(2R,5S)-N-(2,2-dimethoxyethyl)-4-(5-(4-fluorophenyl)-isoxazole-3-carbonyl)-5-isobutyl-6-oxopiperazine-2-carboxamide | 1391630-01-5

• 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: (2R,5S)-N-(2,2-dimethoxyethyl)-4-(5-(4-fluorophenyl)-isoxazole-3-carbonyl)-5-isobutyl-6-oxopiperazine-2-carboxamide
• 英文别名: (2R,5S)-N-(2,2-dimethoxyethyl)-4-[5-(4-fluorophenyl)-1,2-oxazole-3-carbonyl]-5-(2-methylpropyl)-6-oxopiperazine-2-carboxamide
• CAS: 1391630-01-5
• 化学式: C₂₃H₂₉FN₄O₆
• 分子量: 476.505
• InChiKey: VIPWQZDRNRQEOL-MSOLQXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2R,5S)-N-(2,2-dimethoxyethyl)-4-(5-(4-fluorophenyl)-isoxazole-3-carbonyl)-5-isobutyl-6-oxopiperazine-2-carboxamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以75%的产率得到(3S,6R)-4-(5-(4-fluorophenyl)isoxazole-3-carbonyl)-3-isobutyl-6-(oxazol-2-yl)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：

  5-(4-氟苯基)异噁唑-3-羧酸 在 Oxone 、 四氧化锇 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 乙腈 、 叔丁醇 为溶剂， 反应 3.0h， 生成 (2R,5S)-N-(2,2-dimethoxyethyl)-4-(5-(4-fluorophenyl)-isoxazole-3-carbonyl)-5-isobutyl-6-oxopiperazine-2-carboxamide
  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

文献信息

• [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。
• 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。