(S)-N-(2-oxo-3-oxetanyl)-1-naphthamide | 1237534-71-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (S)-N-(2-oxo-3-oxetanyl)-1-naphthamide
• 英文别名: N-[(3S)-2-oxooxetan-3-yl]naphthalene-1-carboxamide
• CAS: 1237534-71-2
• 化学式: C₁₄H₁₁NO₃
• 分子量: 241.246
• InChiKey: MMOYWBVFBJQWKM-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 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：

  (S)-3-氨基-2-氧杂环酮对甲苯磺酸 、 1-萘甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以67%的产率得到(S)-N-(2-oxo-3-oxetanyl)-1-naphthamide
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of N-(2-Oxo-3-oxetanyl)amides as N-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm100582w

文献信息

• 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.