4-nitro-N-(3-(trifluoromethyl)phenyl)benzenesulfonamide | 2927-97-1

• 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-nitro-N-(3-(trifluoromethyl)phenyl)benzenesulfonamide
• 英文别名: 4-Nitro-benzol-sulfonsaeure-(1)-<3-trifluormethylanilid>；4-Nitro-benzol-sulfonsaeure-(1)-(3-trifluormethylanilid)；4-nitro-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide
• CAS: 2927-97-1
• 化学式: C₁₃H₉F₃N₂O₄S
• mdl: MFCD00395309
• 分子量: 346.287
• InChiKey: KCDRKUYDDXPNQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-nitro-N-(3-(trifluoromethyl)phenyl)benzenesulfonamide 在 palladium on activated charcoal 、 氢气 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 20.0~120.0 ℃ 、413.7 kPa 条件下， 反应 34.25h， 生成 N-(furan-2-ylmethyl)-4-oxo-6-(N-(3-(trifluoromethyl)phenyl)sulfamoyl)-1,4-dihydroquinoline-3-carboxamide
  参考文献：
  名称：

  4-Oxo-1,4-dihydro-quinoline-3-carboxamides as BACE-1 inhibitors: Synthesis, biological evaluation and docking studies

  摘要：

  In this work, we report a series of new 4-oxo-1,4-dihydro-quinoline-3-carboxamide derivatives as,beta-secretase (BACE-1) inhibitors. Supported by docking study, a small library of derivatives were designed, synthesized and biologically evaluated in vitro. The studies revealed that the most potent analog 14e (IC50 = 1.89 mu M) with low cellular cytotoxicity and high predicted blood brain barrier permeability, could serve as a good structure for further modification.(c) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.04.025
• 作为产物：
  描述：

  间氨基三氟甲苯 、 对硝基苯磺酰氯 以 二氯甲烷 为溶剂， 生成 4-nitro-N-(3-(trifluoromethyl)phenyl)benzenesulfonamide
  参考文献：
  名称：

  Structure-Guided Design of Potent Diazobenzene Inhibitors for the BET Bromodomains

  摘要：

  BRD4, characterized by two acetyl-lysine binding bromodomains and an extra-terminal (ET) domain, is a key chromatin organizer that directs gene activation in chromatin through transcription factor recruitment, enhancer assembly, and pause release of the RNA polymerase II complex for transcription elongation. BRD4 has been recently validated as a new epigenetic drug target for cancer and inflammation. Our current knowledge of the functional differences of the two bromodomains of BRD4, however, is limited and is hindered by the lack of selective inhibitors. Here, we report our structure-guided development of diazobenzene-based small-molecule inhibitors for the BRD4 bromodomains that have over 90% sequence identity at the acetyl-lysine binding site. Our lead compound, MS436, through a set of water-mediated interactions, exhibits low nanomolar affinity (estimated Ki of 30-50 nM), with preference for the first bromodomain over the second. We demonstrated that MS436 effectively inhibits BRD4 activity in NF-κB-directed production of nitric oxide and proinflammatory cytokine interleukin-6 in murine macrophages. MS436 represents a new class of bromodomain inhibitors and will facilitate further investigation of the biological functions of the two bromodomains of BRD4 in gene expression.

  DOI：

  10.1021/jm401334s

文献信息

• Base‐Promoted Michael Addition/Smiles Rearrangement/ <i>N</i> ‐Arylation Cascade: One‐Step Synthesis of 1,2,3‐Trisubstituted 4‐Quinolones from Ynones and Sulfonamides
  作者：Jing Liu、Dan Ba、Weiwei Lv、Yanhui Chen、Zemin Zhao、Guolin Cheng

  DOI：10.1002/adsc.201900960

  日期：2020.1.7

  synthesize 1,2,3‐trisubstituted 4‐quinolones from readily available ynones and sulfonamides was developed. The construction of one C−C bond and two C−N bonds via cleavage of one N−S, one C−S, and one C−X (X=F, Cl, Br, O) bond is achieved under transition‐metal‐free conditions in one step. This transformation generates 1 equiv. of sulfur dioxide and 1 equiv. of hydrogen halide as the byproducts. The broad substrate

