2,6-dichloro-N-((3S,4S)-3-fluoro-1-isopropylpiperidin-4-yl)benzamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,6-dichloro-N-((3S,4S)-3-fluoro-1-isopropylpiperidin-4-yl)benzamide
• 英文别名: 2,6-dichloro-N-[(3S,4S)-3-fluoro-1-propan-2-ylpiperidin-4-yl]benzamide
• 化学式: C₁₅H₁₉Cl₂FN₂O
• 分子量: 333.233
• InChiKey: GTUHXXVOMDJMHH-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (3S,4S)-3-fluoro-1-propan-2-ylpiperidin-4-amine 、 2,6-二氯苯甲酰氯 以 1,4-二氧六环 为溶剂， 以41%的产率得到2,6-dichloro-N-((3S,4S)-3-fluoro-1-isopropylpiperidin-4-yl)benzamide
  参考文献：
  名称：

  Optimization of 4-Aminopiperidines as Inhibitors of Influenza A Viral Entry That Are Synergistic with Oseltamivir

  摘要：

  Vaccination is the most prevalent prophylactic means for controlling seasonal influenza infections. However, an effective vaccine usually takes at least 6 months to develop for the circulating strains. Therefore, new therapeutic options are needed for the acute treatment of influenza infections to control this virus and prevent epidemics/pandemics from developing. We have discovered fast-acting, orally bioavailable acylated 4-aminopiperidines with an effective mechanism of action targeting viral hemagglutinin (HA). Our data show that these compounds are potent entry inhibitors of influenza A viruses. We present docking studies that suggest an HA binding site for these inhibitors on H5N1. Compound 16 displayed a significant decrease of viral titer when evaluated in the infectious assays with influenza virus H1N1 (A/Puerto Rico/8/1934) or H5N1 (A/Vietnam/1203/2004) strains and the oseltamivir-resistant strain with the most common H274Y mutation. In addition, compound 16 showed significant synergistic activity with oseltamivir in vitro.

  DOI：

  10.1021/acs.jmedchem.9b01900

文献信息

• Optimization of 4-Aminopiperidines as Inhibitors of Influenza A Viral Entry That Are Synergistic with Oseltamivir
  作者：Irina N. Gaisina、Norton P. Peet、Han Cheng、Ping Li、Ruikun Du、Qinghua Cui、Kevin Furlong、Balaji Manicassamy、Michael Caffrey、Gregory R. J. Thatcher、Lijun Rong

  DOI：10.1021/acs.jmedchem.9b01900

  日期：2020.3.26

  Vaccination is the most prevalent prophylactic means for controlling seasonal influenza infections. However, an effective vaccine usually takes at least 6 months to develop for the circulating strains. Therefore, new therapeutic options are needed for the acute treatment of influenza infections to control this virus and prevent epidemics/pandemics from developing. We have discovered fast-acting, orally bioavailable acylated 4-aminopiperidines with an effective mechanism of action targeting viral hemagglutinin (HA). Our data show that these compounds are potent entry inhibitors of influenza A viruses. We present docking studies that suggest an HA binding site for these inhibitors on H5N1. Compound 16 displayed a significant decrease of viral titer when evaluated in the infectious assays with influenza virus H1N1 (A/Puerto Rico/8/1934) or H5N1 (A/Vietnam/1203/2004) strains and the oseltamivir-resistant strain with the most common H274Y mutation. In addition, compound 16 showed significant synergistic activity with oseltamivir in vitro.