N-[6-(aminosulfonyl)-1,3-benzothiazol-2-yl]-2-chloroacetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: N-[6-(aminosulfonyl)-1,3-benzothiazol-2-yl]-2-chloroacetamide
• 英文别名: 2-chloro-N-(6-sulfamoyl-1,3-benzothiazol-2-yl)acetamide
• 化学式: C₉H₈ClN₃O₃S₂
• 分子量: 305.766
• InChiKey: TZAOIFWTLNPQKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  139
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[6-(aminosulfonyl)-1,3-benzothiazol-2-yl]-2-chloroacetamide 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 2-(4-cyano-3-(methylthio)-5-(3-phenylthioureido)-1H-pyrazol-1-yl)-N-(6-sulfamoylbenzo[d]thiazol-2-yl)acetamide
  参考文献：
  名称：

  Design and synthesis of benzothiazole-6-sulfonamides acting as highly potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII

  摘要：

  A series of novel 2-aminobenzothiazole derivatives bearing sulfonamide at position 6 was designed, synthesized and investigated as inhibitors of four isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), the cytosolic CA I and II, and the tumor-associated isozymes CA IX and XII. Docking and binding energy studies were carried out to reveal details regarding the favorable interactions between the scaffolds of these new inhibitors and the active sites of the investigated CA isoforms. Most of the novel compounds were acting as highly potent inhibitors of the tumor-associated hCA IX and hCA XII with K(I)s in the nanomolar range. The ubiquitous and dominant rapid cytosolic isozyme hCA II was also inhibited with K(I)s ranging from 3.5 to 45.4 nM. The favorable interactions between some of the new compounds and the active site of different CA isoforms were delineated by using molecular docking which may be useful for designing compounds with high affinity and selectivity for some CAs with biomedical applications. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.019
• 作为产物：
  描述：

  磺胺 在 盐酸 、 溴 、 三乙胺 作用下， 以 四氢呋喃 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 N-[6-(aminosulfonyl)-1,3-benzothiazol-2-yl]-2-chloroacetamide
  参考文献：
  名称：

  苯和苯并噻唑-磺酰胺类似物作为肿瘤相关碳酸酐酶 IX 选择性抑制剂的开发

  摘要：

  为了开发新的潜在抗肿瘤剂，已使用尾部方法开发了两个系列的苯和苯并噻唑磺酰胺衍生物，作为有效的人碳酸酐酶 (hCA, EC 4.2.1.1) 抑制剂。合成的化合物（XS-1至XS-22) 对 hCA 的生理相关异构体、细胞溶质 CA I 和 II、膜结合 CA IV 和肿瘤相关 CA IX 的抑制作用进行了测定。发现这两个系列的化合物对 CA I、II 和 IX 表现出低至中等纳摩尔范围的抑制作用，对 CA IV 表现出弱抑制作用。一些衍生物在纳摩尔范围内对肿瘤相关的 CA IX 异构体表现出选择性抑制。还筛选了这些有效化合物的选择性毒性，以评估它们对人牙龈成纤维细胞 (HGF) 和乳腺癌细胞系 (MCF7) 的体外抗增殖作用。最后，进行了分子对接研究，以解释那些有助于区分选定的人碳酸酐酶同种型的结构要求。

  DOI：

  10.1016/j.ejmech.2022.114793

文献信息

• Design and synthesis of benzothiazole-6-sulfonamides acting as highly potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII
  作者：Diaa A. Ibrahim、Deena S. Lasheen、Maysoun Y. Zaky、Amany W. Ibrahim、Daniela Vullo、Mariangela Ceruso、Claudiu T. Supuran、Dalal A. Abou El Ella

  DOI：10.1016/j.bmc.2015.05.019

  日期：2015.8

  A series of novel 2-aminobenzothiazole derivatives bearing sulfonamide at position 6 was designed, synthesized and investigated as inhibitors of four isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), the cytosolic CA I and II, and the tumor-associated isozymes CA IX and XII. Docking and binding energy studies were carried out to reveal details regarding the favorable interactions between the scaffolds of these new inhibitors and the active sites of the investigated CA isoforms. Most of the novel compounds were acting as highly potent inhibitors of the tumor-associated hCA IX and hCA XII with K(I)s in the nanomolar range. The ubiquitous and dominant rapid cytosolic isozyme hCA II was also inhibited with K(I)s ranging from 3.5 to 45.4 nM. The favorable interactions between some of the new compounds and the active site of different CA isoforms were delineated by using molecular docking which may be useful for designing compounds with high affinity and selectivity for some CAs with biomedical applications. (C) 2015 Elsevier Ltd. All rights reserved.
• Development of benzene and benzothiazole-sulfonamide analogues as selective inhibitors of the tumor-associated carbonic anhydrase IX
  作者：Shoaib Manzoor、Andrea Angeli、Susi Zara、Simone Carradori、Md Ataur Rahman、Md Kausar Raza、Claudiu T. Supuran、Nasimul Hoda

  DOI：10.1016/j.ejmech.2022.114793

  日期：2022.12

  against CA I, II and IX, and weak inhibition against CA IV. Some of the derivatives displayed selective inhibition towards tumor-associated CA IX isoform, within the nanomolar range. These potent compounds were also screened for their selective toxicity to evaluate their in vitro anti-proliferative effects on Human Gingival Fibroblasts (HGFs) and breast adenocarcinoma cell line (MCF7). Lastly, molecular

  为了开发新的潜在抗肿瘤剂，已使用尾部方法开发了两个系列的苯和苯并噻唑磺酰胺衍生物，作为有效的人碳酸酐酶 (hCA, EC 4.2.1.1) 抑制剂。合成的化合物（XS-1至XS-22) 对 hCA 的生理相关异构体、细胞溶质 CA I 和 II、膜结合 CA IV 和肿瘤相关 CA IX 的抑制作用进行了测定。发现这两个系列的化合物对 CA I、II 和 IX 表现出低至中等纳摩尔范围的抑制作用，对 CA IV 表现出弱抑制作用。一些衍生物在纳摩尔范围内对肿瘤相关的 CA IX 异构体表现出选择性抑制。还筛选了这些有效化合物的选择性毒性，以评估它们对人牙龈成纤维细胞 (HGF) 和乳腺癌细胞系 (MCF7) 的体外抗增殖作用。最后，进行了分子对接研究，以解释那些有助于区分选定的人碳酸酐酶同种型的结构要求。