(2,3-dichlorophenyl)[5-hydroxy-2-methyl-3-(2-(morpholin-4-yl)ethyl)indol-1-yl]methanone | 1246021-54-4

• 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: (2,3-dichlorophenyl)[5-hydroxy-2-methyl-3-(2-(morpholin-4-yl)ethyl)indol-1-yl]methanone
• 英文别名: 1-(2,3-dichlorobenzoyl)-5-hydroxy-2-methyl-3-[2-(4-morpholinyl)ethyl]-1H-indole；(2,3-dichlorophenyl)(5-hydroxy-2-methyl-3-(2-morpholinoethyl)-1H-indol-1-yl)methanone；(2,3-dichlorophenyl)-[5-hydroxy-2-methyl-3-(2-morpholin-4-ylethyl)indol-1-yl]methanone
• CAS: 1246021-54-4
• 化学式: C₂₂H₂₂Cl₂N₂O₃
• 分子量: 433.334
• InChiKey: QUKQTCPFSCZSOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  54.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2,3-dichlorophenyl)[5-hydroxy-2-methyl-3-(2-(morpholin-4-yl)ethyl)indol-1-yl]methanone 、 1-bromo-2-[¹⁸F]fluoroethane 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.03h， 生成 (2,3-dichlorophenyl)-[5-(2-(18F)fluoranylethoxy)-2-methyl-3-(2-morpholin-4-ylethyl)indol-1-yl]methanone
  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
• 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 、 甲醇 作用下， 以 二氯甲烷 为溶剂， 以62%的产率得到(2,3-dichlorophenyl)[5-hydroxy-2-methyl-3-(2-(morpholin-4-yl)ethyl)indol-1-yl]methanone
  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

• [EN] REPORTER GENE CONSTRUCTS FOR PET<br/>[FR] CONSTRUCTIONS DE GÈNE RAPPORTEUR POUR TEP
  申请人：KATHOLIEKE UNIVERSIFEIT LEUVEN

  公开号：WO2010105315A2

  公开（公告）日：2010-09-23

  The present invention relates to the field of in vivo molecular imaging and, more particularly to a method for reporter gene imaging via positron emission tomography (PET), which can be applied in nervous system (brain, cerebrum, cerebellum, medulla, pons, spinal cord, sciatic nerve) and particularly in the brain. The present invention also involves type 2 cannabinoid receptor (CB2) based reporter gene constructs and a reporter probe or tracer (reporter system) for use in a molecular imaging therapy for instance by PET. The reporter gene encodes the reporter protein to which the reporter probe binds.