(S)-N-(2-oxooxetan-3-yl)biphenyl-4-carboxamide | 1142079-64-8

• 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-oxooxetan-3-yl)biphenyl-4-carboxamide
• 英文别名: (S)-N-(2-oxo-3-oxetanyl)biphenyl-4-carboxamide；N-[(3S)-2-oxooxetan-3-yl]-4-phenylbenzamide
• CAS: 1142079-64-8
• 化学式: C₁₆H₁₃NO₃
• 分子量: 267.284
• InChiKey: PGKVFBCLXQUHRC-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 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：

  联苯-4-甲酰氯 、 (S)-3-氨基-2-氧杂环酮对甲苯磺酸 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 (S)-N-(2-oxooxetan-3-yl)biphenyl-4-carboxamide
  参考文献：
  名称：

  Compositions and methods of inhibiting N-acylethanolamine-hydrolyzing acid amidase

  摘要：

  考虑到抑制N-酰基乙醇胺水解酸酰胺酶（NAAA）的化合物和药物组合物，以增加NAAA底物棕榈醇胺（PEA）的浓度。考虑到NAAA的抑制对于缓解与PEA浓度降低相关的症状是有效的。除其他用途外，各种NAAA抑制剂特别被考虑作为治疗炎症性疾病的治疗药物。

  公开号：

  US09321743B2

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：US20140094508A1

  公开（公告）日：2014-04-03

  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-乙醇胺水解酸酰胺酶（NAAA）的化合物和制药组合物，以增加NAAA底物棕榈酰乙醇胺（PEA）的浓度。本发明认为NAAA抑制对于缓解与PEA浓度降低相关的病症是有效的。此外，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。
• 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.
• US9321743B2
  申请人：——

  公开号：US9321743B2

  公开（公告）日：2016-04-26