2,3,5,6-tetrafluoro-4-[(2-hydroxyethyl)sulfonyl] benzenesulfonamide | 1428673-21-5

• 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-hydroxyethyl)sulfonyl] benzenesulfonamide
• 英文别名: 2,3,5,6-tetrafluoro-4[(2-hydroxyethyl)sulfonyl]benzenesulfonamide；VD10-35；2,3,5,6-Tetrafluoro-4-[(2-Hydroxyethyl)sulfonyl]benzenesulfonamide；2,3,5,6-tetrafluoro-4-(2-hydroxyethylsulfonyl)benzenesulfonamide
• CAS: 1428673-21-5
• 化学式: C₈H₇F₄NO₅S₂
• 分子量: 337.273
• InChiKey: WZGGLNWNBUCLIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2,3,5,6-tetrafluoro-4-[(2-hydroxyethyl)sulfonyl] benzenesulfonamide 、 3,4-二甲氧基苄胺 以 二甲基亚砜 为溶剂， 反应 120.0h， 以53%的产率得到3,5-bis[(3,4-dimethoxybenzyl)amino]-2,6-difluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide
  参考文献：
  名称：

  [EN] FLUORINATED BENZENESULFONAMIDES AS INHIBITORS OF CARBONIC ANHYDRASE
  [FR] BENZÈNESULFONAMIDES FLUORÉS À UTILISER EN TANT QU'INHIBITEURS D'ANHYDRASE CARBONIQUE

  摘要：

  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。

  公开号：

  WO2014062044A1
• 作为产物：
  描述：

  2,3,4,5,6-五氟苯磺酰氯 在 ammonium hydroxide 、 双氧水 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 30.5h， 生成 2,3,5,6-tetrafluoro-4-[(2-hydroxyethyl)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

• Discovery and Characterization of Novel Selective Inhibitors of Carbonic Anhydrase IX
  作者：Virginija Dudutienė、Jurgita Matulienė、Alexey Smirnov、David D. Timm、Asta Zubrienė、Lina Baranauskienė、Vaida Morku̅naitė、Joana Smirnovienė、Vilma Michailovienė、Vaida Juozapaitienė、Aurelija Mickevičiu̅tė、Justina Kazokaitė、Sandra Bakšytė、Aistė Kasiliauskaitė、Jelena Jachno、Jurgita Revuckienė、Miglė Kišonaitė、Vilma Pilipuitytė、Eglė Ivanauskaitė、Goda Milinavičiu̅tė、Vytautas Smirnovas、Vilma Petrikaitė、Visvaldas Kairys、Vytautas Petrauskas、Povilas Norvaišas、Darius Lingė、Paulius Gibieža、Edita Čapkauskaitė、Audrius Zakšauskas、Egidijus Kazlauskas、Elena Manakova、Saulius Gražulis、John E. Ladbury、Daumantas Matulis

  DOI：10.1021/jm501003k

  日期：2014.11.26

  Human carbonic anhydrase IX (CA IX) is highly expressed in tumor tissues, and its selective inhibition provides a potential target for the treatment of numerous cancers. Development of potent, highly selective inhibitors against this target remains an unmet need in anticancer therapeutics. A series of fluorinated benzenesulfonamides with substituents on the benzene ring was designed and synthesized

  人碳酸酐酶IX（CA IX）在肿瘤组织中高度表达，其选择性抑制为许多癌症的治疗提供了潜在的靶标。针对该靶标的有效，高选择性抑制剂的开发仍然是抗癌疗法中尚未满足的需求。设计并合成了一系列在苯环上带有取代基的氟化苯磺酰胺。这些中的几个表现出对CA IX的高度有效和选择性的抑制作用。三个氟原子通过吸电子和降低p K a显着增加了亲和力苯磺酰胺基团。如化合物与嵌合CA IX的共晶体结构所示，庞大的邻位取代基（例如环辛基或什至环十二烷基）适合CA IX活性位点的疏水口袋，而不适合CA II。人细胞中重组人CA IX催化结构域的最强抑制剂达到了50 pM的亲和力。但是，高亲和力降低了选择性。对CA IX最具选择性的化合物表现出10 nM的亲和力。在亲和力和选择性之间显示出最佳平衡的化合物，其亲和力为1 nM。这项工作中描述的抑制剂为靶向CA IX的新型抗癌疗法提供了基础。
• 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。
• CA IX—NIR dyes and their uses
  申请人：On Target Laboratories, LLC

  公开号：US10557854B2

  公开（公告）日：2020-02-11

  The present disclosure relates to compounds that are useful as near-infrared fluorescence probes, wherein the compounds include i) a ligand that binds to the active site of carbonic anhydrase, ii) a dye molecule, and iii) a linker molecule that comprises an amino acid, amide, ureido, or polyethylene glycol derivative thereof. The disclosure further describes methods and compositions for making and using the compounds, methods incorporating the compounds, and kits incorporating the compounds.

  本公开涉及可用作近红外荧光探针的化合物，其中化合物包括 i) 与碳酸酐酶活性位点结合的配体；ii) 染料分子；iii) 由氨基酸、酰胺、脲基或聚乙二醇衍生物组成的连接分子。本公开进一步描述了制造和使用这些化合物的方法和组合物、包含这些化合物的方法以及包含这些化合物的试剂盒。
• CA IX-TARGET NIR DYES AND THEIR USES
  申请人：On Target Laboratories, LLC

  公开号：EP3430383A1

  公开（公告）日：2019-01-23
• CA IX - NIR DYES AND THEIR USES
  申请人：On Target Laboratories, LLC

  公开号：US20170285040A1

  公开（公告）日：2017-10-05

  The present disclosure relates to compounds that are useful as near-infrared fluorescence probes, wherein the compounds include i) a ligand that binds to the active site of carbonic anhydrase, ii) a dye molecule, and iii) a linker molecule that comprises an amino acid, amide, ureido, or polyethylene glycol derivative thereof. The disclosure further describes methods and compositions for making and using the compounds, methods incorporating the compounds, and kits incorporating the compounds.