2,2-dioxo-2H-2λ⁶-benzo[e][1,2]oxathiin-7-ol | 1447351-57-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2,2-dioxo-2H-2λ⁶-benzo[e][1,2]oxathiin-7-ol
• 英文别名: 7-hydroxysulfocoumarin；7-hydroxybenzo[e][1,2]oxathiine 2,2-dioxide；2,2-Dioxo-1,2lambda6-benzoxathiin-7-ol；2,2-dioxo-1,2λ6-benzoxathiin-7-ol
• CAS: 1447351-57-6
• 化学式: C₈H₆O₄S
• 分子量: 198.199
• InChiKey: CAFMYROGFUAKMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  72
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,2-dioxo-2H-2λ⁶-benzo[e][1,2]oxathiin-7-ol 在 铜 、 四甲基氯化铵 、 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 5.5h， 生成 1-(3-chlorophenyl)-4-(2,2-dioxo-2H-2λ⁶-benzo-[e][1,2]-oxathiin-7-yloxymethyl)-1H-[1,2,3]-triazole
  参考文献：
  名称：

  7-Aryl-triazolyl-substituted sulfocoumarins are potent, selective inhibitors of the tumor-associated carbonic anhydrase IX and XII

  摘要：

  Sulfocoumarins behave as interesting inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Here, we report a new series of 7-substituted derivatives which were obtained by the click chemistry approach from 7-propargyloxy-sulfocoumarin and aryl azides incorporating halogens, hydroxy, methoxy and carboxyl moieties in their molecules. The new compounds were screened for the inhibition on four physiologically relevant human CA (hCA) isoforms, the cytosolic hCA I and II and the transmembrane tumor-associated hCA IX and XII. The new compounds did not inhibit the cytosolic isoforms but were low nanomolar inhibitors of the tumor-associated ones hCA IX and XII.

  DOI：

  10.3109/14756366.2015.1115401
• 作为产物：
  描述：

  4-苯甲氧基-2-羟基苯甲醛 在 palladium 10% on activated carbon 、 氢气 、 四乙基氢氧化铵 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 20.0 ℃ 、413.7 kPa 条件下， 生成 2,2-dioxo-2H-2λ⁶-benzo[e][1,2]oxathiin-7-ol
  参考文献：
  名称：

  7-Substituted-sulfocoumarins are isoform-selective, potent carbonic anhydrase II inhibitors

  摘要：

  A series of 7-substituted sulfocoumarins and 3,4-dihydrosulfocoumarins was obtained by cyclization of the methanesulfonate of 2,4-dihydroxy- or 2-hydroxy-4-methoxybenzaldehyde, followed by derivatization reactions. The new compounds incorporate a range of substituents in position 7 of the heterocyclic ring (hydroxyl, methoxy, carboxylic and alkylsulfonate ester). The compounds were tested for the inhibition of the zinc enzyme human (h) carbonic anhydrase (hCA, EC 4.2.1.1). Unlike the 6-substituted sulfocoumarins which were potent hCA IX and XII inhibitors and ineffective hCA I and II inhibitors, compounds from this series showed low nanomolar hCA II inhibitory properties, and inhibited the mitochondrial isoform hCA VA with K(I)s in the range of 91-9960 nM, but were ineffective as hCA I, IX and XII inhibitors. The structure activity relationship for this class of inhibitors was rather clear, with the nature of the 7-substituent strongly influencing hCA VA inhibition, whereas the nature of these groups were less relevant for hCA II inhibition (all reported compounds were highly effective hCA II inhibitors, with K(I)s in the range of 1.5-8.4 nM). Since both hCA II and hCA VA are important drug targets (hCA II for antiglaucoma agents; hCA VA for antiobesity drugs), these isoform-selective inhibitors reported here may be considered of interest for various biomedical applications. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.032

文献信息

• Continued Structural Exploration of Sulfocoumarin as Selective Inhibitor of Tumor-Associated Human Carbonic Anhydrases IX and XII
  作者：Simone Giovannuzzi、Clemente Capasso、Alessio Nocentini、Claudiu T. Supuran

