7-methoxybenzo[e][1,2]oxathiine 2,2-dioxide | 1447351-66-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 7-methoxybenzo[e][1,2]oxathiine 2,2-dioxide
• 英文别名: 7-Methoxy-1,2lambda6-benzoxathiine 2,2-dioxide；7-methoxy-1,2λ6-benzoxathiine 2,2-dioxide
• CAS: 1447351-66-7
• 化学式: C₉H₈O₄S
• 分子量: 212.226
• InChiKey: FJVKKCZTNRYTJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  61
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-methoxybenzo[e][1,2]oxathiine 2,2-dioxide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以72%的产率得到2,2-dioxo-2H-2λ⁶-benzo[e][1,2]oxathiin-7-ol
  参考文献：
  名称：

  Continued Structural Exploration of Sulfocoumarin as Selective Inhibitor of Tumor-Associated Human Carbonic Anhydrases IX and XII

  摘要：

  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。

  DOI：

  10.3390/molecules27134076
• 作为产物：
  描述：

  methanesulfonic acid 2-formyl-5-methoxyphenyl ester 在 甲基磺酰氯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三氯氧磷 作用下， 以 吡啶 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 7-methoxybenzo[e][1,2]oxathiine 2,2-dioxide
  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

• A Tandem Sulfonylation and Knoevenagel Condensation for the Preparation of Sulfocoumarin-3-carboxylates
  作者：Ziyang Dong、Yang Chen、Zhiheng Yang、Zhanhui Yang、Jiaxi Xu

  DOI：10.1055/s-0037-1611703

  日期：2019.4

  respectively. A gram-scale synthesis and further derivatizations are also reported. The ester group is easily removed via ­Happer’s decarboxylation. Sulfocoumarins are key structural motifs in several bioactive molecules. Herein, we describe a simple, one-pot procedure for the synthesis of structurally diverse sulfonocoumarin-3-carboxylates by heating 2-hydroxyaryl aldehydes with an active sulfonyl chloride

  ‡这些作者对这项工作做出了同等的贡献。 抽象的 磺香豆素是几种生物活性分子中的关键结构基序。在这里，我们描述了一种简单的一锅法，用于通过在吡啶存在下，将2-羟基芳基醛与活性磺酰氯一起加热，来合成结构多样的磺香豆素-3-羧酸酯。该方法可耐受许多官能团，包括烷氧基，烷基，卤素，硝基，甚至亲核酚羟基。另外，2-羟基芳基酮与2-甲基氨基芳基醛的反应分别得到4-取代的磺基香豆素和1-氮杂-2-磺基香豆素。还报道了克级合成和进一步衍生化。酯基很容易通过Happer的脱羧作用除去。 磺香豆素是几种生物活性分子中的关键结构基序。在这里，我们描述了一种简单的一锅法，用于通过在吡啶存在下，将2-羟基芳基醛与活性磺酰氯一起加热，来合成结构多样的磺香豆素-3-羧酸酯。该方法可耐受许多官能团，包括烷氧基，烷基，卤素，硝基，甚至亲核酚羟基。另外，2-羟基芳基酮与2-甲基氨基芳基醛的反应分别得到4-取代的磺基香豆素和1
• 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.
• 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。