methyl 5-bromo-7-(trifluoromethyl)benzofuran-2-carboxylate | 1431285-66-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: methyl 5-bromo-7-(trifluoromethyl)benzofuran-2-carboxylate
• 英文别名: Methyl 5-bromo-7-(trifluoromethyl)-1-benzofuran-2-carboxylate
• CAS: 1431285-66-3
• 化学式: C₁₁H₆BrF₃O₃
• 分子量: 323.066
• InChiKey: OTUDOALSQPJERU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  39.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 5-bromo-7-(trifluoromethyl)benzofuran-2-carboxylate 在 potassium phosphate 、 (1,5-cyclooctadiene)(methoxy)iridium(I) dimer 、 水 、 palladium diacetate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 4,4'-二叔丁基-2,2'-二吡啶 、 copper dichloride 、 lithium hydroxide 、 三环己基膦 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 11.0h， 生成 4-{[3-chloro-5-cyclopropyl-7-(trifluoromethyl)-3a,7a-dihydro-1-benzofuran-2-yl]carbonyl}-1-(trans-4-hydroxycyclohexyl)-2-piperazinone
  参考文献：
  名称：

  Hepatitis C Replication Inhibitors That Target the Viral NS4B Protein

  摘要：

  We describe the preclinical development and in vivo efficacy of a novel chemical series that inhibits hepatitis C virus replication via direct interaction with the viral nonstructural protein 4B (NS4B). Significant potency improvements were realized through isosteric modifications to our initial lead la. The temptation to improve antiviral activity while compromising physicochemical properties was tempered by the judicial use of ligand efficiency indices during lead optimization. In this manner, compound la was transformed into (+)-28a which possessed an improved antiviral profile with no increase in molecular weight and only a modest elevation in lipophilicity. Additionally, we employed a chimeric "humanized" mouse model of HCV infection to demonstrate for the first time that a small molecule with high in vitro affinity for NS4B can inhibit viral replication in vivo. This successful proof-of-concept study suggests that drugs targeting NS4B may represent a viable treatment option for curing HCV infection.

  DOI：

  10.1021/jm400125h
• 作为产物：
  描述：

  邻三氟甲基苯酚 在 溴 、 potassium carbonate 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 methyl 5-bromo-7-(trifluoromethyl)benzofuran-2-carboxylate
  参考文献：
  名称：

  Hepatitis C Replication Inhibitors That Target the Viral NS4B Protein

  摘要：

  We describe the preclinical development and in vivo efficacy of a novel chemical series that inhibits hepatitis C virus replication via direct interaction with the viral nonstructural protein 4B (NS4B). Significant potency improvements were realized through isosteric modifications to our initial lead la. The temptation to improve antiviral activity while compromising physicochemical properties was tempered by the judicial use of ligand efficiency indices during lead optimization. In this manner, compound la was transformed into (+)-28a which possessed an improved antiviral profile with no increase in molecular weight and only a modest elevation in lipophilicity. Additionally, we employed a chimeric "humanized" mouse model of HCV infection to demonstrate for the first time that a small molecule with high in vitro affinity for NS4B can inhibit viral replication in vivo. This successful proof-of-concept study suggests that drugs targeting NS4B may represent a viable treatment option for curing HCV infection.

  DOI：

  10.1021/jm400125h