( 3S,6S)-3,6-diiso-butyl-4-((1R,2R)-2-phenylcyclopropanecarbonyl)piperazin-2-one | 1391625-53-8

• 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)-3,6-diiso-butyl-4-((1R,2R)-2-phenylcyclopropanecarbonyl)piperazin-2-one
• 英文别名: (3S,6S)-3,6-diisobutyl-4-((1R,2R)-2-phenylcyclopropanecarbonyl)piperazin-2-one；(3S,6S)-3,6-diisobutyl-4-[(1R,2R)-2-phenylcyclopropanecarbonyl]piperazin-2-one；(3S,6S)-3,6-bis(2-methylpropyl)-4-[(1R,2R)-2-phenylcyclopropanecarbonyl]piperazin-2-one
• CAS: 1391625-53-8
• 化学式: C₂₂H₃₂N₂O₂
• 分子量: 356.508
• InChiKey: QWAYUNUQNGRNBW-HAGHYFMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  ( 3S,6S)-3,6-diiso-butyl-4-((1R,2R)-2-phenylcyclopropanecarbonyl)piperazin-2-one 、 碘甲烷 在 BMAP 作用下， 以 二氯甲烷 为溶剂， 反应 36.0h， 以12%的产率得到(3S,6S)-3,6-d iisobutyl-1-methyl-4-((1R,2R)-2-phenylcyclopropanecarbonyl)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
• 作为产物：
  描述：

  (1R,2R)-trans-2-phenyl-1-cyclopropanecarboxylic acid 、 (3S,6S)-3,6-diisobutylpiperazin-2-one 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 3.08h， 以90%的产率得到( 3S,6S)-3,6-diiso-butyl-4-((1R,2R)-2-phenylcyclopropanecarbonyl)piperazin-2-one
  参考文献：
  名称：

  [EN] PYRAZINE AND IMIDAZOLIDINE DERIVATIVES AND THEIR USES TO TREAT HEPATITIS C
  [FR] DÉRIVÉS DE PYRAZINE ET D'IMIDAZOLIDINE ET LEURS UTILISATIONS EN VUE DU TRAITEMENT DE L'HÉPATITE C

  摘要：

  本文披露了一些用于治疗病毒感染，如HCV的化合物。

  公开号：

  WO2012103113A1

文献信息

• COMPOUNDS
  申请人：SOFIA MICHAEL JOSEPH

  公开号：US20120202794A1

  公开（公告）日：2012-08-09

  Disclosed herein are compounds useful for treating a viral infection, such as HCV.

  本文公开了用于治疗病毒感染，如HCV的化合物。
• Discovery of a Novel Class of Potent HCV NS4B Inhibitors: SAR Studies on Piperazinone Derivatives
  作者：Ramesh Kakarla、Jian Liu、Devan Naduthambi、Wonsuk Chang、Ralph T. Mosley、Donghui Bao、Holly M. Micolochick Steuer、Meg Keilman、Shalini Bansal、Angela M. Lam、William Seibel、Sandra Neilson、Phillip A. Furman、Michael J. Sofia

  DOI：10.1021/jm4012643

  日期：2014.3.13

  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.
• [EN] PYRAZINE AND IMIDAZOLIDINE DERIVATIVES AND THEIR USES TO TREAT HEPATITIS C<br/>[FR] DÉRIVÉS DE PYRAZINE ET D'IMIDAZOLIDINE ET LEURS UTILISATIONS EN VUE DU TRAITEMENT DE L'HÉPATITE C
  申请人：GILEAD PHARMASSET LLC

  公开号：WO2012103113A1

  公开（公告）日：2012-08-02

  Disclosed herein are compounds useful for treating a viral infection, such HCV.

  本文披露了一些用于治疗病毒感染，如HCV的化合物。