2,3,5,6-tetrafluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide | 1428673-33-9

• 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: 2,3,5,6-tetrafluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide
• 英文别名: 2,3,5,6-Tetrafluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide；2,3,5,6-tetrafluoro-4-(2-phenylethylsulfonyl)benzenesulfonamide
• CAS: 1428673-33-9
• 化学式: C₁₄H₁₁F₄NO₄S₂
• 分子量: 397.371
• InChiKey: XJNXCEJSOGKOSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  金刚烷胺 、 2,3,5,6-tetrafluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 120.0h， 以8%的产率得到3-(1-adamantylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]-benzenesulfonamide
  参考文献：
  名称：

  氟化苯磺酰胺的功能化及其对碳酸酐酶的抑制作用

  摘要：

  设计，合成和评估了取代的三氟和四氟苯磺酰胺，作为高亲和力和同工型选择性碳酸酐酶（CA）抑制剂。通过荧光热移测定，等温滴定量热法和停止流动的CO 2来确定它们对重组人CA I，II，VA，VI，VII，XII和XIII催化域的结合亲和力水化测定。在2、3和4位上取代基的变化产生具有宽范围结合亲和力和同工型选择性的化合物。几种2,4-取代的-3,5,6-三氟苯磺酰胺是有效的CA XIII抑制剂，对脱靶CA I和CA II具有高选择性。3,4-二取代-2,5,6-三氟苯磺酰胺与CA的亲和力高于2,4-二取代-3,5,6-三氟苯磺酰胺。发现许多此类氟化苯磺酰胺是CA II，CA VII，与肿瘤相关的CA IX和CA XII和CA XIII的纳摩尔抑制剂。结合在几种CA同工型活性位点上的抑制剂的X射线晶体结构为抑制剂结合亲和力和选择性提供了结构-活性关系信息。

  DOI：

  10.1002/cmdc.201402490
• 作为产物：
  描述：

  2,3,4,5,6-五氟苯磺酰氯 在 chromium(VI) oxide 、 ammonium hydroxide 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 水 为溶剂， 反应 12.5h， 生成 2,3,5,6-tetrafluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide
  参考文献：
  名称：

  4-Substituted-2,3,5,6-tetrafluorobenzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII

  摘要：

  A series of 4-substituted-2,3,5,6-tetrafluorobenezenesulfonamides were synthesized and their binding potencies as inhibitors of recombinant human carbonic anhydrase isozymes I, II, VII, XII, and XIII were determined by the thermal shift assay, isothermal titration calorimetry, and stop-flow CO2 hydration assay. All fluorinated benzenesulfonamides exhibited nanomolar binding potency toward tested CAs and fluorinated benzenesulfonamides posessed higher binding potency than non-fluorinated compounds. The crystal structures of 4-[(4,6-dimethylpyrimidin-2-yl)thio]-2,3,5,6-tetrafluorobenzenesulfonamide in complex with CA II and CA XII, and 2,3,5,6-tetrafluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide in complex with CA XIII were determined. The observed dissociation constants for several fluorinated compounds reached subnanomolar range for CA I isozyme. The affinity and the selectivity of the compounds towards tested isozymes are presented. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.008

文献信息

• [EN] FLUORINATED BENZENESULFONAMIDES AS INHIBITORS OF CARBONIC ANHYDRASE<br/>[FR] BENZÈNESULFONAMIDES FLUORÉS À UTILISER EN TANT QU'INHIBITEURS D'ANHYDRASE CARBONIQUE
  申请人：UNIV VILNIUS

  公开号：WO2014062044A1

  公开（公告）日：2014-04-24

  Invention is related to novel compounds - fluorinated benzenesulfonamides of general formula (I). The compounds can be used in biomedicine as active ingredients in pharmaceutical formulations, because they inhibit enzymes which participate in disease progression. ˙

  本发明涉及一种新型化合物 - 一般式(I)的氟化苯磺酰胺。这些化合物可用于生物医学中作为药物配方的活性成分，因为它们抑制参与疾病进展的酶。
• FLUORINATED BENZENESULFONAMIDES AS INHIBITORS OF CARBONIC ANHYDRASE
  申请人：VILNIUS UNIVERSITY

  公开号：US20150266900A1

  公开（公告）日：2015-09-24

  Novel fluorinated benzenesulfonamides compounds of general formula (I) can be used in biomedicine as active ingredients in pharmaceutical formulations, because they inhibit enzymes which participate in disease progression.

