((2S,5S)-2,5-diisobutylpiperazin-1-yl)((1R,2R)-2-phenylcyclopropyl)methanone | 1552272-66-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: ((2S,5S)-2,5-diisobutylpiperazin-1-yl)((1R,2R)-2-phenylcyclopropyl)methanone
• 英文别名: [(2S,5S)-2,5-diisobutylpiperazin-1-yl]-[(1R,2R)-2-phenylcyclopropyl]methanone；[(2S,5S)-2,5-bis(2-methylpropyl)piperazin-1-yl]-[(1R,2R)-2-phenylcyclopropyl]methanone
• CAS: 1552272-66-8
• 化学式: C₂₂H₃₄N₂O
• 分子量: 342.525
• InChiKey: YHOGAADWEVGJIK-XSDIEEQYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (3S,6S)-3,6-diisobutylpiperazin-2-one 在 lithium aluminium tetrahydride 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 ((2S,5S)-2,5-diisobutylpiperazin-1-yl)((1R,2R)-2-phenylcyclopropyl)methanone
  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