sodium 1-(2,2-difluoro-ethyl)-1H-pyrazole-3-carboxylate | 1309951-82-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: sodium 1-(2,2-difluoro-ethyl)-1H-pyrazole-3-carboxylate
• 英文别名: Sodium;1-(2,2-difluoroethyl)pyrazole-3-carboxylate
• CAS: 1309951-82-3
• 化学式: C₆H₅F₂N₂O₂*Na
• 分子量: 198.104
• InChiKey: ZFZYXIPUFGUCCL-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -3.48
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  58
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  sodium 1-(2,2-difluoro-ethyl)-1H-pyrazole-3-carboxylate 、 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.25h， 生成 (2R,6S,12Z,13aS,14aR,16aS)-6-({[1-(2,2-difluoroethyl)-1H-pyrazol-3-yl]carbonyl}amino)-2-{[7-methoxy-8-methyl-2-(propan-2-yloxy)quinolin-4-yl]oxy}-N-[(1-methylcyclopropyl)sulfonyl]-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxamide
  参考文献：
  名称：

  [EN] HEPATITIS C INHIBITOR COMPOUNDS
  [FR] COMPOSÉS INHIBITEURS DE L'HÉPATITE C

  摘要：

  本发明的化合物是含有酰磺酰胺基团的大环肽类似物，对包含临床相关耐药突变的NS3蛋白酶保持良好的活性，这些耐药突变由基因型1a的R155K、基因型1b的D168V和基因型1a的D168V耐药突变代表。本发明的化合物可用作HCV NS3蛋白酶的抑制剂，用于治疗丙型肝炎病毒感染。

  公开号：

  WO2011063501A1
• 作为产物：
  描述：

  Ethyl 1-(2,2-difluoroethyl)pyrazole-3-carboxylate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 4.0h， 生成 sodium 1-(2,2-difluoro-ethyl)-1H-pyrazole-3-carboxylate
  参考文献：
  名称：

  Discovery of Hepatitis C Virus NS3-4A Protease Inhibitors with Improved Barrier to Resistance and Favorable Liver Distribution

  摘要：

  Given the emergence of resistance observed for the current clinical-stage hepatitis C virus (HCV) NS3 protease inhibitors, there is a need for new inhibitors with a higher barrier to resistance. We recently reported our rational approach to the discovery of macrocyclic acylsulfonamides as HCV protease inhibitors addressing potency against clinically relevant resistant variants. Using X-ray crystallography of HCV protease variant/inhibitor complexes, we shed light on the complex structural mechanisms by which the D168V and R155K residue mutations confer resistance to NS3 protease inhibitors. Here, we disclose SAR investigation and ADME/PK optimization leading to the identification of inhibitors with significantly Unproved potency against the key resistant variants and with increased liver partitioning.

  DOI：

  10.1021/jm400121t

文献信息

• HEPATITIS C INHIBITOR COMPOUNDS
  申请人：Llinas-Brunet Montse

  公开号：US20120077737A1

  公开（公告）日：2012-03-29

  Compounds of the invention, which are macrocyclic peptide analogs containing an acylsulfonamide moiety, maintain good activity against NS3 proteases containing clinically relevant resistance mutations for this class as represented by genotype 1a R155K, genotype 1b D168V and genotype 1a D168V resistance mutations. The compounds of the invention are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.

  本发明的化合物是含有酰基磺酰胺基团的大环肽类似物，在对于该类别的NS3蛋白酶含有临床相关的耐药突变，如基因型1a R155K、基因型1b D168V和基因型1a D168V耐药突变时，仍然保持良好的活性。本发明的化合物可用作HCV NS3蛋白酶的抑制剂，用于治疗丙型肝炎病毒感染。
• [EN] HEPATITIS C INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS DE L'HÉPATITE C
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2011063501A1

  公开（公告）日：2011-06-03

  Compounds of the invention, which are macrocyclic peptide analogs containing an acylsulfonamide moiety, maintain good activity against NS3 proteases containing clinically relevant resistance mutations for this class as represented by genotype 1 a R155K, genotype 1 b D168V and genotype 1 a D168V resistance mutations. The compounds of the invention are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.

  本发明的化合物是含有酰磺酰胺基团的大环肽类似物，对包含临床相关耐药突变的NS3蛋白酶保持良好的活性，这些耐药突变由基因型1a的R155K、基因型1b的D168V和基因型1a的D168V耐药突变代表。本发明的化合物可用作HCV NS3蛋白酶的抑制剂，用于治疗丙型肝炎病毒感染。
• Discovery of Hepatitis C Virus NS3-4A Protease Inhibitors with Improved Barrier to Resistance and Favorable Liver Distribution
  作者：Benoît Moreau、Jeff A. O’Meara、Josée Bordeleau、Michel Garneau、Cedrickx Godbout、Vida Gorys、Mélissa Leblanc、Elisia Villemure、Peter W. White、Montse Llinàs-Brunet

  DOI：10.1021/jm400121t

  日期：2014.3.13

  Given the emergence of resistance observed for the current clinical-stage hepatitis C virus (HCV) NS3 protease inhibitors, there is a need for new inhibitors with a higher barrier to resistance. We recently reported our rational approach to the discovery of macrocyclic acylsulfonamides as HCV protease inhibitors addressing potency against clinically relevant resistant variants. Using X-ray crystallography of HCV protease variant/inhibitor complexes, we shed light on the complex structural mechanisms by which the D168V and R155K residue mutations confer resistance to NS3 protease inhibitors. Here, we disclose SAR investigation and ADME/PK optimization leading to the identification of inhibitors with significantly Unproved potency against the key resistant variants and with increased liver partitioning.