(S)-N-(2-oxo-3-oxetanyl)-3-heptanamide | 1142079-56-8

• 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: (S)-N-(2-oxo-3-oxetanyl)-3-heptanamide
• 英文别名: N-[(3S)-2-oxooxetan-3-yl]heptanamide
• CAS: 1142079-56-8
• 化学式: C₁₀H₁₇NO₃
• 分子量: 199.25
• InChiKey: SNZBAKDOWBDCRQ-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 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：

  庚酰氯 、 (S)-3-氨基-2-氧杂环酮对甲苯磺酸 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以49%的产率得到(S)-N-(2-oxo-3-oxetanyl)-3-heptanamide
  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

• COMPOSITIONS AND METHODS OF INHIBITING N-ACYLETHANOLAMINE-HYDROLYZING ACID AMIDASE
  申请人：The Regents of the University of California

  公开号：US20160256432A1

  公开（公告）日：2016-09-08

  Compounds and pharmaceutical compositions are contemplated that inhibit N-acyl-ethanolamine-hydrolyzing acid amidase (NAAA) to so increase the concentration of the substrate of NAAA, palmitoylethanolamide (PEA). NAAA inhibition is contemplated to be effective to alleviate conditions associated with a reduced concentration of PEA. Among other uses, various NAAA inhibitors are especially contemplated as therapeutic agents in the treatment of inflammatory diseases.

  本文考虑研制抑制N-酰基-乙醇胺水解酸酶（NAAA）的化合物和药物组合物，以增加NAAA的底物棕榈酰乙醇胺（PEA）的浓度。考虑到NAAA的抑制是有效缓解与PEA浓度降低有关的疾病的条件。除其他用途外，各种NAAA抑制剂尤其被认为是治疗炎症性疾病的治疗剂。
• Inhibitors of NAAA and Methods Thereof
  申请人：Piomelli Daniele

  公开号：US20100311711A1

  公开（公告）日：2010-12-09

  Compounds and pharmaceutical compositions are contemplated that inhibit N-acyl-ethanolamine-hydrolyzing acid amidase (NAAA) to so increase the concentration of the substrate of NAAA, palmitoylethanolamide (PEA). NAAA inhibition is contemplated to be effective to alleviate conditions associated with a reduced concentration of PEA. Among other uses, various NAAA inhibitors are especially contemplated as therapeutic agents in the treatment of inflammatory diseases.

  本发明涉及抑制N-酰基-乙醇胺水解酸酶（NAAA）的化合物和药物组合物，以增加NAAA的底物棕榈酰乙醇胺（PEA）的浓度。本发明认为抑制NAAA有效缓解与PEA浓度降低相关的病症。此外，各种NAAA抑制剂特别被认为是治疗炎症性疾病的治疗剂。
• Compositions and methods of inhibiting N-acylethanolamine-hydrolyzing acid amidase
  申请人：The Regents of the University of California

  公开号：US10363237B2

  公开（公告）日：2019-07-30

  Compounds and pharmaceutical compositions are contemplated that inhibit N-acyl-ethanolamine-hydrolyzing acid amidase (NAAA) to so increase the concentration of the substrate of NAAA, palmitoylethanolamide (PEA). NAAA inhibition is contemplated to be effective to alleviate conditions associated with a reduced concentration of PEA. Among other uses, various NAAA inhibitors are especially contemplated as therapeutic agents in the treatment of inflammatory diseases.

  考虑使用抑制 N-酰基乙醇胺水解酸酰胺酶（NAAA）的化合物和药物组合物，以提高 NAAA 底物棕榈酰乙醇酰胺（PEA）的浓度。NAAA 抑制可有效缓解与 PEA 浓度降低有关的状况。除其他用途外，特别考虑将各种 NAAA 抑制剂作为治疗炎症性疾病的治疗剂。
• US9321743B2
  申请人：——

  公开号：US9321743B2

  公开（公告）日：2016-04-26
• 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.