  已开发了一种通用，实用且环保的方案，可以从容易获得的炔酮和磺酰胺中合成1,2,3-三取代的4-喹诺酮。在过渡金属的作用下，通过裂解一个N-S，一个C-S和一个C-X（X = F，Cl，Br，O）键，可以构建一个C-C键和两个C-N键。一步就能达到无条件。此变换生成1个当量。二氧化硫和1当量 卤化氢作为副产物。1,2,3-三取代的4-喹诺酮类化合物的52个实例证明了广泛的底物范围和官能团耐受性。初步的机理研究支持顺序的迈克尔加成/微笑重排/ N芳基化反应途径。
• Traceless N‐Polyfluoroalkylation of Weakly Nucleophilic Nitrogen Containing Compounds
  作者：Laura Santos、Florian Audet、Morgan Donnard、Armen Panossian、Jean-Pierre Vors、David Bernier、Sergii Pazenok、Frederic R. Leroux

  DOI：10.1002/chem.202300792

  日期：——

  the high cost, toxicity or environmental impact of commonly used polyfluoroalkylation reagents. We report the sulfuryl fluoride (SO2F2)-mediated N-polyfluoroalkylation of weakly nucleophilic nitrogen compounds from readily available fluorinated alcohols. This method opens access to a variety of N-polyfluoroalkylated building blocks that are highly valuable for life science applications.

  由于常用多氟烷基化试剂的高成本、毒性或环境影响， N-多氟烷基化反应具有挑战性。我们报告了硫酰氟 (SO 2 F 2 ) 介导的弱亲核氮化合物的N -多氟烷基化，这些化合物来自现成的氟化醇。该方法开启了对各种N-多氟烷基化构建块的访问，这些构建块对生命科学应用具有很高的价值。
• Structure-Guided Design of Potent Diazobenzene Inhibitors for the BET Bromodomains
  作者：Guangtao Zhang、Alexander N. Plotnikov、Elena Rusinova、Tong Shen、Keita Morohashi、Jennifer Joshua、Lei Zeng、Shiraz Mujtaba、Michael Ohlmeyer、Ming-Ming Zhou

  DOI：10.1021/jm401334s

  日期：2013.11.27

  BRD4, characterized by two acetyl-lysine binding bromodomains and an extra-terminal (ET) domain, is a key chromatin organizer that directs gene activation in chromatin through transcription factor recruitment, enhancer assembly, and pause release of the RNA polymerase II complex for transcription elongation. BRD4 has been recently validated as a new epigenetic drug target for cancer and inflammation. Our current knowledge of the functional differences of the two bromodomains of BRD4, however, is limited and is hindered by the lack of selective inhibitors. Here, we report our structure-guided development of diazobenzene-based small-molecule inhibitors for the BRD4 bromodomains that have over 90% sequence identity at the acetyl-lysine binding site. Our lead compound, MS436, through a set of water-mediated interactions, exhibits low nanomolar affinity (estimated Ki of 30-50 nM), with preference for the first bromodomain over the second. We demonstrated that MS436 effectively inhibits BRD4 activity in NF-κB-directed production of nitric oxide and proinflammatory cytokine interleukin-6 in murine macrophages. MS436 represents a new class of bromodomain inhibitors and will facilitate further investigation of the biological functions of the two bromodomains of BRD4 in gene expression.
• 4-Oxo-1,4-dihydro-quinoline-3-carboxamides as BACE-1 inhibitors: Synthesis, biological evaluation and docking studies
  作者：Peng Liu、Yan Niu、Chao Wang、Qi Sun、Yaya Zhai、Jiapei Yu、Jing Sun、Fengrong Xu、Gang Yan、Wenjie Huang、Lei Liang、Ping Xu

  DOI：10.1016/j.ejmech.2014.04.025

  日期：2014.5

  In this work, we report a series of new 4-oxo-1,4-dihydro-quinoline-3-carboxamide derivatives as,beta-secretase (BACE-1) inhibitors. Supported by docking study, a small library of derivatives were designed, synthesized and biologically evaluated in vitro. The studies revealed that the most potent analog 14e (IC50 = 1.89 mu M) with low cellular cytotoxicity and high predicted blood brain barrier permeability, could serve as a good structure for further modification.(c) 2014 Elsevier Masson SAS. All rights reserved.