(S)-(9H-fluoren-9-yl)methyl (1-oxobut-3-en-2-yl)carbamate | 1391629-95-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (S)-(9H-fluoren-9-yl)methyl (1-oxobut-3-en-2-yl)carbamate
• 英文别名: 9H-fluoren-9-ylmethyl N-[(2S)-1-oxobut-3-en-2-yl]carbamate
• CAS: 1391629-95-0
• 化学式: C₁₉H₁₇NO₃
• 分子量: 307.349
• InChiKey: IYQHCSOGGHVHAA-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-(9H-fluoren-9-yl)methyl (1-oxobut-3-en-2-yl)carbamate 、 L-亮氨酸甲酯盐酸盐 在 三乙酰氧基硼氢化钠 作用下， 以 四氢呋喃 为溶剂， 以1.1 g的产率得到(S)-methyl 2-(((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)but-3-en-1-yl)amino)-4-methylpentanoate
  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：

  (S)-(9H-fluoren-9-yl)methyl (1-hydroxybut-3-en-2-yl)carbamate 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (S)-(9H-fluoren-9-yl)methyl (1-oxobut-3-en-2-yl)carbamate
  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

• 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.