3-benzyl-5-methoxy-1,3,4-oxadiazol-2(3H)-one | 1473394-49-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-benzyl-5-methoxy-1,3,4-oxadiazol-2(3H)-one
• 英文别名: 3-Benzyl-5-methoxy-1,3,4-oxadiazol-2-one；3-benzyl-5-methoxy-1,3,4-oxadiazol-2-one
• CAS: 1473394-49-8
• 化学式: C₁₀H₁₀N₂O₃
• 分子量: 206.201
• InChiKey: AUPZIALIBFKSKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  51.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  methyl (benzylidene)carbazate 在 吡啶 、 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 生成 3-benzyl-5-methoxy-1,3,4-oxadiazol-2(3H)-one
  参考文献：
  名称：

  Chiral 1,3,4-Oxadiazol-2-ones as Highly Selective FAAH Inhibitors

  摘要：

  In the present study, identification of chiral 1,3,4-oxadiazol-2-ones as potent and selective FAAH inhibitors has been described. The separated enantiomers showed clear differences in the potency and selectivity toward both FAAH and MAGL. Additionally, the importance of the chirality on the inhibitory activity and selectivity was proven by the simplification approach by removing a methyl group at the 3-position of the 1,3,4-oxadiazol-2-one ring. The most potent compound of the series, the S-enantiomer of 3-(1-(4-isobutylphenyl)ethyl)-5-methoxy-1,3,4-oxadiazol-2(3H)-one (JZP-327A, 51), inhibited human recombinant FAAH (hrFAAH) in the low nanomolar range (IC50 = 11 nM), whereas its corresponding R-enantiomer 52 showed only moderate inhibition toward hrFAAH (IC50 = 0.24 mu M). In contrast to hrFAAH, R-enantiomer 52 was more potent in inhibiting the activity of hrMAGL compared to S-enantiomer 51 (IC50 = 4.0 mu M and 16% inhibition at 10 mu M, respectively). The FAAH selectivity of the compound Si over the supposed main off-targets, MAGL and COX, was found to be >900-fold. In addition, activity-based protein profiling (ABPP) indicated high selectivity over other serine hydrolases. Finally, the selected S-enantiomers 51, 53, and 55 were shown to be tight binding, slowly reversible inhibitors of the hrFAAH.

  DOI：

  10.1021/jm400923s

文献信息

• Chiral 1,3,4-Oxadiazol-2-ones as Highly Selective FAAH Inhibitors
  作者：Jayendra Z. Patel、Teija Parkkari、Tuomo Laitinen、Agnieszka A. Kaczor、Susanna M. Saario、Juha R. Savinainen、Dina Navia-Paldanius、Mariateresa Cipriano、Jukka Leppänen、Igor O. Koshevoy、Antti Poso、Christopher J. Fowler、Jarmo T. Laitinen、Tapio Nevalainen

  DOI：10.1021/jm400923s

  日期：2013.11.14

  In the present study, identification of chiral 1,3,4-oxadiazol-2-ones as potent and selective FAAH inhibitors has been described. The separated enantiomers showed clear differences in the potency and selectivity toward both FAAH and MAGL. Additionally, the importance of the chirality on the inhibitory activity and selectivity was proven by the simplification approach by removing a methyl group at the 3-position of the 1,3,4-oxadiazol-2-one ring. The most potent compound of the series, the S-enantiomer of 3-(1-(4-isobutylphenyl)ethyl)-5-methoxy-1,3,4-oxadiazol-2(3H)-one (JZP-327A, 51), inhibited human recombinant FAAH (hrFAAH) in the low nanomolar range (IC50 = 11 nM), whereas its corresponding R-enantiomer 52 showed only moderate inhibition toward hrFAAH (IC50 = 0.24 mu M). In contrast to hrFAAH, R-enantiomer 52 was more potent in inhibiting the activity of hrMAGL compared to S-enantiomer 51 (IC50 = 4.0 mu M and 16% inhibition at 10 mu M, respectively). The FAAH selectivity of the compound Si over the supposed main off-targets, MAGL and COX, was found to be >900-fold. In addition, activity-based protein profiling (ABPP) indicated high selectivity over other serine hydrolases. Finally, the selected S-enantiomers 51, 53, and 55 were shown to be tight binding, slowly reversible inhibitors of the hrFAAH.