2-formyl-4-nitrophenyl methanesulfonate | 67326-25-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-formyl-4-nitrophenyl methanesulfonate
• 英文别名: (2-formyl-4-nitrophenyl) methanesulfonate
• CAS: 67326-25-4
• 化学式: C₈H₇NO₆S
• mdl: MFCD00275483
• 分子量: 245.213
• InChiKey: FKPRPRICPJNTKV-UHFFFAOYSA-N

物化性质

• 熔点：
  98 °C

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  115
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-formyl-4-nitrophenyl methanesulfonate 在 吡啶 、 铁粉 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 12.0h， 生成 N-(2,2-dioxido-1,2-benzoxathiin-6-yl)-4-methylbenzamide
  参考文献：
  名称：

  6-Substituted Sulfocoumarins Are Selective Carbonic Anhdydrase IX and XII Inhibitors with Significant Cytotoxicity against Colorectal Cancer Cells

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.5b00523
• 作为产物：
  描述：

  甲基磺酰氯 、 5-硝基水杨醛 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 22.17h， 以99%的产率得到2-formyl-4-nitrophenyl methanesulfonate
  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

• Ureidosulfocoumarin Derivatives As Selective and Potent Carbonic Anhydrase IX and XII Inhibitors
  作者：Priti Singh、Dilep Kumar Sigalapalli、Nerella Sridhar Goud、Baijayantimala Swain、Santosh Kumar Sahoo、Andrea Angeli、Afzal B. Shaik、Venkata Madhavi Yaddanapudi、Claudiu T. Supuran、Mohammed Arifuddin

  DOI：10.1002/cmdc.202100725

  日期：2022.3.4

  the focus of increased attention. Herein we report 30 non-sulfonamide sulfocoumarin derivatives. All compounds showed selectivity for the tumor-associated isoenzymes hCA IX and XII over the cytosolic isoenzymes hCA I and II. These results provide a new perspective for the development of non-sulfonamide derivatives as selective CA inhibitors.

  鉴于磺胺类碳酸酐酶 (CA) 抑制剂的各种缺点，非磺胺类 CA 抑制剂是越来越受关注的焦点。在这里，我们报告了 30 种非磺酰胺磺基香豆素衍生物。所有化合物都显示出对肿瘤相关同工酶 hCA IX 和 XII 的选择性高于胞质同工酶 hCA I 和 II。这些结果为开发非磺胺类衍生物作为选择性CA抑制剂提供了新的视角。
• Glyoxalase 1 and 2 Enzyme Inhibitory Activity of 6-Sulfamoylsaccharin and Sulfocoumarin Derivates
  作者：Marina Makrecka、Raivis Zalubovskis、Edijs Vavers、Jekaterina Ivanova、Aiga Grandane、Maija Dambrova

  DOI：10.2174/1570180811310050007

  日期：2013.4.1

  glyoxalase enzymes represent a cellular defence system against the accumulation of cytotoxic α- oxoaldehydes leading to apoptosis. The potential of glyoxalase inhibitors to act as novel anti-cancer agents for drugresistant tumours that over-express glyoxalase is currently under investigation. In the present study, a series of 6- sulfamoylsaccharin and 1,2-benzoxathiine 2,2-dioxide (sulfocoumarin - coumarin

  乙二醛酶代表针对细胞毒性α-氧醛积累导致细胞凋亡的细胞防御系统。乙二醛酶抑制剂作为过表达乙二醛酶的耐药性肿瘤的新型抗癌药的潜力目前正在研究中。在本研究中，已测试了一系列6-氨基磺酰基糖精和1,2-二氧杂苯并噻吩2,2-二氧化物（磺香豆素-香豆素的生物甾醇）衍生物以及反式肉桂酸（香豆素水解产物的模拟物）的抑制作用。乙醛酸酶1和2的合成。首次证明6-氨磺酰基糖精具有乙醛酸酶1的抑制活性（IC 50等于90±15μM）。两种化合物5b和9c略微抑制了乙二醛酶2的活性。此外，已证明反式肉桂酸可抑制乙二醛酶1的活性（IC 50等于84±4μM）。这些数据表明6-氨磺酰基糖精结构的修饰和香豆素水解产物可用于开发潜在的乙二醛酶1抑制剂。
• New coumarin/sulfocoumarin linked phenylacrylamides as selective transmembrane carbonic anhydrase inhibitors: Synthesis and in-vitro biological evaluation
  作者：Baijayantimala Swain、Andrea Angeli、Priti Singh、Claudiu T. Supuran、Mohammed Arifuddin

  DOI：10.1016/j.bmc.2020.115586

  日期：2020.8

  Two novel series of phenylacrylamide linked coumarins and sulfocoumarins (6a-p, 8a-i, and 14a-g) were synthesized and evaluated against four physiologically relevant human carbonic anhydrases (hCAs, EC 4.2.1.1), isoforms hCA I, hCA II, hCA IX and hCA XII for their inhibitory action. All new compounds when screened for carbonic anhydrase inhibitory activity have shown selective inhibition towards the

  两种新型系列苯基丙烯酰胺连接的香豆素和sulfocoumarins（的图6a-P ，8A- i和14A-G ）的合成和对四名生理学相关的人类碳酸酐酶（HCAS，EC 4.2.1.1）来评价，同种型HCA I，II HCA， hCA IX和hCA XII具有抑制作用。当筛选碳酸酐酶抑制活性时，所有新化合物均显示出相对于CA I和II对与肿瘤相关的同工型hCA IX和XII的选择性抑制，抑制常数在亚微摩尔至低纳摩尔范围内。化合物6b和14g对hCA IX表现出显着的抑制作用，纳摩尔浓度低，而6k对hCA XII有效。化合物基于新的作用机理，图6b，14g和6k可以被认为是用于癌症治疗的未来发展的先导分子。
• 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。
• 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.