N-(3-phenylpropanoyl)-L-homoserine lactone | 959613-40-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(3-phenylpropanoyl)-L-homoserine lactone
• 英文别名: (S)-N-(2-oxotetrahydrofuran-3-yl)-3-phenylpropionamide；3-phenylpropanoyl-L-HSL；3-pherylpropanoyl-L-HSL；N-[(3S)-2-oxooxolan-3-yl]-3-phenylpropanamide
• CAS: 959613-40-2
• 化学式: C₁₃H₁₅NO₃
• 分子量: 233.267
• InChiKey: RUQJSJHHSDXJNE-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  高丝氨酸内酯氢溴酸盐 、 3-苯基丙酸 在 PS-carbodiimide resin 作用下， 以 二氯甲烷 为溶剂， 以23.4%的产率得到N-(3-phenylpropanoyl)-L-homoserine lactone
  参考文献：
  名称：

  微波合成和评估作为最小化激活铜绿假单胞菌群体感应途径的抗癌化合物的苯甲基高丝氨酸内酯。

  摘要：

  细菌群体感应（QS）信号分子3-氧代-十二烷酰基-1-高丝氨酸内酯（OdDHL）由机会病原体铜绿假单胞菌产生，并控制与免疫受损个体中威胁生命的感染相关的毒力因子的表达。OdDHL还显示出抗癌活性，但具有增强铜绿假单胞菌致病性的能力。作为潜在的抗癌药，需要进一步考虑。为了寻找选择性抑制癌细胞生长的酰基高丝氨酸内酯，已通过微波合成制备了苯甲基高丝氨酸内酯类似物的文库，并评估了其对癌症生长的抑制作用和群体感应激活。SAR对比分析表明，抗癌和QS信号系统均需要长酰基侧链，并带有3-氧代取代基才能发挥最大活性。化合物12b 3-氧代-12-苯基十二烷酰基-1-高丝氨酸内酯被鉴定为具有强大的癌症生长抑制活性的前导化合物，该活性使铜绿假单胞菌报道基因分析中QS信号通路的激活最小化。

  DOI：

  10.1021/jm8015377

文献信息

• β‐Cyclodextrin Encapsulation of Synthetic AHLs: Drug Delivery Implications and Quorum‐Quenching Exploits
  作者：Eric W. Ziegler、Alan B. Brown、Nasri Nesnas、Christopher D. Chouinard、Anil K. Mehta、Andrew G. Palmer

  DOI：10.1002/cbic.202000773

  日期：2021.4.6

  A solution solution: Synthetic AHL analogues (SAHLAs) have demonstrated efficacy as quorum sensing inhibitors by receptor antagonism. However, like native AHLs, these compounds are poorly soluble. To improve their solubility, we investigated the association of three representative SAHLAs, and their hydrolysis products, with β‐cyclodextrin by spectrofluorimetry and evaluated co‐application of CDs with

  解决方案：合成 AHL 类似物 (SAHLA) 已通过受体拮抗作用证明作为群体感应抑制剂的功效。然而，与天然 AHL 一样，这些化合物的溶解性较差。为了提高它们的溶解度，我们通过荧光光谱法研究了三种代表性 SAHLA 及其水解产物与 β-环糊精的关联，并评估了 CD 与 SAHLA 在秀丽隐杆线虫感染模型中的共同应用。合成 AHL 的 β-环糊精封装（Palmer @FloridaTech）
• Synthesis and Structure−Activity Relationships of <i>N</i>-(2-Oxo-3-oxetanyl)amides as <i>N</i>-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors
  作者：Carlos Solorzano、Francesca Antonietti、Andrea Duranti、Andrea Tontini、Silvia Rivara、Alessio Lodola、Federica Vacondio、Giorgio Tarzia、Daniele Piomelli、Marco Mor

  DOI：10.1021/jm100582w

  日期：2010.8.12

  The fatty acid ethanolamides (FAEs) are a family of bioactive lipid mediators that include the endogenous agonist of peroxisome proliferator-activated receptor-alpha, palmitoylethanolamide (PEA). FAEs are hydrolyzed intracellularly by either fatty acid amide hydrolase or N-acylethanolamine-hydrolyzing acid amidase (NAAA). Selective inhibition of NAAA by (S)-N-(2-oxo-3-oxetanyl)-3-phenylpropionamide [(S)-OOPP, 7a] prevents PEA degradation in mouse leukocytes and attenuates responses to proinflammatory stimuli. Starting from the structure of 7a, a series of beta-lactones was prepared and tested on recombinant rat NAAA to explore structure-activity relationships (SARs) for this class of inhibitors and improve their in vitro potency. Following the hypothesis that these compounds inhibit NAAA by acylation of the catalytic cysteine, we identified several requirements for recognition at the active site and obtained new potent inhibitors. In particular, (S)-N-(2-oxo-3-oxetanyl)biphenyl-4-carboxamide (7h) was more potent than 7a at inhibiting recombinant rat NAAA activity (7a, IC(50) = 420 nM; 7h, IC(50) = 115 nM) in vitro and at reducing carrageenan-induced leukocyte infiltration in vivo.
• COMBINATIONS OF INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
  申请人：MERCK & CO., INC.

  公开号：EP0836383A1

  公开（公告）日：1998-04-22
• Modulation of Bacterial Quorum Sensing With Synthetic Ligands
  申请人：WISCONSIN ALUMNI RESEARCH FOUNDATION

  公开号：US20200115356A1

  公开（公告）日：2020-04-16

  The present invention provides compounds and methods for modulation of the quorum sensing of bacteria. In an embodiment, the compounds of the present invention are able to act as replacements for naturally occurring bacterial quorum sensing ligands in a ligand-protein binding system; that is, they imitate the effect of natural ligands and produce an agonistic effect. In another embodiment, the compounds of the present invention are able to act in a manner which disturbs or inhibits the naturally occurring ligand-protein binding system in quorum sensing bacteria; that is, they produce an antagonistic effect. The compounds of the present invention comprise N-acylated-homoserine lactones (AHLs) comprised of a wide range of acyl groups.
• MODULATION OF BACTERIAL QUORUM SENSING WITH SYNTHETIC LIGANDS
  申请人：WISCONSIN ALUMNI RESEARCH FOUNDATION

  公开号：US20220411390A1

  公开（公告）日：2022-12-29

  The present invention provides compounds and methods for modulation of the quorum sensing of bacteria. In an embodiment, the compounds of the present invention are able to act as replacements for naturally occurring bacterial quorum sensing ligands in a ligand-protein binding system; that is, they imitate the effect of natural ligands and produce an agonistic effect. In another embodiment, the compounds of the present invention are able to act in a manner which disturbs or inhibits the naturally occurring ligand-protein binding system in quorum sensing bacteria; that is, they produce an antagonistic effect. The compounds of the present invention comprise N-acylated-homoserine lactones (AHLs) comprised of a wide range of acyl groups.