lithium 4-cyclopropylthiazole-2-carboxylate | 1180496-27-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: lithium 4-cyclopropylthiazole-2-carboxylate
• 英文别名: lithium;4-cyclopropyl-1,3-thiazole-2-carboxylate
• CAS: 1180496-27-8
• 化学式: C₇H₆NO₂S*Li
• 分子量: 175.137
• InChiKey: YKECMCRXXYJXED-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -2.61
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  81.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  lithium 4-cyclopropylthiazole-2-carboxylate 在 偶氮二甲酸二异丙酯 、 potassium tert-butylate 、 三苯基膦 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 叔丁醇 为溶剂， 反应 18.33h， 生成
  参考文献：
  名称：

  Discovery of Novel Urea-Based Hepatitis C Protease Inhibitors with High Potency against Protease-Inhibitor-Resistant Mutants

  摘要：

  The macrocyclic urea 2, a byproduct in the synthesis of benzoxaborole 1, was identified to be a novel and potent HCV protease inhibitor. We further explored this motif by synthesizing additional urea-based inhibitors and by characterizing them in replicase HCV protease-resistant mutants assay. Several compounds, exemplified by 12, were found to be more potent in HCV replicon assays than leading second generation inhibitors such as danoprevir and TMC-435350. Additionally, following oral administration, inhibitor 12 was found in rat liver in significantly higher concentrations than those reported for both danoprevir and TMC-435350, suggesting that inhibitor 12 has the combination of anti-HCV and pharmacokinetic properties that warrants further development of this series.

  DOI：

  10.1021/jm201278q
• 作为产物：
  描述：

  在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 lithium 4-cyclopropylthiazole-2-carboxylate
  参考文献：
  名称：

  Discovery of Novel Urea-Based Hepatitis C Protease Inhibitors with High Potency against Protease-Inhibitor-Resistant Mutants

  摘要：

  The macrocyclic urea 2, a byproduct in the synthesis of benzoxaborole 1, was identified to be a novel and potent HCV protease inhibitor. We further explored this motif by synthesizing additional urea-based inhibitors and by characterizing them in replicase HCV protease-resistant mutants assay. Several compounds, exemplified by 12, were found to be more potent in HCV replicon assays than leading second generation inhibitors such as danoprevir and TMC-435350. Additionally, following oral administration, inhibitor 12 was found in rat liver in significantly higher concentrations than those reported for both danoprevir and TMC-435350, suggesting that inhibitor 12 has the combination of anti-HCV and pharmacokinetic properties that warrants further development of this series.

  DOI：

  10.1021/jm201278q

文献信息

• MACROCYCLIC SERINE PROTEASE INHIBITORS
  申请人：Parsy Christophe Claude

  公开号：US20100260710A1

  公开（公告）日：2010-10-14

  Provided herein are macrocyclic serine protease inhibitor compounds, for example, of Formula Ia or Ib, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.

  本文提供了大环丝氨酸蛋白酶抑制剂化合物，例如，Ia或Ib式的化合物，包括这些化合物的药物组合物，以及其制备方法。还提供了它们用于治疗宿主HCV感染的方法。
• Macrocyclic serine protease inhibitors
  申请人：Parsy Christophe Claude

  公开号：US08377962B2

  公开（公告）日：2013-02-19

  Provided herein are macrocyclic serine protease inhibitor compounds, for example, of Formula Ia or Ib, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.

  本文提供了大环丝氨酸蛋白酶抑制剂化合物，例如Ia或Ib式的化合物，包括含有该化合物的制药组合物以及其制备方法。还提供了它们用于治疗宿主中需要治疗HCV感染的方法。
• [EN] MACROCYCLIC SERINE PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE SÉRINE PROTÉASE MACROCYCLIQUES
  申请人：IDENIX PHARAMACEUTICALS INC

  公开号：WO2009099596A2

  公开（公告）日：2009-08-13

  Provided herein are macrocyclic serine protease inhibitor compounds, for example, of Formula (I), pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.