  DOI：10.3390/molecules27134076

  日期：——

  A series of new 3- and 7-substituted sulfocoumarins was obtained by several cyclization reactions and subsequent derivatization for screening as prodrug inhibitors of the human (h) cancer-associated carbonic anhydrases (CAs) IX and XII. All products were ineffective inhibitors against the off-target hCA I and II, whilst hCAs IX and XII were inhibited with inhibition constants (KIs) spanning from low nanomolar to the high micromolar range, according to the sulfocoumarin derivatization pattern. In particular, sulfocoumarin 15 turned out to be the most potent and selective inhibitor herein reported (hCA I and II: KI > 100 µM; hCA IX: KI = 22.9 nM; hCA XII: KI = 19.2 nM). Considering that hCA IX and XII validated anti-tumor targets, such prodrug, isoform-selective inhibitors as the sulfocoumarins reported here may be useful for identifying suitable drug candidates for clinical trials.

  一系列新的3-和7-取代磺酰香豆素通过多个环化反应和随后的衍生化反应获得，用于筛选作为人类（h）癌症相关的碳酸酐酶（CAs）IX和XII的前药抑制剂。所有产物都对非靶向的hCA I和II无效，而hCAs IX和XII则被抑制，抑制常数（KIs）根据磺酰香豆素的衍生化模式在低纳摩尔到高微摩尔范围内变化。特别是，磺酰香豆素15被证明是此处报道的最有效和选择性的抑制剂（hCA I和II：KI> 100µM；hCA IX：KI = 22.9 nM；hCA XII：KI = 19.2 nM）。考虑到hCA IX和XII是经过验证的抗肿瘤靶点，因此此处报道的磺酰香豆素等前药、同工酶选择性抑制剂可能有助于鉴定适合的药物候选物进行临床试验。
• 7-Aryl-triazolyl-substituted sulfocoumarins are potent, selective inhibitors of the tumor-associated carbonic anhydrase IX and XII
  作者：Alessio Nocentini、Mariangela Ceruso、Fabrizio Carta、Claudiu T. Supuran

  DOI：10.3109/14756366.2015.1115401

  日期：2016.11.1

  Sulfocoumarins behave as interesting inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Here, we report a new series of 7-substituted derivatives which were obtained by the click chemistry approach from 7-propargyloxy-sulfocoumarin and aryl azides incorporating halogens, hydroxy, methoxy and carboxyl moieties in their molecules. The new compounds were screened for the inhibition on four physiologically relevant human CA (hCA) isoforms, the cytosolic hCA I and II and the transmembrane tumor-associated hCA IX and XII. The new compounds did not inhibit the cytosolic isoforms but were low nanomolar inhibitors of the tumor-associated ones hCA IX and XII.
• 7-Substituted-sulfocoumarins are isoform-selective, potent carbonic anhydrase II inhibitors
  作者：Muhammet Tanc、Fabrizio Carta、Murat Bozdag、Andrea Scozzafava、Claudiu T. Supuran

  DOI：10.1016/j.bmc.2013.05.032

  日期：2013.8

  A series of 7-substituted sulfocoumarins and 3,4-dihydrosulfocoumarins was obtained by cyclization of the methanesulfonate of 2,4-dihydroxy- or 2-hydroxy-4-methoxybenzaldehyde, followed by derivatization reactions. The new compounds incorporate a range of substituents in position 7 of the heterocyclic ring (hydroxyl, methoxy, carboxylic and alkylsulfonate ester). The compounds were tested for the inhibition of the zinc enzyme human (h) carbonic anhydrase (hCA, EC 4.2.1.1). Unlike the 6-substituted sulfocoumarins which were potent hCA IX and XII inhibitors and ineffective hCA I and II inhibitors, compounds from this series showed low nanomolar hCA II inhibitory properties, and inhibited the mitochondrial isoform hCA VA with K(I)s in the range of 91-9960 nM, but were ineffective as hCA I, IX and XII inhibitors. The structure activity relationship for this class of inhibitors was rather clear, with the nature of the 7-substituent strongly influencing hCA VA inhibition, whereas the nature of these groups were less relevant for hCA II inhibition (all reported compounds were highly effective hCA II inhibitors, with K(I)s in the range of 1.5-8.4 nM). Since both hCA II and hCA VA are important drug targets (hCA II for antiglaucoma agents; hCA VA for antiobesity drugs), these isoform-selective inhibitors reported here may be considered of interest for various biomedical applications. (C) 2013 Elsevier Ltd. All rights reserved.