4-(2-bromophenoxy)aniline | 57688-14-9

• 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: 4-(2-bromophenoxy)aniline
• CAS: 57688-14-9
• 化学式: C₁₂H₁₀BrNO
• 分子量: 264.121
• InChiKey: LIZVXEHACJOPPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(2-bromophenoxy)aniline 在 sodium hydroxide 作用下， 以 溶剂黄146 为溶剂， 反应 13.0h， 生成 6-(2-bromophenoxy)-2,3-dihydro-4(1H)-quinolinone
  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：

  2-溴-4'-硝基二苯醚 在 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 16.0h， 以90%的产率得到4-(2-bromophenoxy)aniline
  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

• Synthesis, biochemical evaluation and computational simulations of new cytochrome bc1 complex inhibitors based on N-(4-aryloxyphenyl) phthalimides
  作者：Hua Cheng、Yan Fu、Qing Chang、Ni Zhang、Mengwei Bu、Yan Niu、Qiongyou Wu、Cheng Chen、Francis Verpoort

  DOI：10.1016/j.cclet.2018.10.008

  日期：2018.12

  or complex III) is an attractive target for the discovery of numerous pharmaceuticals and pesticides. In order to identify new lead structures for this target, a new series of molecules, N-(4-aryloxyphenyl)phthalimides, were designed and synthesized in a straightforward manner. Our design strategy was to introduce a 4-aryloxyphenyl group, a fragment which exhibited promising bc1 complex-inhibiting

  摘要细胞色素bc1复合物（bc1复合物或复合物III）是发现众多药物和农药的诱人靶标。为了确定用于该靶标的新的铅结构，以简单的方式设计并合成了一系列新的分子N-（4-芳氧基苯基）邻苯二甲酰亚胺。我们的设计策略是将有价值的N-芳基邻苯二甲酰亚胺骨架的芳基引入一个4-芳基氧基苯基基团，该片段表现出有希望的bc1络合物抑制特性。之后，对新合成的化合物进行了生化评估，结果表明几种化合物对琥珀酸-细胞色素还原酶（SCR，线粒体复合物II和bc1复合物的混合物）具有良好的活性。进一步的研究证实3e'，本文中的一种代表性化合物被鉴定为bc1复合物的抑制剂。此外，还进行了计算模拟以更好地理解3e'与酶复合物的结合，这表明3e'应与bc1复合物的Qo位点结合。因此，我们认为本文可以为其他bc1复杂抑制剂的合成和发现提供坚实的平台。
• Discovery and optimization of 4-anilinoquinazoline derivatives spanning ATP binding site and allosteric site as effective EGFR-C797S inhibitors
  作者：Dou Dou、Jie Wang、Yunjin Qiao、Gulinuer Wumaier、Wenjie Sha、Wenjie Li、Wenyi Mei、Tingyuan Yang、Chen Zhang、Huan He、Caolin Wang、Linna Chu、Baihui Sun、Rongrong Su、Xiangyu Ma、Mengdie Gong、Lijuan Xie、Wenzhe Jiang、Yanyan Diao、Lili Zhu、Zhenjiang Zhao、Zhuo Chen、Yufang Xu、Shengqing Li、Honglin Li

  DOI：10.1016/j.ejmech.2022.114856

  日期：2022.12

  drug target for the treatment of non-small cell lung cancer (NSCLC). However, a tertiary point mutation (C797S) at the ATP binding pocket of the EGFR induces resistance to the third-generation EGFR inhibitors, due to the loss of covalent interaction with Cys797. Here, we designed a series of 4-anilinoquinazoline derivatives that simultaneously occupied the ATP binding pocket and the allosteric site

  表皮生长因子受体 (EGFR) 是治疗非小细胞肺癌 (NSCLC) 的有效药物靶点。然而，由于与 Cys797 的共价相互作用丧失，EGFR 的 ATP 结合口袋处的三级点突变 (C797S) 诱导了对第三代 EGFR 抑制剂的耐药性。在这里，我们设计了一系列同时占据 ATP 结合口袋和变构位点的 4-苯胺基喹唑啉衍生物。新合成的化合物对 EGFR-C797S 抗性突变显示出高效力。其中，化合物14d对 BaF3-EGFR L858R/T790M/C797S (IC 50  = 0.75 μM) 和 BaF3-EGFR 19del/T790M/C797S (IC 50 = 0.09 μM) 细胞。此外，14d在 BaF3-EGFR 19del/T790M/C797S细胞中以剂量依赖的方式对 EGFR 及其下游信号通路产生明显的抑制活性。最后，14d显着抑制 BaF3-EGFR 19del/
• Synthesis of new 4-aryloxy-N-arylanilines and their inhibitory activities against succinate-cytochrome c reductase
  作者：Hua Cheng、Wei Song、Ren Nie、Yu-Xia Wang、Hui-Lian Li、Xiang-Sheng Jiang、Jun-Jun Wu、Cheng Chen、Qiong-You Wu

  DOI：10.1016/j.bmcl.2018.03.014

  日期：2018.5

  Succinate-cytochrome c reductase (SCR) is composed of a mixture of mitochondrial complex II (succinate-ubiquinone oxidoreductase) and complex III (cytochrome bc(1) complex). Meanwhile, complexes II and III are two promising targets of numerous antibiotics and fungicides. With an aim to identify new lead structures for SCR, complex II or III, a new series of 4-aryloxy-N-arylanilines were synthesized by introducing a 4-aryloxy phenyl group as one of the aryl groups in diaryl amines. With the economic Cu(OAc)(2).H2O as the optimal copper promoter, a simple and facile protocol was utilized to afford 24 target products in 56-93% yields. Furthermore, extensive screening results suggested variable inhibitory activities of these compounds against SCR. Exceptionally, compounds 7k-7n showed excellent inhibition potency with their IC50 values in the nanomolar range, demonstrating higher potency than the commercial controls (penthiopyrad and azoxystrobin) by over one order of magnitude. (C) 2018 Elsevier Ltd. All rights reserved.
• US4056553A
  申请人：——

  公开号：US4056553A

  公开（公告）日：1977-11-01
• 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.