5-(4-Isothiocyanato-benzenesulfonylamino)-[1,3,4]thiadiazole-2-sulfonic acid amide | 813463-09-1

• 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: 5-(4-Isothiocyanato-benzenesulfonylamino)-[1,3,4]thiadiazole-2-sulfonic acid amide
• 英文别名: 5-[(4-isothiocyanatophenyl)sulfonylamino]-1,3,4-thiadiazole-2-sulfonamide
• CAS: 813463-09-1
• 化学式: C₉H₇N₅O₄S₄
• 分子量: 377.45
• InChiKey: BHGXZDRFYWOZFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  222
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  1,4-双(3-氨基丙基)哌嗪 、 5-(4-Isothiocyanato-benzenesulfonylamino)-[1,3,4]thiadiazole-2-sulfonic acid amide 生成 Aminobenzolamide derivative
  参考文献：
  名称：

  碳酸酐酶抑制剂：与衍生自4-isothiocyanato-benzolamide的磺酰胺合成和抑制胞质/肿瘤相关的碳酸酐酶同工酶I，II和IX。

  摘要：

  由氨基苯甲酰胺和硫光气制备了一系列结合有4-硫脲基-苯甲酰胺基团的磺酰胺，然后使硫氰酸根中间体与脂族/芳族胺或肼反应。已经研究了这些新衍生物作为锌酶碳酸酐酶（CA，EC 4.2.1.1）的抑制剂，更确切地说是胞质同工酶hCA I和II以及与肿瘤相关的同工酶hCA IX（都是人类起源的）的抑制剂。 ）。新化合物对所有三种同工酶均显示出优异的抑制特性，其抑制常数分别为针对hCA I的0.6-62 nM，针对hCA II的0.5-1.7 nM和针对hCA IX的3.2-23 nM。这些衍生物是开发针对缺氧肿瘤的新疗法的有趣候选物。

  DOI：

  10.1016/j.bmcl.2004.09.062
• 作为产物：
  描述：

  硫光气 、 5-[(4-氨基苯基)磺酰基氨基]-1,3,4-噻二唑-2-磺酰胺 在 盐酸 作用下， 生成 5-(4-Isothiocyanato-benzenesulfonylamino)-[1,3,4]thiadiazole-2-sulfonic acid amide
  参考文献：
  名称：

  碳酸酐酶抑制剂：与衍生自4-isothiocyanato-benzolamide的磺酰胺合成和抑制胞质/肿瘤相关的碳酸酐酶同工酶I，II和IX。

  摘要：

  由氨基苯甲酰胺和硫光气制备了一系列结合有4-硫脲基-苯甲酰胺基团的磺酰胺，然后使硫氰酸根中间体与脂族/芳族胺或肼反应。已经研究了这些新衍生物作为锌酶碳酸酐酶（CA，EC 4.2.1.1）的抑制剂，更确切地说是胞质同工酶hCA I和II以及与肿瘤相关的同工酶hCA IX（都是人类起源的）的抑制剂。 ）。新化合物对所有三种同工酶均显示出优异的抑制特性，其抑制常数分别为针对hCA I的0.6-62 nM，针对hCA II的0.5-1.7 nM和针对hCA IX的3.2-23 nM。这些衍生物是开发针对缺氧肿瘤的新疗法的有趣候选物。

  DOI：

  10.1016/j.bmcl.2004.09.062

文献信息

• Carbonic anhydrase inhibitors. Synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with boron-containing sulfonamides, sulfamides, and sulfamates: Toward agents for boron neutron capture therapy of hypoxic tumors
  作者：Jean-Yves Winum、Alessandro Cecchi、Jean-Louis Montero、Alessio Innocenti、Andrea Scozzafava、Claudiu T. Supuran

  DOI：10.1016/j.bmcl.2005.04.058

  日期：2005.7

  against hCA IX in the range of 7.3-89nM, respectively. As hypoxic tumors highly overexpress CA IX, the design of boron-containing inhibitors with high affinity for the tumor-associated CA isozymes may lead to important advances in boron neutron capture therapy (BNCT) applications targeting such tumors, which are non-responsive to both classical chemo- and radiotherapy.

  据报道，含硼的碳酸酐酶（CA，EC 4.2.1.1）抑制剂库包括磺酰胺，磺酰胺和氨基磺酸盐。通过4-羧基-/氨基-/羟基-苯基硼酸频哪醇酯与氨基/异硫氰酸根基取代的芳族/杂芳族磺酰胺的衍生化反应或与氨磺酰氯的氨磺酰化反应，可以合成新化合物。已经测定了这些新衍生物对三种生理相关的CA同工酶（胞质CA I和II，以及跨膜的肿瘤相关同工酶IX）的抑制作用。在磺酰胺，氨基磺酸盐和磺酰胺中均检测到有效的抑制剂。新化合物针对人同工酶hCA I的抑制常数范围为34-94nM，针对hCA II的抑制常数范围为3.1-48nM，针对hCA IX的抑制常数范围为7。分别为3-89nM。由于缺氧性肿瘤高度表达CA IX，因此设计与肿瘤相关的CA同工酶具有高亲和力的含硼抑制剂可能会导致针对此类肿瘤的硼中子俘获疗法（BNCT）应用的重要进展，而这对两种肿瘤均无反应经典的化学和放射疗法。
• 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 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.
• Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with sulfonamides derived from 4-isothiocyanato-benzolamide
  作者：Alessandro Cecchi、Jean-Yves Winum、Alessio Innocenti、Daniela Vullo、Jean-Louis Montero、Andrea Scozzafava、Claudiu T. Supuran

  DOI：10.1016/j.bmcl.2004.09.062

  日期：2004.12

  series of sulfonamides incorporating 4-thioureido-benzolamide moieties have been prepared from aminobenzolamide and thiophosgene followed by the reaction of the thiocyanato intermediate with aliphatic/aromatic amines or hydrazines. The new derivatives have been investigated as inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), and more precisely of the cytosolic isozymes hCA I and II, as

  由氨基苯甲酰胺和硫光气制备了一系列结合有4-硫脲基-苯甲酰胺基团的磺酰胺，然后使硫氰酸根中间体与脂族/芳族胺或肼反应。已经研究了这些新衍生物作为锌酶碳酸酐酶（CA，EC 4.2.1.1）的抑制剂，更确切地说是胞质同工酶hCA I和II以及与肿瘤相关的同工酶hCA IX（都是人类起源的）的抑制剂。 ）。新化合物对所有三种同工酶均显示出优异的抑制特性，其抑制常数分别为针对hCA I的0.6-62 nM，针对hCA II的0.5-1.7 nM和针对hCA IX的3.2-23 nM。这些衍生物是开发针对缺氧肿瘤的新疗法的有趣候选物。