1-(3-chloro-4-fluorophenyl)-5-(2,2-dioxido-1,2-benzoxathiin-6-yl)-1H-tetrazole | 1571902-04-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(3-chloro-4-fluorophenyl)-5-(2,2-dioxido-1,2-benzoxathiin-6-yl)-1H-tetrazole
• 英文别名: 1-(2,2-dioxido-1,2-benzoxathiin-6-yl)-5-(4-fluorophenyl)-1H-1,2,3-triazole；6-[1-(3-Chloro-4-fluorophenyl)tetrazol-5-yl]-1,2lambda6-benzoxathiine 2,2-dioxide；6-[1-(3-chloro-4-fluorophenyl)tetrazol-5-yl]-1,2λ6-benzoxathiine 2,2-dioxide
• CAS: 1571902-04-9
• 化学式: C₁₅H₈ClFN₄O₃S
• 分子量: 378.771
• InChiKey: RGPOASFPAYLZKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  95.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-formyl-4-iodophenyl methanesulfonate 在 copper(l) iodide 、 三(2-呋喃基)膦 、 palladium diacetate 、 caesium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 25.0h， 生成 1-(3-chloro-4-fluorophenyl)-5-(2,2-dioxido-1,2-benzoxathiin-6-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

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。