  通式（I）的新型氟代苯磺酰胺化合物可以作为药物制剂中的活性成分在生物医学中使用，因为它们可以抑制参与疾病进展的酶。
• US9725467B2
  申请人：——

  公开号：US9725467B2

  公开（公告）日：2017-08-08
• 4-Substituted-2,3,5,6-tetrafluorobenzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII
  作者：Virginija Dudutienė、Asta Zubrienė、Alexey Smirnov、Joana Gylytė、David Timm、Elena Manakova、Saulius Gražulis、Daumantas Matulis

  DOI：10.1016/j.bmc.2013.01.008

  日期：2013.4

  A series of 4-substituted-2,3,5,6-tetrafluorobenezenesulfonamides were synthesized and their binding potencies as inhibitors of recombinant human carbonic anhydrase isozymes I, II, VII, XII, and XIII were determined by the thermal shift assay, isothermal titration calorimetry, and stop-flow CO2 hydration assay. All fluorinated benzenesulfonamides exhibited nanomolar binding potency toward tested CAs and fluorinated benzenesulfonamides posessed higher binding potency than non-fluorinated compounds. The crystal structures of 4-[(4,6-dimethylpyrimidin-2-yl)thio]-2,3,5,6-tetrafluorobenzenesulfonamide in complex with CA II and CA XII, and 2,3,5,6-tetrafluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide in complex with CA XIII were determined. The observed dissociation constants for several fluorinated compounds reached subnanomolar range for CA I isozyme. The affinity and the selectivity of the compounds towards tested isozymes are presented. (C) 2013 Elsevier Ltd. All rights reserved.
• Functionalization of Fluorinated Benzenesulfonamides and Their Inhibitory Properties toward Carbonic Anhydrases
  作者：Virginija Dudutienė、Asta Zubrienė、Alexey Smirnov、David D. Timm、Joana Smirnovienė、Justina Kazokaitė、Vilma Michailovienė、Audrius Zakšauskas、Elena Manakova、Saulius Gražulis、Daumantas Matulis

  DOI：10.1002/cmdc.201402490

  日期：2015.4

  over off‐target CA I and CA II. 3,4‐Disubstituted‐2,5,6‐trifluorobenzenesulfonamides bound CAs with higher affinity than 2,4‐disubstituted‐3,5,6‐trifluorobenzenesulfonamides. Many such fluorinated benzenesulfonamides were found to be nanomolar inhibitors of CA II, CA VII, tumor‐associated CA IX and CA XII, and CA XIII. X‐ray crystal structures of inhibitors bound in the active sites of several CA isoforms

  设计，合成和评估了取代的三氟和四氟苯磺酰胺，作为高亲和力和同工型选择性碳酸酐酶（CA）抑制剂。通过荧光热移测定，等温滴定量热法和停止流动的CO 2来确定它们对重组人CA I，II，VA，VI，VII，XII和XIII催化域的结合亲和力水化测定。在2、3和4位上取代基的变化产生具有宽范围结合亲和力和同工型选择性的化合物。几种2,4-取代的-3,5,6-三氟苯磺酰胺是有效的CA XIII抑制剂，对脱靶CA I和CA II具有高选择性。3,4-二取代-2,5,6-三氟苯磺酰胺与CA的亲和力高于2,4-二取代-3,5,6-三氟苯磺酰胺。发现许多此类氟化苯磺酰胺是CA II，CA VII，与肿瘤相关的CA IX和CA XII和CA XIII的纳摩尔抑制剂。结合在几种CA同工型活性位点上的抑制剂的X射线晶体结构为抑制剂结合亲和力和选择性提供了结构-活性关系信息。