FE-GW405833 | 1246021-55-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: FE-GW405833
• 英文别名: 1-(2,3-dichlorobenzoyl)-5-(2-fluoroethoxy)-2-methyl-3-[2-(4-morpholinyl)ethyl]-1H-indole；(2,3-dichlorophenyl)(5-(2-fluoroethoxy)-2-methyl-3-(2-morpholinoethyl)-1H-indol-1-yl)methanone；(2,3-dichlorophenyl)-[5-(2-fluoroethoxy)-2-methyl-3-(2-morpholin-4-ylethyl)indol-1-yl]methanone
• CAS: 1246021-55-5
• 化学式: C₂₄H₂₅Cl₂FN₂O₃
• 分子量: 479.379
• InChiKey: MUXUBRNSJROXHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  43.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(2,3-dichlorobenzoyl)-5-methoxy-2-methyl-3-[2-(4-morpholinyl)ethyl]-1H-indole 在 三溴化硼 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 FE-GW405833
  参考文献：
  名称：

  Synthesis, in vitro and in vivo evaluation of fluorine-18 labelled FE-GW405833 as a PET tracer for type 2 cannabinoid receptor imaging

  摘要：

  The type 2 cannabinoid receptor (CB2R) is part of the endocannabinoid system and is expressed in tissues related to the immune system. As the CB2R has a very low brain expression in non-pathological conditions, but is upregulated in activated microglia, it is an interesting target for visualization of neuroinflammation using positron emission tomography with a suitable radiolabeled CB2R ligand. In this study, we radiolabelled a fluoroethyl derivative of GW405833, a well known CB2R partial agonist, with fluorine-18 (half-life 109.8 min) by alkylation of the phenol precursor with 1-bromo-2-[F-18] fluoroethane. In vitro studies showed that FE-GW405833 behaved as a selective high affinity (27 nM) inverse agonist for hCB(2)R. [F-18] FE-GW405833 showed moderate initial brain uptake in mice and rats, but a slow washout from brain and plasma due to retention of a radiometabolite. Specific binding of the tracer to human CB2R was demonstrated in vivo in a rat model with local CB2R overexpression in the brain. Optimized derivatives of GW405833 that are less susceptible to metabolism will need to be developed in order to provide a useful tracer for CB2R quantification with PET. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.033

文献信息

• Synthesis, in vitro and in vivo evaluation of fluorine-18 labelled FE-GW405833 as a PET tracer for type 2 cannabinoid receptor imaging
  作者：Nele Evens、Caroline Vandeputte、Giulio G. Muccioli、Didier M. Lambert、Veerle Baekelandt、Alfons M. Verbruggen、Zeger Debyser、Koen Van Laere、Guy M. Bormans

  DOI：10.1016/j.bmc.2011.06.033

  日期：2011.8

  The type 2 cannabinoid receptor (CB2R) is part of the endocannabinoid system and is expressed in tissues related to the immune system. As the CB2R has a very low brain expression in non-pathological conditions, but is upregulated in activated microglia, it is an interesting target for visualization of neuroinflammation using positron emission tomography with a suitable radiolabeled CB2R ligand. In this study, we radiolabelled a fluoroethyl derivative of GW405833, a well known CB2R partial agonist, with fluorine-18 (half-life 109.8 min) by alkylation of the phenol precursor with 1-bromo-2-[F-18] fluoroethane. In vitro studies showed that FE-GW405833 behaved as a selective high affinity (27 nM) inverse agonist for hCB(2)R. [F-18] FE-GW405833 showed moderate initial brain uptake in mice and rats, but a slow washout from brain and plasma due to retention of a radiometabolite. Specific binding of the tracer to human CB2R was demonstrated in vivo in a rat model with local CB2R overexpression in the brain. Optimized derivatives of GW405833 that are less susceptible to metabolism will need to be developed in order to provide a useful tracer for CB2R quantification with PET. (C) 2011 Elsevier Ltd. All rights reserved.