(4-(2'-methoxy-[1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-(4-(3-(prop-2-yn-1-yloxy)propyl)benzyl)piperidin-1-yl)methanone | 1476719-64-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (4-(2'-methoxy-[1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-(4-(3-(prop-2-yn-1-yloxy)propyl)benzyl)piperidin-1-yl)methanone
• 英文别名: [4-[4-(2-Methoxyphenyl)phenyl]triazol-1-yl]-[2-[[4-(3-prop-2-ynoxypropyl)phenyl]methyl]piperidin-1-yl]methanone；[4-[4-(2-methoxyphenyl)phenyl]triazol-1-yl]-[2-[[4-(3-prop-2-ynoxypropyl)phenyl]methyl]piperidin-1-yl]methanone
• CAS: 1476719-64-8
• 化学式: C₃₄H₃₆N₄O₃
• 分子量: 548.685
• InChiKey: BLKNHPNMTMTWKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  69.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-苄基哌啶 在 哌啶 、 盐酸 、 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 sodium iodate 、 硫酸 、 10 wt% Pd(OH)2 on carbon 、 氢气 、 碘 、 sodium hydride 、 溶剂黄146 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 44.5h， 生成 (4-(2'-methoxy-[1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-(4-(3-(prop-2-yn-1-yloxy)propyl)benzyl)piperidin-1-yl)methanone
  参考文献：
  名称：

  Development and Optimization of Piperidyl-1,2,3-Triazole Ureas as Selective Chemical Probes of Endocannabinoid Biosynthesis

  摘要：

  We have previously shown that 1,2,3-triazole ureas (1,2,3-TUs) act as versatile class of irreversible serine hydrolase inhibitors that can be tuned to create selective probes for diverse members of this large enzyme class, including diacylglycerol lipase-beta (DAGL beta), a principal biosynthetic enzyme for the endocannabinoid 2-arachidonoylglycerol (2-AG). Here, we provide a detailed account of the discovery, synthesis, and structure-activity relationship (SAR) of (2-substituted)-piperidyl-1,2,3-TUs that selectively inactivate DAGL beta in living systems. Key to success was the use of activity-based protein profiling (ABPP) with broad-spectrum and tailored activity-based probes to guide our medicinal chemistry efforts. We also describe an expanded repertoire of DAGL-tailored activity-based probes that includes biotinylated and alkyne agents for enzyme enrichment coupled with mass spectrometry-based proteomics and assessment of proteome-wide selectivity. Our findings highlight the broad utility of 1,2,3-TUs for serine hydrolase inhibitor development and their application to create selective probes of endocannabinoid biosynthetic pathways.

  DOI：

  10.1021/jm400898x

文献信息

• Development and Optimization of Piperidyl-1,2,3-Triazole Ureas as Selective Chemical Probes of Endocannabinoid Biosynthesis
  作者：Ku-Lung Hsu、Katsunori Tsuboi、Landon R. Whitby、Anna E. Speers、Holly Pugh、Jordon Inloes、Benjamin F. Cravatt

  DOI：10.1021/jm400898x

  日期：2013.11.14

  We have previously shown that 1,2,3-triazole ureas (1,2,3-TUs) act as versatile class of irreversible serine hydrolase inhibitors that can be tuned to create selective probes for diverse members of this large enzyme class, including diacylglycerol lipase-beta (DAGL beta), a principal biosynthetic enzyme for the endocannabinoid 2-arachidonoylglycerol (2-AG). Here, we provide a detailed account of the discovery, synthesis, and structure-activity relationship (SAR) of (2-substituted)-piperidyl-1,2,3-TUs that selectively inactivate DAGL beta in living systems. Key to success was the use of activity-based protein profiling (ABPP) with broad-spectrum and tailored activity-based probes to guide our medicinal chemistry efforts. We also describe an expanded repertoire of DAGL-tailored activity-based probes that includes biotinylated and alkyne agents for enzyme enrichment coupled with mass spectrometry-based proteomics and assessment of proteome-wide selectivity. Our findings highlight the broad utility of 1,2,3-TUs for serine hydrolase inhibitor development and their application to create selective probes of endocannabinoid biosynthetic pathways.