4-isothiocyanato-N-(4-sulfamoylbenzyl)benzenesulfonamide | 853885-96-8

• 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-isothiocyanato-N-(4-sulfamoylbenzyl)benzenesulfonamide
• CAS: 853885-96-8
• 化学式: C₁₄H₁₃N₃O₄S₃
• 分子量: 383.473
• InChiKey: LZDLZGPIBBFSSF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.55
• 重原子数：
  24.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  118.69
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  4-isothiocyanato-N-(4-sulfamoylbenzyl)benzenesulfonamide 、 1-氨基-4-甲基哌嗪 在 三乙胺 作用下， 生成
  参考文献：
  名称：

  碳酸酐酶抑制剂：胞嘧啶/肿瘤相关的碳酸酐酶同工酶I，II和IX的合成和抑制，以及掺入硫脲基-磺胺基支架的磺酰胺。

  摘要：

  肿瘤相关的跨膜碳酸酐酶（CA，EC 4.2.1.1）同工酶IX（CA IX）在低氧性肿瘤中过表达，并且似乎参与了肿瘤微环境的酸化，该过程与癌症的进展和不良的预后相关。可以通过用强效的磺酰胺/氨基磺酸CA抑制剂抑制酶来减少酸化作用。已经制备了一系列结合有硫脲基-磺酰苯胺基部分的芳族磺酰胺，并研究了其与人同工酶hCA IX的催化结构域的相互作用。合成中的关键中间体是通过使磺胺，高磺酰胺或4-氨基乙基苯磺酰胺与4-乙酰氨基-苯磺酰氯反应，然后脱乙酰基并与硫光气反应而获得的。使获得的异硫氰酸根合磺酰胺与脂族或芳族伯胺或肼反应，得到相应的硫脲。这些化合物中的某些显示出对同工酶I，II和IX的优异抑制特性，并且几种抑制剂还显示出对CA IX的抑制作用比对普遍存在的同工酶CA II的选择性。基于对在低氧肿瘤中过表达的CA同工酶的抑制作用，此类磺酰胺可能构成开发新型抗肿瘤疗法的有趣候选物。由于CA IX在

  DOI：

  10.1016/j.bmcl.2005.02.087
• 作为产物：
  描述：

  硫光气 、 4-(sulfanilylamino-methyl)-benzenesulfonic acid amide 在 氢气 作用下， 生成 4-isothiocyanato-N-(4-sulfamoylbenzyl)benzenesulfonamide
  参考文献：
  名称：

  碳酸酐酶抑制剂：胞嘧啶/肿瘤相关的碳酸酐酶同工酶I，II和IX的合成和抑制，以及掺入硫脲基-磺胺基支架的磺酰胺。

  摘要：

  肿瘤相关的跨膜碳酸酐酶（CA，EC 4.2.1.1）同工酶IX（CA IX）在低氧性肿瘤中过表达，并且似乎参与了肿瘤微环境的酸化，该过程与癌症的进展和不良的预后相关。可以通过用强效的磺酰胺/氨基磺酸CA抑制剂抑制酶来减少酸化作用。已经制备了一系列结合有硫脲基-磺酰苯胺基部分的芳族磺酰胺，并研究了其与人同工酶hCA IX的催化结构域的相互作用。合成中的关键中间体是通过使磺胺，高磺酰胺或4-氨基乙基苯磺酰胺与4-乙酰氨基-苯磺酰氯反应，然后脱乙酰基并与硫光气反应而获得的。使获得的异硫氰酸根合磺酰胺与脂族或芳族伯胺或肼反应，得到相应的硫脲。这些化合物中的某些显示出对同工酶I，II和IX的优异抑制特性，并且几种抑制剂还显示出对CA IX的抑制作用比对普遍存在的同工酶CA II的选择性。基于对在低氧肿瘤中过表达的CA同工酶的抑制作用，此类磺酰胺可能构成开发新型抗肿瘤疗法的有趣候选物。由于CA IX在

  DOI：

  10.1016/j.bmcl.2005.02.087

文献信息

• Carbonic anhydrase inhibitors. Inhibition of isoforms I, II, IV, VA, VII, IX, and XIV with sulfonamides incorporating fructopyranose–thioureido tails
  作者：Jean-Yves Winum、Anne Thiry、Khaled El Cheikh、Jean-Michel Dogné、Jean-Louis Montero、Daniela Vullo、Andrea Scozzafava、Bernard Masereel、Claudiu T. Supuran

  DOI：10.1016/j.bmcl.2007.03.008

  日期：2007.5

  slightly inhibited isoforms hCA IV and hCA VA. Only the sulfanilamide derivative showed efficient and selective inhibition of hCA IV (K(I) of 10nM). These derivatives also showed excellent hCA VII inhibitory activity (K(I)s of 10-79nM), being less efficient as inhibitors of the transmembrane isoforms hCA IX (K(I)s of 10-4500nM) and hCA XIV (K(I)s of 21-3500nM). Two of the new compounds showed anticonvulsant

