6-azido-1,2-benzoxathiine-2,2-dioxide | 1416915-86-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧硫杂环己烯
• 英文名称: 6-azido-1,2-benzoxathiine-2,2-dioxide
• 英文别名: 6-Azido-1,2lambda6-benzoxathiine 2,2-dioxide；6-azido-1,2λ6-benzoxathiine 2,2-dioxide
• CAS: 1416915-86-0
• 化学式: C₈H₅N₃O₃S
• 分子量: 223.212
• InChiKey: ATDIIKIFBWOPQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-azido-1,2-benzoxathiine-2,2-dioxide 、 2-甲基-3-丁炔-2-醇 在 copper(l) iodide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 以72%的产率得到2-[1-(2,2-dioxido-1,2-benzoxathiin-6-yl)-1H-1,2,3-triazol-4-yl]propan-2-ol
  参考文献：
  名称：

  6-Triazolyl-substituted sulfocoumarins are potent, selective inhibitors of the tumor-associated carbonic anhydrases IX and XII

  摘要：

  A series of 6-substituted sulfocoumarins incorporating substituted-1,2,3-triazol-4-yl-/5-yl moieties were synthesized by employing click chemistry. The new sulfocoumarins incorporated cycloalkyl, tert-butyl and substituted aryl moieties at the triazole ring, and were investigated for the inhibition of four human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, the cytosolic hCA I and II; and the transmembrane, tumor-associated hCA IX and XII. The triazole-substituted sulfocoumarins did not inhibit the ubiquitous, off-target cytosolic isoforms hCA I and II (K(I)s > 10 mu M) but showed effective inhibition against the two transmembrane CAs, with KIs ranging from 7.2 to 10.5 nM against hCA IX, and between 5.5 and 17.7 nM against hCA XII. As hCA IX and XII are 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. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.076
• 作为产物：
  描述：

  2-formyl-4-nitrophenyl methanesulfonate 在 盐酸 、 sodium azide 、 铁粉 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 sodium nitrite 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 6-azido-1,2-benzoxathiine-2,2-dioxide
  参考文献：
  名称：

  磺胺香豆素，香豆素，4-氨基甲酰基苯基吲哚-3-羧酰胺杂化物：肿瘤相关的碳酸酐酶同工酶IX和XII的合成和选择性抑制。

  摘要：

  针对缺氧肿瘤：合成了一系列新的含磺基香豆素，香豆素和4-氨磺酰基苯基的吲唑-3-羧酰胺杂化物，并研究了其作为人碳酸酐酶（hCA，EC 4.2.1.1）同工型I，II的抑制剂，IX和XII。这些化合物中的大多数显示出对hCA亚型IX和XII的出色效价和选择性，hCA亚型IX和XII最近已被确认为抗肿瘤药物靶标。

  DOI：

  10.1002/cmdc.201700446

文献信息

• Sulfocoumarins as dual inhibitors of human carbonic anhydrase isoforms IX/XII and of human thioredoxin reductase
  作者：Mikhail Krasavin、Raivis Žalubovskis、Aiga Grandāne、Ilona Domračeva、Petr Zhmurov、Claudiu T. Supuran

  DOI：10.1080/14756366.2020.1712596

  日期：2020.1.1

  acting as inhibitors of human carbonic anhydrase (CA, EC 4.2.1.1) cancer-associated isoforms hCA IX and - hCA XII is being able to also inhibit thioredoxin reductase was verified and confirmed. The dual targeting of two cancer cell defence mechanisms, i.e. hypoxia and oxidative stress, may both contribute to the observed antiproliferative profile of these compounds against many cancer cell lines. This

  证实并证实了硫代香豆素可作为人类碳酸酐酶抑制剂（CA，EC 4.2.1.1）与癌症相关的亚型hCA IX和-hCA XII的抑制剂也能抑制硫氧还蛋白还原酶的假说。两种癌细胞防御机制（即缺氧和氧化应激）的双重靶向可能都有助于观察到的这些化合物对多种癌细胞的抗增殖作用。这种前所未有的双重抗癌机制可能会导致设计创新治疗剂的新方法。
• Sulfocoumarins (1,2-Benzoxathiine-2,2-dioxides): A Class of Potent and Isoform-Selective Inhibitors of Tumor-Associated Carbonic Anhydrases
  作者：Kaspars Tars、Daniela Vullo、Andris Kazaks、Janis Leitans、Alons Lends、Aiga Grandane、Raivis Zalubovskis、Andrea Scozzafava、Claudiu T. Supuran

  DOI：10.1021/jm301625s

  日期：2013.1.10

  Coumarins were recently shown to constitute a novel class of mechanism-based carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. We demonstrate that sulfocoumarins (1,2-benzoxathiine 2,2-dioxides) possess a similar mechanism of action, acting as effective CA inhibitors. The sulfocoumarins were hydrolyzed by the esterase CA activity to 2-hydroxyphenyl-vinylsulfonic acids, which thereafter bind to the enzyme

