2-(3-(piperidin-1-ylsulfonyl)benzamido)benzoic acid | 361989-72-2

• 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: 2-(3-(piperidin-1-ylsulfonyl)benzamido)benzoic acid
• 英文别名: 2-[(3-Piperidin-1-ylsulfonylbenzoyl)amino]benzoic acid
• CAS: 361989-72-2
• 化学式: C₁₉H₂₀N₂O₅S
• 分子量: 388.444
• InChiKey: ADZBCVAEFUXOEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-(1-磺酰基哌啶)-苯甲酸 在 吡啶 、 氯化亚砜 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 生成 2-(3-(piperidin-1-ylsulfonyl)benzamido)benzoic acid
  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

• CRTH2 Receptor Ligands For Therapeutic Use
  申请人：Ulven Trond

  公开号：US20090105218A1

  公开（公告）日：2009-04-23

  Compounds of formula (I) are useful in the treatment of disease responsive to modulation of CRTH2 receptor activity, wherein: A represents a carboxyl group —COOH, or a carboxyl bioisostere; L1 is a bond, —CH 2 —, —OCH 2 —, —CH 2 CH 2 — or —CH═CH—; L2 is CONH—, —NHCO—, SO 2 NR 1 —, —NR 1 SO 2 wherein R 1 is hydrogen or C 1 -C 3 alkyl, or a divalent radical of formula (X) or (Y), wherein ring Q is a non aromatic heterocyclic ring containing 5 to 7 ring atoms, including the nitrogen shown; L3 is a divalent linker radical of formula -(Alk 1 ) m -(Z) n -(Alk 2 ) p as defined in the description; ring Ar 1 is an optionally substituted divalent phenyl radical or divalent 5- or 6-membered monocyclic heteroaryl radical, in which L1 and the H[B] s L3L2Ar 2 CONH-radical are linked to adjacent ring carbon atoms; ring Ar 2 is an optionally substituted 1,3-phenylene radical, or an optionally substituted divalent 5- or 6-membered monocyclic heteroaryl radical, in which AL1Ar 1 NHCO-radical and the H[B] s L3L2-radical are linked to ring carbon atoms which are not in ortho relationship; ring B is as defined for Ar 2 , or an optionally substituted cycloalkyl, N-pyrrolidinyl, N-piperidinyl or N-azepinyl ring; and s is 0 or 1.

  公式（I）的化合物在治疗对CRTH2受体活性调节敏感的疾病中有用，其中：A代表羧基- COOH或羧基生物同位素; L1是键，-CH2-，-OCH2-，-CH2CH2-或-CH═CH-; L2是CONH-，-NHCO-，SO2NR1-，-NR1SO2其中R1是氢或C1-C3烷基，或式（X）或（Y）的双价基团，其中环Q是含有5至7个环原子的非芳香杂环环，包括所示的氮; L3是式-(Alk1)m-(Z)n-(Alk2)pas所定义的双价连接基团; 环Ar1是可选的取代的双价苯基团或双价的5-或6-成员的单环杂芳基团，其中L1和H[B]sL3L2Ar2CONH基团连接到相邻的环碳原子; 环Ar2是可选的取代的1,3-苯基基团，或可选的取代的双价5-或6-成员的单环杂芳基团，在其中AL1Ar1NHCO基团和H[B]sL3L2基团连接到不处于邻位关系的环碳原子; 环B如Ar2所定义，或可选的取代的环烷基，N-吡咯烷基，N-哌啶基或N-氮杂庚基; s为0或1。
• 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.