5-[4-(4-nitro-phenylcarbamoyl)-piperazin-1-yl]-benzofuran-2-carboxylic acid ethyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-[4-(4-nitro-phenylcarbamoyl)-piperazin-1-yl]-benzofuran-2-carboxylic acid ethyl ester
• 英文别名: Ethyl 5-[4-[(4-nitrophenyl)carbamoyl]piperazin-1-yl]-1-benzofuran-2-carboxylate；ethyl 5-[4-[(4-nitrophenyl)carbamoyl]piperazin-1-yl]-1-benzofuran-2-carboxylate
• 化学式: C₂₂H₂₂N₄O₆
• 分子量: 438.44
• InChiKey: XQRGFNIRTZIOKG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-氨基苯并呋喃甲酸乙酯 在 sodium carbonate 作用下， 以 丙醇 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 5-[4-(4-nitro-phenylcarbamoyl)-piperazin-1-yl]-benzofuran-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  An efficient synthesis and biological screening of benzofuran and benzo[ d ]isothiazole derivatives for Mycobacterium tuberculosis DNA GyrB inhibition

  摘要：

  A series of twenty eight molecules of ethyl 5-(piperazin-1-yl)benzofuran-2-carboxylate and 3-(piperazin-1-yl)benzo[d]isothiazole were designed by molecular hybridization of thiazole aminopiperidine core and carbamide side chain in eight steps and were screened for their in vitro Mycobacterium smegmatis (MS) GyrB ATPase assay, Mycobacterium tuberculosis (MTB) DNA gyrase super coiling assay, antitubercular activity, cytotoxicity and protein-inhibitor interaction assay through differential scanning fluorimetry. Also the orientation and the ligand-protein interactions of the top hit molecules with MS DNA gyrase B subunit active site were investigated applying extra precision mode (XP) of Glide. Among the compounds studied, 4-(benzo[d]isothiazol-3-yl)-N-(4-chlorophenyl)piperazine-1-carboxamide (26) was found to be the most promising inhibitor with an MS GyrB IC50 of 1.77 +/- 0.23 mu M, 0.42 +/- 0.23 against MTB DNA gyrase, MTB MIC of 3.64 mu M, and was not cytotoxic in eukaryotic cells at 100 mu M. Moreover the interaction of protein-ligand complex was stable and showed a positive shift of 3.5 degrees C in differential scanning fluorimetric evaluations. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.10.016

文献信息

• An efficient synthesis and biological screening of benzofuran and benzo[ d ]isothiazole derivatives for Mycobacterium tuberculosis DNA GyrB inhibition
  作者：Kummetha Indrasena Reddy、Konduri Srihari、Janupally Renuka、Komanduri Shruthi Sree、Aruna Chuppala、Variam Ullas Jeankumar、Jonnalagadda Padma Sridevi、Kondra Sudhakar Babu、Perumal Yogeeswari、Dharmarajan Sriram

  DOI：10.1016/j.bmc.2014.10.016

  日期：2014.12

  A series of twenty eight molecules of ethyl 5-(piperazin-1-yl)benzofuran-2-carboxylate and 3-(piperazin-1-yl)benzo[d]isothiazole were designed by molecular hybridization of thiazole aminopiperidine core and carbamide side chain in eight steps and were screened for their in vitro Mycobacterium smegmatis (MS) GyrB ATPase assay, Mycobacterium tuberculosis (MTB) DNA gyrase super coiling assay, antitubercular activity, cytotoxicity and protein-inhibitor interaction assay through differential scanning fluorimetry. Also the orientation and the ligand-protein interactions of the top hit molecules with MS DNA gyrase B subunit active site were investigated applying extra precision mode (XP) of Glide. Among the compounds studied, 4-(benzo[d]isothiazol-3-yl)-N-(4-chlorophenyl)piperazine-1-carboxamide (26) was found to be the most promising inhibitor with an MS GyrB IC50 of 1.77 +/- 0.23 mu M, 0.42 +/- 0.23 against MTB DNA gyrase, MTB MIC of 3.64 mu M, and was not cytotoxic in eukaryotic cells at 100 mu M. Moreover the interaction of protein-ligand complex was stable and showed a positive shift of 3.5 degrees C in differential scanning fluorimetric evaluations. (C) 2014 Elsevier Ltd. All rights reserved.