methyl 2-amino-6-methoxybenzoate hydrochloride | 1448009-40-2

• 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: methyl 2-amino-6-methoxybenzoate hydrochloride
• 英文别名: methyl 2-amino-6-methoxybenzoate;hydrochloride
• CAS: 1448009-40-2
• 化学式: C₉H₁₁NO₃*ClH
• 分子量: 217.652
• InChiKey: GYSPHNWNOAKZCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.49
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  61.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(N,N-diethylsulfamoyl)benzoyl chloride 、 methyl 2-amino-6-methoxybenzoate hydrochloride 在 吡啶 作用下， 生成 methyl 2-(3-(N,N-diethylsulfamoyl)benzamido)-6-methoxybenzoate
  参考文献：
  名称：

  Structure Optimization of 2-Benzamidobenzoic Acids as PqsD Inhibitors for Pseudomonas aeruginosa Infections and Elucidation of Binding Mode by SPR, STD NMR, and Molecular Docking

  摘要：

  Pseudomonas aeruginosa employs a characteristic pqs quorum sensing (QS) system that functions via the signal molecules PQS and its precursor HHQ, They control the production of a number of virulence factors and biofilm formation. Recently, we have shown that sulfonamide substituted 2-benzamidobenzoic acids, which are known FabH inhibitors, are also able to inhibit PqsD, the enzyme catalyzing the last and key step in the biosynthesis of HHQ, Here, we describe the further optimization and characterization of this class of compounds as PqsD inhibitors. Structural modifications showed that both the carboxylic acid ortho to the amide and 3'-sulfonamide are essential for binding. Introduction of substituents in the anthranilic part of the molecule resulted in compounds with IC50 values in the low micromolar range. Binding mode investigations by SPR with wild-type and mutated PqsD revealed that this compound class does not bind into the active center of PqsD but in the ACoA channel, preventing the substrate from accessing the active site. This binding mode was further confirmed by docking studies and STD NMR.

  DOI：

  10.1021/jm4006302

文献信息

• Benzoxazin-2-one, deren Herstellung und diese Verbindungen enthaltende Arzneimittel
  申请人：Dr. Karl Thomae GmbH

  公开号：EP0093922A2

  公开（公告）日：1983-11-16

  Neue Benzoxazin-2-one der allgemeinen Formel in der A ein Schwefelatom, eine SO-, SO,-, R-N=S- oder R-N=SO-Gruppe, wobei R ein Wasserstoffatom oder eine Acylgruppe darstellt, D eine Alkylengruppe, R, eine Alkyl-, Phenylalkyl-, Cycloalkyl- oder Phenylgruppe, R. ein Wasserstoffatom oder eine Alkylgruppe, Ra ein Wasserstoffatom- oder Halogenatom, eine Nitro-oder Alkylgruppe und R6 ein Wasserstoff- oder Halogenatom oder eine Alkylgruppe bedeuten, welche wertvolle pharmakologische Eigenschaften aufweisen, insbesondere antithrombotische Wirkungen. Die Verbindungen der allgemeinen Formel I können nach für analog Verbindungen üblichen Verfahren hergestellt werden.

  新的通式苯并恶嗪-2-酮 中的 A 代表硫原子、SO、SO,-、R-N=S 或 R-N=SO 基团，其中 R 代表氢原子或酰基、 D 是亚烷基、 R、烷基、苯烷基、环烷基或苯基、 R 代表氢原子或烷基、 Ra 代表氢原子或卤素原子、硝基或烷基，以及 R6 是氢原子、卤素原子或烷基，它们具有重要的药理特性，特别是抗血栓作用。 通式 I 的化合物可以按照类似化合物的常规方法制备。
• US4518597A
  申请人：——

  公开号：US4518597A

  公开（公告）日：1985-05-21
• Structure Optimization of 2-Benzamidobenzoic Acids as PqsD Inhibitors for Pseudomonas aeruginosa Infections and Elucidation of Binding Mode by SPR, STD NMR, and Molecular Docking
  作者：Elisabeth Weidel、Johannes C. de Jong、Christian Brengel、Michael P. Storz、Andrea Braunshausen、Matthias Negri、Alberto Plaza、Anke Steinbach、Rolf Müller、Rolf W. Hartmann

  DOI：10.1021/jm4006302

  日期：2013.8.8

  Pseudomonas aeruginosa employs a characteristic pqs quorum sensing (QS) system that functions via the signal molecules PQS and its precursor HHQ, They control the production of a number of virulence factors and biofilm formation. Recently, we have shown that sulfonamide substituted 2-benzamidobenzoic acids, which are known FabH inhibitors, are also able to inhibit PqsD, the enzyme catalyzing the last and key step in the biosynthesis of HHQ, Here, we describe the further optimization and characterization of this class of compounds as PqsD inhibitors. Structural modifications showed that both the carboxylic acid ortho to the amide and 3'-sulfonamide are essential for binding. Introduction of substituents in the anthranilic part of the molecule resulted in compounds with IC50 values in the low micromolar range. Binding mode investigations by SPR with wild-type and mutated PqsD revealed that this compound class does not bind into the active center of PqsD but in the ACoA channel, preventing the substrate from accessing the active site. This binding mode was further confirmed by docking studies and STD NMR.