methyl 5-(3,3-dimethylbut-1-ynyl)-3-(2,2,2-trifluoroacetamido)thiophene-2-carboxylate | 1612898-48-2

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: methyl 5-(3,3-dimethylbut-1-ynyl)-3-(2,2,2-trifluoroacetamido)thiophene-2-carboxylate
• 英文别名: Methyl 5-(3,3-dimethylbut-1-yn-1-yl)-3-(2,2,2-trifluoroacetamido)thiophene-2-carboxylate；methyl 5-(3,3-dimethylbut-1-ynyl)-3-[(2,2,2-trifluoroacetyl)amino]thiophene-2-carboxylate
• CAS: 1612898-48-2
• 化学式: C₁₄H₁₄F₃NO₃S
• 分子量: 333.331
• InChiKey: RJCQAUOVXUPIIS-UHFFFAOYSA-N

物化性质

• 沸点：
  433.8±45.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 5-(3,3-dimethylbut-1-ynyl)-3-(2,2,2-trifluoroacetamido)thiophene-2-carboxylate 在 potassium carbonate 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 2.5h， 以91%的产率得到methyl 3-amino-5-(3,3-dimethylbut-1-ynyl)thiophene-2-carboxylate
  参考文献：
  名称：

  Discovery of GS-9669, a Thumb Site II Non-Nucleoside Inhibitor of NS5B for the Treatment of Genotype 1 Chronic Hepatitis C Infection

  摘要：

  Investigation of thiophene-2-carboxylic acid HCV NS5B site II inhibitors, guided by measurement of cell culture medium binding, revealed the structure activity relationships for intrinsic cellular potency. The pharmacokinetic profile was enhanced through incorporation of heterocyclic ethers on the N-alkyl substituent. Hydroxyl groups were incorporated to modulate protein binding. Intrinsic potency was further improved through enantiospecific introduction of an olefin in the N-acyl motif, resulting in the discovery of the phase 2 clinical candidate GS-9669. The unexpected activity of this compound against the clinically relevant NS5B M423T mutant, relative to the wild type, was shown to arise from both the N-alkyl substituent and the N-acyl group.

  DOI：

  10.1021/jm401420j
• 作为产物：
  描述：

  3-(N-三氟乙酰氨基)噻吩-2-羧酸甲酯 在 bis-triphenylphosphine-palladium(II) chloride 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.17h， 生成 methyl 5-(3,3-dimethylbut-1-ynyl)-3-(2,2,2-trifluoroacetamido)thiophene-2-carboxylate
  参考文献：
  名称：

  Discovery of GS-9669, a Thumb Site II Non-Nucleoside Inhibitor of NS5B for the Treatment of Genotype 1 Chronic Hepatitis C Infection

  摘要：

  Investigation of thiophene-2-carboxylic acid HCV NS5B site II inhibitors, guided by measurement of cell culture medium binding, revealed the structure activity relationships for intrinsic cellular potency. The pharmacokinetic profile was enhanced through incorporation of heterocyclic ethers on the N-alkyl substituent. Hydroxyl groups were incorporated to modulate protein binding. Intrinsic potency was further improved through enantiospecific introduction of an olefin in the N-acyl motif, resulting in the discovery of the phase 2 clinical candidate GS-9669. The unexpected activity of this compound against the clinically relevant NS5B M423T mutant, relative to the wild type, was shown to arise from both the N-alkyl substituent and the N-acyl group.

  DOI：

  10.1021/jm401420j