4-((5-methoxy-2-oxo-1,3,4-oxadiazol-3(2H)-yl)methyl)benzonitrile

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((5-methoxy-2-oxo-1,3,4-oxadiazol-3(2H)-yl)methyl)benzonitrile
• 英文别名: 4-[(5-Methoxy-2-oxo-1,3,4-oxadiazol-3-yl)methyl]benzonitrile；4-[(5-methoxy-2-oxo-1,3,4-oxadiazol-3-yl)methyl]benzonitrile
• 化学式: C₁₁H₉N₃O₃
• 分子量: 231.211
• InChiKey: RBOBYNTWWPWICJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  74.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氰基苯甲醛 在 吡啶 、 sodium cyanoborohydride 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 生成 4-((5-methoxy-2-oxo-1,3,4-oxadiazol-3(2H)-yl)methyl)benzonitrile
  参考文献：
  名称：

  Revisiting 1,3,4-Oxadiazol-2-ones: Utilization in the Development of ABHD6 Inhibitors

  摘要：

  This article describes our systematic approach to exploring the utility of the 1,3,4-oxadiazol-2-one scaffold in the development of ABHD6 inhibitors. Compound 3-(3-aminobenzyl)-5-methoxy-1,3,4-oxadiazol-2(3H)-one (JZP-169, 52) was identified as a potent inhibitor of hABHD6, with an IC50 value of 216 nM. This compound at 10 mu M concentration did not inhibit any other endocannabinoid hydrolases, such as FAAH, MAGL and ABHD12, or bind to the cannabinoid receptors (CB1 and CB2). Moreover, in competitive activity-based protein profiling (ABPP), compound 52 (JZP-169) at 10 mu M selectively targeted ABHD6 of the serine hydrolases of mouse brain membrane proteome. Reversibility studies indicated that compound 52 inhibited hABHD6 in an irreversible manner. Finally, homology modelling and molecular docking studies were used to gain insights into the binding of compound 52 to the active site of hABHD6. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.08.030

文献信息

• Revisiting 1,3,4-Oxadiazol-2-ones: Utilization in the Development of ABHD6 Inhibitors
  作者：Jayendra Z. Patel、John van Bruchem、Tuomo Laitinen、Agnieszka A. Kaczor、Dina Navia-Paldanius、Teija Parkkari、Juha R. Savinainen、Jarmo T. Laitinen、Tapio J. Nevalainen

  DOI：10.1016/j.bmc.2015.08.030

  日期：2015.10

  This article describes our systematic approach to exploring the utility of the 1,3,4-oxadiazol-2-one scaffold in the development of ABHD6 inhibitors. Compound 3-(3-aminobenzyl)-5-methoxy-1,3,4-oxadiazol-2(3H)-one (JZP-169, 52) was identified as a potent inhibitor of hABHD6, with an IC50 value of 216 nM. This compound at 10 mu M concentration did not inhibit any other endocannabinoid hydrolases, such as FAAH, MAGL and ABHD12, or bind to the cannabinoid receptors (CB1 and CB2). Moreover, in competitive activity-based protein profiling (ABPP), compound 52 (JZP-169) at 10 mu M selectively targeted ABHD6 of the serine hydrolases of mouse brain membrane proteome. Reversibility studies indicated that compound 52 inhibited hABHD6 in an irreversible manner. Finally, homology modelling and molecular docking studies were used to gain insights into the binding of compound 52 to the active site of hABHD6. (C) 2015 Elsevier Ltd. All rights reserved.