1-({[5-(aminosulfonyl)-3-(2-chlorophenyl)-1H-indol-2-yl]carbonyl}amino)-2,4,6-trimethylpyridinium perchlorate | 1160038-43-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-({[5-(aminosulfonyl)-3-(2-chlorophenyl)-1H-indol-2-yl]carbonyl}amino)-2,4,6-trimethylpyridinium perchlorate
• 英文别名: 3-(2-chlorophenyl)-5-sulfamoyl-N-(2,4,6-trimethylpyridin-1-ium-1-yl)-1H-indole-2-carboxamide;perchlorate
• CAS: 1160038-43-6
• 化学式: C₂₃H₂₂ClN₄O₃S*ClO₄
• 分子量: 569.422
• InChiKey: RYGGOOLZVZYLTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.02
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  192
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-(2-chlorophenyl)-2-(hydrazinocarbonyl)-1H-indole-5-sulfonamide 、 2,4,6-三甲基吡喃鎓高氯酸盐 在 高氯酸 作用下， 以 甲醇 、 水 为溶剂， 生成 1-({[5-(aminosulfonyl)-3-(2-chlorophenyl)-1H-indol-2-yl]carbonyl}amino)-2,4,6-trimethylpyridinium perchlorate
  参考文献：
  名称：

  Carbonic anhydrase inhibitors. Synthesis of 2,4,6-trimethylpyridinium derivatives of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides acting as potent inhibitors of the tumor-associated isoform IX and XII

  摘要：

  A series of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides possessing various 2-, 3- or 4- substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, or a perfluorophenyl moiety, has been derivatized by reaction with 2,4,6-trimethylpyrylium perchlorate. The new sulfonamides were evaluated as inhibitors of four mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that is, CA I, II (cytosolic), CA IX and XII (transmembrane, tumor-associated forms). Excellent inhibitory activity was observed against hCA IX with most of these sulfonamides, and against hCA XII with some of the new compounds. These compounds were generally less effective inhibitors of hCA II. Being membrane impermeant, these positively-charged sulfonamides are interesting candidates for targeting the tumor-associated CA IX and XII, as possible diagnostic tools or therapeutic agents. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.04.068

文献信息

• Carbonic anhydrase inhibitors. Synthesis of 2,4,6-trimethylpyridinium derivatives of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides acting as potent inhibitors of the tumor-associated isoform IX and XII
  作者：Özlen Güzel、Alfonso Maresca、Andrea Scozzafava、Aydın Salman、Alexandru T. Balaban、Claudiu T. Supuran

  DOI：10.1016/j.bmcl.2009.04.068

  日期：2009.6

  A series of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides possessing various 2-, 3- or 4- substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, or a perfluorophenyl moiety, has been derivatized by reaction with 2,4,6-trimethylpyrylium perchlorate. The new sulfonamides were evaluated as inhibitors of four mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that is, CA I, II (cytosolic), CA IX and XII (transmembrane, tumor-associated forms). Excellent inhibitory activity was observed against hCA IX with most of these sulfonamides, and against hCA XII with some of the new compounds. These compounds were generally less effective inhibitors of hCA II. Being membrane impermeant, these positively-charged sulfonamides are interesting candidates for targeting the tumor-associated CA IX and XII, as possible diagnostic tools or therapeutic agents. (C) 2009 Elsevier Ltd. All rights reserved.
• Discovery of Low Nanomolar and Subnanomolar Inhibitors of the Mycobacterial β-Carbonic Anhydrases Rv1284 and Rv3273
  作者：Özlen Güzel、Alfonso Maresca、Andrea Scozzafava、Aydın Salman、Alexandru T. Balaban、Claudiu T. Supuran

  DOI：10.1021/jm9004016

  日期：2009.7.9

  A series of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides has been derivatized by reaction with 2,4,6-trimethylpyrylium perchlorate, leading to pyridinium derivatives. The new sulfonamides were evaluated as inhibitors of two beta-carbonic anhydrases (CAs, EC 4.2.1.1) from Mycobaterium tuberculosis, Rv1284 and Rv3273. The whole series showed excellent nanomolar inhibitory activity, with several subnanomolar inhibitors being detected. Rv1284 and Rv3273 have potential for developing antimycobacterial agents with an alternate mechanism of action.