(3S,6S)-4-(5-(4-fluorophenyl)isoxazole-3-carbonyl)-3-isobutyl-6-(3,3,3-trifluoro-2-(trifluoromethyl)propyl)piperazin-2-one | 1552272-86-2

• 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: (3S,6S)-4-(5-(4-fluorophenyl)isoxazole-3-carbonyl)-3-isobutyl-6-(3,3,3-trifluoro-2-(trifluoromethyl)propyl)piperazin-2-one
• 英文别名: (3S,6S)-4-[5-(4-fluorophenyl)isoxazole-3-carbonyl]-3-isobutyl-6-[3,3,3-trifluoro-2-(trifluoromethyl)propyl]piperazin-2-one；(3S,6S)-4-[5-(4-fluorophenyl)-1,2-oxazole-3-carbonyl]-3-(2-methylpropyl)-6-[3,3,3-trifluoro-2-(trifluoromethyl)propyl]piperazin-2-one
• CAS: 1552272-86-2
• 化学式: C₂₂H₂₂F₇N₃O₃
• 分子量: 509.424
• InChiKey: YBFBFZPLOPCUBH-HOCLYGCPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  75.4
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 二乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (3S,6S)-4-(5-(4-fluorophenyl)isoxazole-3-carbonyl)-3-isobutyl-6-(3,3,3-trifluoro-2-(trifluoromethyl)propyl)piperazin-2-one
  参考文献：
  名称：

  Discovery of a Novel Class of Potent HCV NS4B Inhibitors: SAR Studies on Piperazinone Derivatives

  摘要：

  HTS screening identified compound 2a (piper-azinone derivative) as a low micromolar HCV genotype 1 (GT-1) inhibitor. Resistance mapping studies suggested that this piperazinone chemotype targets the HCV nonstructural protein NS4B. Extensive SAR studies were performed around 2a and the amide function and the C-3/C-6 cis stereochemistry of the piperazinone core were essential for HCV activity. A 10-fold increase in GT-1 potency was observed when the chiral phenylcyclopropyl amide side chain of 2a was replaced with p-fluorophenylisoxazole-carbonyl moiety (67). Replacing the C-6 nonpolar hydrophobic moiety of 67 with a phenyl moiety (95) did not diminish the GT-1 potency. A heterocyclic thiophene moiety (103) and an isoxazole moiety (108) were incorporated as isosteric replacements for the C-6 phenyl moiety (95), resulting in significant improvement in GT-1b and la potency. However, the piperazonone class of compounds lacks GT-2 activity and, consequently, were not pursued further into development.

  DOI：

  10.1021/jm4012643