ethyl 2-amino-5-(2-bromophenoxy)benzoate | 1315379-64-6

• 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: ethyl 2-amino-5-(2-bromophenoxy)benzoate
• CAS: 1315379-64-6
• 化学式: C₁₅H₁₄BrNO₃
• 分子量: 336.185
• InChiKey: HJVXLVGHOKETSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-amino-5-(2-bromophenoxy)benzoate 在 吡啶 、 sodium ethanolate 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 52.0h， 生成 6-(2-bromophenoxy)-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide
  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
• 作为产物：
  描述：

  ethyl 5-(2-bromophenoxy)-2-nitrobenzoate 在 氢气 作用下， 以 乙酸乙酯 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 5.0h， 以83%的产率得到ethyl 2-amino-5-(2-bromophenoxy)benzoate
  参考文献：
  名称：

  N-苯甲酰基-N-甲基磺酰基邻氨基苯甲酸酯：出人意料的环化反应生成 4-烷氧基-2,1-苯并噻嗪

  摘要：

  4-烷氧基-1H-2,1-苯并噻嗪 2,2-二氧化物衍生物的合成是通过 N-苯甲酰基-N-甲基磺酰氨基苯甲酸酯的意外碱介导环化实现的。已经假设了涉及亚砜物种的反应机制。获得的 4-烷氧基衍生物可以在 N-1 位进一步官能化，从而制备不对称的 N,O 二取代的 1H-2,1-苯并噻嗪 2,2-二氧化物。

  DOI：

  10.3998/ark.5550190.0012.912

文献信息

• N-Benzoyl-N-methylsulfonyl anthranilates: unexpected cyclization reaction to 4-alkoxy-2,1-benzothiazines
  作者：Giuseppe Manfroni、Francesco Meschini、Ferdinando Costantino、Oriana Tabarrini、Violetta Cecchetti

  DOI：10.3998/ark.5550190.0012.912

  日期：——

  The synthesis of 4-alkoxy-1H-2,1-benzothiazine 2,2-dioxide derivatives was achieved through an unexpected base-mediated cyclization of N-benzoyl-N-methylsulfonylanthranilates. A reaction mechanism involving the sulfene species has been postulated. The obtained 4-alkoxy derivatives can be further functionalized at the N-1 position allowing unsymmetrically N,Odisubstituted 1H-2,1-benzothiazines 2,2-dioxide

  4-烷氧基-1H-2,1-苯并噻嗪 2,2-二氧化物衍生物的合成是通过 N-苯甲酰基-N-甲基磺酰氨基苯甲酸酯的意外碱介导环化实现的。已经假设了涉及亚砜物种的反应机制。获得的 4-烷氧基衍生物可以在 N-1 位进一步官能化，从而制备不对称的 N,O 二取代的 1H-2,1-苯并噻嗪 2,2-二氧化物。
• 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.