  最近显示香豆素构成一类新的基于机理的碳酸酐酶（CA，EC 4.2.1.1）抑制剂。我们证明了磺基香豆素（1,2-苯并氧杂氨酸2,2-二氧化物）具有相似的作用机理，可作为有效的CA抑制剂。磺基香豆素通过酯酶CA活性水解为2-羟苯基-乙烯基磺酸，然后在很少被其他类型的抑制剂占据的区域中与该酶结合。这些化合物之一与经修饰的CA II酶加成的X射线结构具有从CA IX活性位点获得的两个氨基酸残基，这使我们能够理解其抑制机理。观察到磺酸固定在锌配位的水分子上，与Thr200和Pro201形成良好的相互作用。其他一些磺基香豆素结合了1,2，
• Evaluation of 99mTc-sulfonamide and sulfocoumarin derivatives for imaging carbonic anhydrase IX expression
  作者：Misaki Nakai、Jihne Pan、Kuo-Shyan Lin、John R. Thompson、Alessio Nocentini、Claudiu T. Supuran、Yasuo Nakabayashi、Tim Storr

  DOI：10.1016/j.jinorgbio.2018.04.009

  日期：2018.8

  With the aim to prepare hypoxia tumor imaging agents, technetium(I) and rhenium(I) tricarbonyl complexes with dipyridylamine (L1 = N-[1-(2,2-dioxido-1,2-benzoxathiin-6-yl)-1H-1,2,3-triazol-4-yl]methyl}-N-(2-pyridinylmethyl)-2-pyridinemethanamine; L3 = N-[1-[N-(4-aminosulfonylphenyl)]-1H-1,2,3-triazol-4-yl]methyl}-N-(2-pyridinyl-methyl)-2-pyridinemethanamine), and iminodiacetate (H2L2 = N-[1-(2,2-dioxido-1

  为了制备缺氧肿瘤显像剂，tech和二羰基胺与三羰基complex（L1  =  N -[1-（2,2-dioxido-1,2-benzoxathiin-6-yl）- 1 H -1,2,3-三唑-4-基]甲基} -N-（2-吡啶基甲基）-2-吡啶甲胺; L3  =  N -[1- [ N-（4-氨基磺酰基苯基）]-1 H -1,2,3-三唑-4-基]甲基} -N-（2-吡啶基-甲基）-2-吡啶甲胺和亚氨基二乙酸酯（H 2 L2  =  N -[1-（2,2-dioxido -1,2-苯并氧杂i啶-6-基）-1 H -1,2,3-三唑-4-基]甲基} -N-（羧甲基）-甘氨酸; H2 L4  = 附在磺酰胺上的N -[1- [ N-（4-氨基磺酰基苯基）]-1 H -1,2,3-三唑-4-基]甲基} -N-（羧甲基）-甘氨酸）配体合成了香豆素碳酸酐酶抑制剂。使用1 H / 13 C N
• 6-Triazolyl-substituted sulfocoumarins are potent, selective inhibitors of the tumor-associated carbonic anhydrases IX and XII
  作者：Aiga Grandane、Muhammet Tanc、Raivis Zalubovskis、Claudiu T. Supuran

  DOI：10.1016/j.bmcl.2014.01.076

  日期：2014.3

  A series of 6-substituted sulfocoumarins incorporating substituted-1,2,3-triazol-4-yl-/5-yl moieties were synthesized by employing click chemistry. The new sulfocoumarins incorporated cycloalkyl, tert-butyl and substituted aryl moieties at the triazole ring, and were investigated for the inhibition of four human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, the cytosolic hCA I and II; and the transmembrane, tumor-associated hCA IX and XII. The triazole-substituted sulfocoumarins did not inhibit the ubiquitous, off-target cytosolic isoforms hCA I and II (K(I)s > 10 mu M) but showed effective inhibition against the two transmembrane CAs, with KIs ranging from 7.2 to 10.5 nM against hCA IX, and between 5.5 and 17.7 nM against hCA XII. As hCA IX and XII are 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. (c) 2014 Elsevier Ltd. All rights reserved.
• Sulfocoumarin-, Coumarin-, 4-Sulfamoylphenyl-Bearing Indazole-3-carboxamide Hybrids: Synthesis and Selective Inhibition of Tumor-Associated Carbonic Anhydrase Isozymes IX and XII
  作者：Srinivas Angapelly、P. V. Sri Ramya、Andrea Angeli、Claudiu T. Supuran、Mohammed Arifuddin

  DOI：10.1002/cmdc.201700446

  日期：2017.10.9

  series of sulfocoumarin-, coumarin-, and 4-sulfamoylphenyl-bearing indazole-3-carboxamide hybrids were synthesized and investigated as inhibitors of human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I, II, IX, and XII. Most of these compounds displayed excellent potency and selectivity against hCA isoforms IX and XII, which have been recently validated as antitumor drug targets.

  针对缺氧肿瘤：合成了一系列新的含磺基香豆素，香豆素和4-氨磺酰基苯基的吲唑-3-羧酰胺杂化物，并研究了其作为人碳酸酐酶（hCA，EC 4.2.1.1）同工型I，II的抑制剂，IX和XII。这些化合物中的大多数显示出对hCA亚型IX和XII的出色效价和选择性，hCA亚型IX和XII最近已被确认为抗肿瘤药物靶标。