  合成了一系列结合2,3：4,5-双-O-（异亚丙基）-β-d-果糖吡喃糖基-硫脲基部分的芳香族/杂环磺酰胺并测定了对锌酶碳酸酐酶的7种人同工型的抑制作用（hCA，EC 4.2.1.1）。新的衍生物表现为弱hCA I抑制剂（K（I）为9.4 -13.3microM），有效的hCA II抑制剂（K-I为6-750nM）和轻微抑制的亚型hCA IV和hCA VA。仅磺胺酰胺衍生物显示出对hCA IV的有效和选择性抑制（K（I）为10nM）。这些衍生物还显示出出色的hCA VII抑制活性（K（I）s为10​​-79nM），作为跨膜同工型hCA IX（K（I）s为10​​-4500nM）和hCA XIV（K（I ）（21-3500nM）。
• Carbonic anhydrase inhibitors: Design of spin-labeled sulfonamides incorporating TEMPO moieties as probes for cytosolic or transmembrane isozymes
  作者：Alessandro Cecchi、Laura Ciani、Jean-Yves Winum、Jean-Louis Montero、Andrea Scozzafava、Sandra Ristori、Claudiu T. Supuran

  DOI：10.1016/j.bmcl.2008.05.051

  日期：2008.6

  A series of spin-labeled sulfonamides incorporating TEMPO moieties were synthesized by a procedure involving the formation of a thiourea functionality between the benzenesulfonamide and free radical fragment of the molecules. The new compounds were tested as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and showed efficient inhibition of the physiologically relevant isozymes hCA II and hCA IX (hCA IX being predominantly found in tumors) and moderate to weak inhibitory activity against hCA I. Some derivatives were also selective for inhibiting the tumor-associated isoform over the cytosolic one CA II, and presented significant changes in their ESR signals when complexed to the enzyme active site, being interesting candidates for the investigation of hypoxic tumors overexpressing CA IX by ESR techniques, as well as for imaging/treatment purposes. (C) 2008 Elsevier Ltd. All rights reserved.
• Carbonic Anhydrase Inhibitors. Design of Fluorescent Sulfonamides as Probes of Tumor-Associated Carbonic Anhydrase IX That Inhibit Isozyme IX-Mediated Acidification of Hypoxic Tumors
  作者：Alessandro Cecchi、Alzbeta Hulikova、Jaromír Pastorek、Silvia Pastoreková、Andrea Scozzafava、Jean-Yves Winum、Jean-Louis Montero、Claudiu T. Supuran

  DOI：10.1021/jm0501073

  日期：2005.7.1

  Sulfonamides inhibit the catalytic activity of carbonic anhydrases (CAs, EC 4.2.1.1), enzymes participating in the regulation of acid-base balance and ion transport in many tissues. Carbonic anhydrase IX (CA IX), a transmembrane isoform with predominant association with tumors and limited distribution in normal tissues, is strongly overexpressed by hypoxia. Hypoxia increases the catalytic performance of CA IX contributing to microenvironmental acidosis, which influences cancer progression and treatment outcome. CA IX represents a target for detection and therapy of hypoxic tumors. Sulfonamide CA IX selective inhibitors accumulate only in hypoxic cells containing CA IX, reversing acidification mediated by this enzyme. The design of fluorescent sulfonamides that preferentially inhibit the activity of CA IX, showing reduced penetration through the plasma membranes and binding to hypoxic cells expressing CA IX, is reported here. These inhibitors represent promising candidates for developing anticancer therapies based on tumor-associated CA isozyme inhibition and offer interesting tools for imaging and further investigation of hypoxic tumors.
• Sulfonamides incorporating boroxazolidone moieties are potent inhibitors of the transmembrane, tumor-associated carbonic anhydrase isoforms IX and XII
  作者：Marouan Rami、Alfonso Maresca、Fatma-Zhora Smaine、Jean-Louis Montero、Andrea Scozzafava、Jean-Yves Winum、Claudiu T. Supuran

  DOI：10.1016/j.bmcl.2011.03.055

  日期：2011.5

  A new series of sulfonamides was synthesized by the reaction of the boroxazolidone complex of L-lysine with isothiocyanates incorporating sulfamoyl moieties and diverse organic scaffolds. The obtained thioureas have been investigated as inhibitors of four physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IX and XII. Inhibition between the low nanomolar to the micromolar range has been observed against them, with several low nanomolar and tumor-CA selective inhibitors detected. These boron-containing compounds might be useful for the management of hypoxic tumors overexpressing hCA IX/XII by means of boron neutron capture therapy, a technique not investigated so far with inhibitors of this enzyme. (C) 2011 Elsevier Ltd. All rights reserved.