3-Chloro-4-isothiocyanato-benzenesulfonamide | 860314-26-7

• 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: 3-Chloro-4-isothiocyanato-benzenesulfonamide
• CAS: 860314-26-7
• 化学式: C₇H₅ClN₂O₂S₂
• 分子量: 248.714
• InChiKey: WLAHMRBOYUOETK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.72
• 重原子数：
  14.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  72.52
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  D-(+)-galactosamine hydrochloride 、 3-Chloro-4-isothiocyanato-benzenesulfonamide 在 碳酸氢钠 作用下， 以 乙腈 为溶剂， 反应 3.0h， 生成 1-(2-chloro-4-sulfamoylphenyl)-3-[(3R,4R,5R,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]thiourea
  参考文献：
  名称：

  碳酸酐酶抑制剂：用糖基-硫脲基-磺酰胺，比同工酶I和II选择性抑制细胞外，与肿瘤相关的同工型IX和XII。

  摘要：

  合成了一系列结合了葡萄糖胺，半乳糖胺和甘露糖胺尾巴的糖基硫脲磺酰胺，以及磺胺，卤代磺胺和间甲酰胺头。许多新化合物显示出微摩尔-亚微摩尔的亲和力，可抑制金属酶碳酸酐酶的胞质同工型I和II（CA，EC 4.2.1.1），但与肿瘤相关同工酶CA IX和XII的纳摩尔结合率低。对于最具选择性的此类抑制剂，与胞质同工酶相比，与肿瘤相关的抑制作用的选择性比在107-955的范围内。

  DOI：

  10.1016/j.bmcl.2007.07.019
• 作为产物：
  描述：

  磺胺 在 盐酸 、 N-氯代丁二酰亚胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 3-Chloro-4-isothiocyanato-benzenesulfonamide
  参考文献：
  名称：

  针对多重耐药淋病奈瑟菌的青霉素碳酸酐酶抑制剂的开发

  摘要：

  开发具有新作用机制的抗菌药物对于对抗抗生素耐药性感染的增加至关重要。细菌碳酸酐酶（CA、EC 4.2.1.1）已被证实是针对幽门螺杆菌、淋病奈瑟菌和万古霉素耐药肠球菌等病原体的有前景的抗菌靶点。提出了一种多靶点策略来设计基于青霉素的 CA 抑制剂杂合体，通过针对多种细菌途径来应对耐药性，从而使耐药菌株对临床抗生素重新敏感。磺酰胺衍生物可有效抑制淋病奈瑟菌和大肠杆菌的 CA， K I值在 7.1–617.2 nM 范围内。对淋病奈瑟菌主要青霉素结合蛋白 (PBP) 的计算模拟表明，这些杂合衍生物保留了先导 β-内酰胺的作用机制。一部分衍生物对多重耐药淋病奈瑟菌菌株表现出有效的 PBP 相关抗淋球菌作用，其中几种化合物显着优于先导 β-内酰胺和 CA 抑制剂药物（MIC 值在 0.25 至 0.5 μg/mL 范围内）。

  DOI：

  10.1021/acs.jmedchem.4c00740

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 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.