H₂₂N₂O₅S₂
• 分子量: 362.471
• InChiKey: FBNUQARZZIQFIR-UWVGGRQHSA-N

物化性质

• 沸点：
  614.8±55.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  147
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (8S)-7-{N-[(methyloxy)carbonyl]-L-valyl}-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid 、 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
  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：

  (S)-methyl 1-((S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-4-oxopyrrolidine-2-carboxylate 在 对甲苯磺酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 (8S)-7-{N-[(methyloxy)carbonyl]-L-valyl}-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid
  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：WO2011050146A1

  公开（公告）日：2011-04-28

  Disclosed are compounds of Formula (I). Also disclosed are pharmaceutical compositions comprising the compounds, and methods for treating HCV invention by administration of the compounds.

  揭示了化合物的化学式（I）。还揭示了包含这些化合物的药物组合物，以及通过给药这些化合物来治疗HCV的方法。
• Novel Spiroketal Pyrrolidine GSK2336805 Potently Inhibits Key Hepatitis C Virus Genotype 1b Mutants: From Lead to Clinical Compound
  作者：Wieslaw M. Kazmierski、Andrew Maynard、Maosheng Duan、Sam Baskaran、Janos Botyanszki、Renae Crosby、Scott Dickerson、Matthew Tallant、Rick Grimes、Robert Hamatake、Martin Leivers、Christopher D. Roberts、Jill Walker

  DOI：10.1021/jm4013104

  日期：2014.3.13

  [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.