2,2-dioxo-2H-2λ⁶-benzo[e][1,2]oxathiin-6-ol | 1383813-20-4

• 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-6-ol
• 英文别名: 6-hydroxybenzo[e][1,2]oxathiine 2,2-dioxide；1,2-benzoxathiin-6-ol 2,2-dioxide；2,2-Dioxo-1,2lambda6-benzoxathiin-6-ol；2,2-dioxo-1,2λ6-benzoxathiin-6-ol
• CAS: 1383813-20-4
• 化学式: C₈H₆O₄S
• 分子量: 198.199
• InChiKey: VAQVBXKIUYUXIY-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-6-ol 在 铜 、 四甲基氯化铵 、 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 甲苯 、 叔丁醇 为溶剂， 反应 5.0h， 生成 1-(4-(4-(((2,2-dioxidobenzo[e][1,2]oxathiin-6-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  Azidothymidine “Clicked” into 1,2,3-Triazoles: First Report on Carbonic Anhydrase–Telomerase Dual-Hybrid Inhibitors

  摘要：

  Cancer cells rely on the enzyme telomerase (EC 2.7.7.49) to promote cellular immortality. Telomerase inhibitors (i.e., azidothymidine) can represent promising antitumor agents, although showing high toxicity when administered alone. Better outcomes were observed within a multipharmacological approach instead. In this context, we exploited the validated antitumor targets carbonic anhydrases (CAs; EC 4.2.1.1) IX and XII to attain the first proof of concept on CA-telomerase dual-hybrid inhibitors. Compounds 1b, 7h, 8b, and 11b showed good in vitro inhibition potency against the CAs IX and XII, with K-I values in the low nanomolar range, and strong antitelomerase activity in PC-3 and HT-29 cells (IC(50 )values ranging from 5.2 to 9.1 mu M). High-resolution X-ray crystallography on selected derivatives in the adduct with hCA II as a model study allowed to determine their binding modes and thus to set the structural determinants necessary for further development of compounds selectively targeting the tumoral cells.

  DOI：

  10.1021/acs.jmedchem.0c00636
• 作为产物：
  描述：

  2,5-二羟基苯甲醛 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 29.67h， 生成 2,2-dioxo-2H-2λ⁶-benzo[e][1,2]oxathiin-6-ol
  参考文献：
  名称：

  香豆素生物等排体的简便合成—1,2-苯并草嘌呤2,2-二氧化物

  摘要：

  提出了一种简单且可重复的合成香豆素生物等位基因-1,2-苯并草嘌呤2,2-二氧化物的方法。所开发的方法基于在强有机碱存在下甲基水杨醛醛衍生物的分子内羟醛环化反应，其中使用1,8-二氮杂双环[5.4.0] undec-7-ene（DBU）可获得最佳结果。已经表明，取决于芳环中取代基的性质，与标题化合物以不同比例形成了中间的醛醇加合物（3,4-二氢-1，2-苯并氧杂蒽-4-醇2，2-二氧化物）。 。用POCl 3脱水中间醇醛导致完全转化为1，2-苯并硫代嘧啶2，2-二氧化物衍生物。单晶X射线结构明确证明了1,2-二氧苯并ath啶2,2-二氧化物的支架。

  DOI：

  10.1016/j.tet.2012.04.080

文献信息

• 6-Substituted 1,2-benzoxathiine-2,2-dioxides are isoform-selective inhibitors of human carbonic anhydrases IX, XII and VA
  作者：Muhammet Tanc、Fabrizio Carta、Andrea Scozzafava、Claudiu T. Supuran

  DOI：10.1039/c4ob02155j

  日期：——

  A series of 6-substituted 2-benzoxathiine-2,2-dioxides were synthesized starting from 2,5-dihydroxybenzaldehyde, and then screened in vitro for their inhibition properties against five human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms.

  一系列6-取代的2-苯并硫杂喙-2,2-二氧化物从2,5-二羟基苯甲醛合成，并在体外对其抑制五种人类碳酸酐酶（hCA，EC 4.2.1.1）同工酶的性能进行筛选。
• Azidothymidine “Clicked” into 1,2,3-Triazoles: First Report on Carbonic Anhydrase–Telomerase Dual-Hybrid Inhibitors
  作者：Emanuela Berrino、Andrea Angeli、Dmitry D. Zhdanov、Anna P. Kiryukhina、Andrea Milaneschi、Alessandro De Luca、Murat Bozdag、Simone Carradori、Silvia Selleri、Gianluca Bartolucci、Thomas S. Peat、Marta Ferraroni、Claudiu T. Supuran、Fabrizio Carta

  DOI：10.1021/acs.jmedchem.0c00636

  日期：2020.7.9

  Cancer cells rely on the enzyme telomerase (EC 2.7.7.49) to promote cellular immortality. Telomerase inhibitors (i.e., azidothymidine) can represent promising antitumor agents, although showing high toxicity when administered alone. Better outcomes were observed within a multipharmacological approach instead. In this context, we exploited the validated antitumor targets carbonic anhydrases (CAs; EC 4.2.1.1) IX and XII to attain the first proof of concept on CA-telomerase dual-hybrid inhibitors. Compounds 1b, 7h, 8b, and 11b showed good in vitro inhibition potency against the CAs IX and XII, with K-I values in the low nanomolar range, and strong antitelomerase activity in PC-3 and HT-29 cells (IC(50 )values ranging from 5.2 to 9.1 mu M). High-resolution X-ray crystallography on selected derivatives in the adduct with hCA II as a model study allowed to determine their binding modes and thus to set the structural determinants necessary for further development of compounds selectively targeting the tumoral cells.
• Facile synthesis of coumarin bioisosteres—1,2-benzoxathiine 2,2-dioxides
  作者：Aiga Grandane、Sergey Belyakov、Peteris Trapencieris、Raivis Zalubovskis

  DOI：10.1016/j.tet.2012.04.080

  日期：2012.7

  A simple and reproducible procedure for the synthesis of bioisosteres of coumarin—1,2-benzoxathiine 2,2-dioxide is presented. The developed method is based on the intramolecular aldol cyclization of derivatives of mesylsalicyl aldehydes in the presence of strong organic bases, where best results were obtained with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). It has been shown that depending on the nature

  提出了一种简单且可重复的合成香豆素生物等位基因-1,2-苯并草嘌呤2,2-二氧化物的方法。所开发的方法基于在强有机碱存在下甲基水杨醛醛衍生物的分子内羟醛环化反应，其中使用1,8-二氮杂双环[5.4.0] undec-7-ene（DBU）可获得最佳结果。已经表明，取决于芳环中取代基的性质，与标题化合物以不同比例形成了中间的醛醇加合物（3,4-二氢-1，2-苯并氧杂蒽-4-醇2，2-二氧化物）。 。用POCl 3脱水中间醇醛导致完全转化为1，2-苯并硫代嘧啶2，2-二氧化物衍生物。单晶X射线结构明确证明了1,2-二氧苯并ath啶2,2-二氧化物的支架。