6-(3-tert-butylphenoxy)-2,2-dioxido-1H-2,1-benzothiazin-4-yl benzoate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-(3-tert-butylphenoxy)-2,2-dioxido-1H-2,1-benzothiazin-4-yl benzoate
• 英文别名: [6-(3-tert-butylphenoxy)-2,2-dioxo-1H-2lambda6,1-benzothiazin-4-yl] benzoate；[6-(3-tert-butylphenoxy)-2,2-dioxo-1H-2λ6,1-benzothiazin-4-yl] benzoate
• 化学式: C₂₅H₂₃NO₅S
• 分子量: 449.527
• InChiKey: UMZMLZXBFKIEFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  90.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-叔丁基苯酚 在 吡啶 、 氢气 、 sodium ethanolate 、 potassium carbonate 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 35.0h， 生成 6-(3-tert-butylphenoxy)-2,2-dioxido-1H-2,1-benzothiazin-4-yl benzoate
  参考文献：
  名称：

  Functionalized 2,1-benzothiazine 2,2-dioxides as new inhibitors of Dengue NS5 RNA-dependent RNA polymerase

  摘要：

  Over recent years, many RNA viruses have been "re-discovered", including life-threatening flaviviruses, such as Dengue, Zika, and several encephalitis viruses. Since no specific inhibitors are currently available to treat these infections, there is a pressing need for new therapeutics. Among the flaviviral proteins, NS5 RNA-dependent RNA polymerase (RdRp) represents a validated target being essential for viral replication and it has no human analog. To date, few NS5 RdRp inhibitor chemotypes have been reported and no inhibitors are currently in clinical development. In this context, after an in vitro screening against Dengue 3 NS5 RdRp of our in-house HCV NS5B inhibitors focused library, we found that 2,1-benzothiazine 2,2-dioxides are promising non-nucleoside inhibitors of flaviviral RdRp with compounds 8 and 10 showing IC50 of 0.6 and 0.9 mu M, respectively. Preliminary structure-activity relationships indicated a key role for the C-4 benzoyl group and the importance of a properly functionalized C-6 phenoxy moiety to modulate potency. Compound 8 acts as non-competitive inhibitor and its proposed pose in the so-called N pocket of the RdRp thumb domain allowed to explain the key contribution of the benzoyl and the phenoxy moieties for the ligand binding. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.10.064

文献信息

• Functionalized 2,1-benzothiazine 2,2-dioxides as new inhibitors of Dengue NS5 RNA-dependent RNA polymerase
  作者：Rolando Cannalire、Delia Tarantino、Andrea Astolfi、Maria Letizia Barreca、Stefano Sabatini、Serena Massari、Oriana Tabarrini、Mario Milani、Gilles Querat、Eloise Mastrangelo、Giuseppe Manfroni、Violetta Cecchetti

  DOI：10.1016/j.ejmech.2017.10.064

  日期：2018.1

  Over recent years, many RNA viruses have been "re-discovered", including life-threatening flaviviruses, such as Dengue, Zika, and several encephalitis viruses. Since no specific inhibitors are currently available to treat these infections, there is a pressing need for new therapeutics. Among the flaviviral proteins, NS5 RNA-dependent RNA polymerase (RdRp) represents a validated target being essential for viral replication and it has no human analog. To date, few NS5 RdRp inhibitor chemotypes have been reported and no inhibitors are currently in clinical development. In this context, after an in vitro screening against Dengue 3 NS5 RdRp of our in-house HCV NS5B inhibitors focused library, we found that 2,1-benzothiazine 2,2-dioxides are promising non-nucleoside inhibitors of flaviviral RdRp with compounds 8 and 10 showing IC50 of 0.6 and 0.9 mu M, respectively. Preliminary structure-activity relationships indicated a key role for the C-4 benzoyl group and the importance of a properly functionalized C-6 phenoxy moiety to modulate potency. Compound 8 acts as non-competitive inhibitor and its proposed pose in the so-called N pocket of the RdRp thumb domain allowed to explain the key contribution of the benzoyl and the phenoxy moieties for the ligand binding. (C) 2017 Elsevier Masson SAS. All rights reserved.