6-iodo-1,2-benzoxathiine 2,2-dioxide | 1571901-96-6

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 6-iodo-1,2-benzoxathiine 2,2-dioxide
• 英文别名: 6-iodo-sulfocoumarin；6-Iodo-1,2lambda6-benzoxathiine 2,2-dioxide；6-iodo-1,2λ6-benzoxathiine 2,2-dioxide
• CAS: 1571901-96-6
• 化学式: C₈H₅IO₃S
• 分子量: 308.096
• InChiKey: IOQLDYALFMNXKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 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：
  51.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(naphthalene-1-yl)-1H-1,2,3,4-tetrazole 、 6-iodo-1,2-benzoxathiine 2,2-dioxide 在 copper(l) iodide 、 三(2-呋喃基)膦 、 palladium diacetate 、 caesium carbonate 作用下， 以 甲苯 为溶剂， 反应 20.0h， 以43%的产率得到5-(2,2-dioxido-1,2-benzoxathiin-6-yl)-1-(naphthalen-1-yl)-1H-tetrazole
  参考文献：
  名称：

  Synthesis of 6-tetrazolyl-substituted sulfocoumarins acting as highly potent and selective inhibitors of the tumor-associated carbonic anhydrase isoforms IX and XII

  摘要：

  A series of 6-substituted sulfocoumarins incorporating substituted-1,2,3,4-tetrazol-5-yl moieties were synthesized by reaction of 6-iodo-sulfocoumarin and the corresponding tetrazole via the CH activation reaction. The new sulfocoumarins incorporating alkyl and substituted aryl moieties at the 1-position of the tetrazole, 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 tetrazole-substituted sulfocoumarins did not inhibit the ubiquitous, off-target cytosolic isoforms (K(I)s > 10 mu M) but showed effective inhibition against the two transmembrane CAs, with KIs ranging from 6.5 to 68.6 nM against hCA IX, and between 4.3 and 59.8 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.bmc.2014.01.043
• 作为产物：
  描述：

  2-formyl-4-iodophenyl methanesulfonate 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 吡啶 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以71%的产率得到6-iodo-1,2-benzoxathiine 2,2-dioxide
  参考文献：
  名称：

  6-芳基取代磺基香豆素的合成及其碳酸酐酶抑制作用的研究

  摘要：

  通过使6-碘-磺基香豆素与芳基硼酸在Suzuki交叉偶联条件下反应，获得了一系列6-芳基取代的1,2-苯并x啶2,2-二氧化物。在药物化学应用，胞质hCA I和II以及药物化学应用方面，研究了在杂环6位上掺入各种取代苯基部分的新磺基香豆素类化合物对四种人（h）碳酸酐酶（CA，EC 4.2.1.1）同工型的抑制作用。跨膜，肿瘤相关的hCA IX和XII。芳基取代的磺香豆素没有抑制普遍存在的，脱靶的胞质亚型hCA I和II（K I s> 10μM），但是显示出对两个跨膜CA的有效抑制，其中K I针对hCA IX的范围为9.0至95.3 nM，针对hCA XII的范围为3.5至14.2 nM。由于hCA IX和XII是经过验证的抗肿瘤靶标，因此此类磺基香豆素，同工型选择性抑制剂可用于鉴定合适的候选药物，以用于此类药物的进一步临床试验。

  DOI：

  10.1016/j.bmc.2015.02.023

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。
• 6-Substituted Sulfocoumarins Are Selective Carbonic Anhdydrase IX and XII Inhibitors with Significant Cytotoxicity against Colorectal Cancer Cells
  作者：Aiga Grandane、Muhammet Tanc、Lorenzo Di Cesare Mannelli、Fabrizio Carta、Carla Ghelardini、Raivis Žalubovskis、Claudiu T. Supuran

  DOI：10.1021/acs.jmedchem.5b00523

  日期：2015.5.14

  6-Substituted sulfocoumarins bearing the carboxamido, trimethylammonium as well as the cyano and methoxy moieties with interesting inhibitory activity/selectivity against the tumor associated carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA IX and XII are reported. Moieties leading to the best inhibition were tert-butylcarboxamido, phenylcarboxamido, and 4-pyridylcarboxamido, with K-I values of 2.1-8.1 nM. No inhibition of the off-target hCA II and I was observed. A number of these compounds were evaluated against HT-29 colon cancer cell lines ex vivo. Compounds 9c and 9e revealed effective cytotoxic effects after 72 h of incubation in both normoxic and hypoxic conditions, unlike sulfonamide CA inhibitors that show such effects only in hypoxia. These results may be of particular importance for the choice of future drug candidates targeting hypoxic tumors and metastases, considering the fact that a sulfonamide CA IX inhibitor (SLC-0111) is presently in phase I clinical trials.