N-[(E)-(2,4-dichlorophenyl)methylideneamino]-4-hydroxy-3-methoxybenzamide | 1415691-65-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: N-[(E)-(2,4-dichlorophenyl)methylideneamino]-4-hydroxy-3-methoxybenzamide
• CAS: 1415691-65-4
• 化学式: C₁₅H₁₂Cl₂N₂O₃
• 分子量: 339.178
• InChiKey: MDKHPTGLOBHVDN-QGMBQPNBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  70.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  香草酸 在 硫酸 、 一水合肼 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 生成 N-[(E)-(2,4-dichlorophenyl)methylideneamino]-4-hydroxy-3-methoxybenzamide
  参考文献：
  名称：

  Design, synthesis and antibacterial activities of vanillic acylhydrazone derivatives as potential β-ketoacyl-acyl carrier protein synthase III (FabH) inhibitors

  摘要：

  Fatty acid biosynthesis is essential for bacterial survival. FabH, beta-ketoacyl-acyl carrier protein (ACP) synthase III, is a particularly attractive target, since it is central to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and Gram-negative bacteria. A series of acylhydrazone derivatives were synthesized and developed as potent inhibitors of FabH. This inhibitor class demonstrates strong broad-spectrum antibacterial activity. Compounds with potent antibacterial activities were tested for their Escherichia coli FabH inhibitory activity. Especially, compound E9 showed the most potent antibacterial activity with MIC values of 0.39-1.56 mu g/mL against the tested bacterial strains and exhibited the most potent E. coli FabH inhibitory activity with IC50 of 2.5 mu M. Docking simulation was performed to position compound E9 into the E. coli FabH active site to determine the probable binding conformation. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.09.009

文献信息

• [EN] SMALL MOLECULE MALARIAL ALDOLASE-TRAP ENHANCERS AND GLIDEOSOME INHIBITORS<br/>[FR] ACTIVATEURS À PETITES MOLÉCULES D'ALDOLASE-TRAP DE LA MALARIA ET INHIBITEURS DU GLIDÉOSOME
  申请人：UNIV NEW YORK

  公开号：WO2013063243A1

  公开（公告）日：2013-05-02

  In one aspect, the present invention relates to a method of identifying compounds useful in modifying the activity of Aldolase. The method includes providing a first model comprising Aldolase or residues of the amino acid sequence corresponding to SEQ ID NO: 1 said residues being at amino acid positions selected from the group consisting of 10-13, 26, 27, 29, 30, 31, 32, 33, 37, 39, 40, 41, 43, 44, 47, 48, 51, 52, 60, 63, 66, 79, 84, 85, 92, 93, 103, 106-109, 112-117, 138, 142, 146, 148, 151, 153, 179, 182, 183, 185, 186, 194, 196, 197, 198, 199, 208, 226-228, 231- 269, 270, 272, 277-283, 285-289, 294, 295, 297-299, 301-304, 306-310, 312, 313, 316, 317, 319, 321, 323, 326, 330, 344, 345, and 347, providing one or more candidate compounds, evaluating contact between the candidate compounds and the first model to determine which of the one or more candidate compounds have an ability to bind to and/or fit in the first model, and identifying compounds which, based on said evaluating, have the ability to bind to and/or fit in the first model as compounds potentially useful for modifying the activity of Aldolase. The present invention also discloses compounds and compositions which modify the activity of Aldolase, or a complex between Aldolase and TRAP. Methods of treating or preventing malaria, or an infection by apicomplexan organisms are also disclosed.

  在一个方面，本发明涉及一种识别有助于修改Aldolase活性的化合物的方法。该方法包括提供一个第一模型，该模型包括Aldolase或者与SEQ ID NO: 1相对应的氨基酸序列残基，所述残基位于氨基酸位置中的一个或多个位置，所选位置包括10-13、26、27、29、30、31、32、33、37、39、40、41、43、44、47、48、51、52、60、63、66、79、84、85、92、93、103、106-109、112-117、138、142、146、148、151、153、179、182、183、185、186、194、196、197、198、199、208、226-228、231-269、270、272、277-283、285-289、294、295、297-299、301-304、306-310、312、313、316、317、319、321、323、326、330、344、345和347，提供一个或多个候选化合物，评估候选化合物与第一模型之间的接触，以确定哪些候选化合物具有结合和/或适配第一模型的能力，并识别化合物，这些化合物根据所述评估具有结合和/或适配第一模型的能力，可能有助于修改Aldolase活性。本发明还公开了修改Aldolase活性的化合物和组合物，或者Aldolase和TRAP之间的复合物。还公开了治疗或预防疟疾或被顶复门原生生物感染的方法。
• US20140275088A1
  申请人：——

  公开号：US20140275088A1

  公开（公告）日：2014-09-18
• US9873661B2
  申请人：——

  公开号：US9873661B2

  公开（公告）日：2018-01-23
• Design, synthesis and antibacterial activities of vanillic acylhydrazone derivatives as potential β-ketoacyl-acyl carrier protein synthase III (FabH) inhibitors
  作者：Xiao-Liang Wang、Yan-Bin Zhang、Jian-Feng Tang、Yu-Shun Yang、Ruo-Qi Chen、Fei Zhang、Hai-Liang Zhu

  DOI：10.1016/j.ejmech.2012.09.009

  日期：2012.11

  Fatty acid biosynthesis is essential for bacterial survival. FabH, beta-ketoacyl-acyl carrier protein (ACP) synthase III, is a particularly attractive target, since it is central to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and Gram-negative bacteria. A series of acylhydrazone derivatives were synthesized and developed as potent inhibitors of FabH. This inhibitor class demonstrates strong broad-spectrum antibacterial activity. Compounds with potent antibacterial activities were tested for their Escherichia coli FabH inhibitory activity. Especially, compound E9 showed the most potent antibacterial activity with MIC values of 0.39-1.56 mu g/mL against the tested bacterial strains and exhibited the most potent E. coli FabH inhibitory activity with IC50 of 2.5 mu M. Docking simulation was performed to position compound E9 into the E. coli FabH active site to determine the probable binding conformation. (C) 2012 Elsevier Masson SAS. All rights reserved.