9-(2-benzyloxy-ethyl)-7-fluoro-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide | 1246453-97-3

• 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: 9-(2-benzyloxy-ethyl)-7-fluoro-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide
• 英文别名: 9-(2-benzyloxyethyl)-7-fluoro-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide；N,N-diethyl-7-fluoro-9-(2-phenylmethoxyethyl)-1,2,3,4-tetrahydrocarbazole-4-carboxamide
• CAS: 1246453-97-3
• 化学式: C₂₆H₃₁FN₂O₂
• 分子量: 422.543
• InChiKey: KIJQSUXDWYVRPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  34.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  9-(2-benzyloxy-ethyl)-7-fluoro-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 methanesulfonic acid 2-(4-diethylcarbamoyl-7-fluoro-1,2,3,4-tetrahydro-carbazol-9-yl)-ethyl ester
  参考文献：
  名称：

  [18F]GE-180: A novel fluorine-18 labelled PET tracer for imaging Translocator protein 18kDa (TSPO)

  摘要：

  A series of tricyclic compounds have been synthesised and evaluated in vitro for affinity against Translocator protein 18 kDa (TSPO) and for preferred imaging properties. The most promising of the compounds were radiolabelled and evaluated in vivo to determine biodistribution and specificity for high expressing TSPO regions. Metabolite profiling in brain and plasma was also investigated. Evaluation in an autoradiography model of neuroinflammation was also carried out for the best compound, 12a ([F-18]GE-180). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.084
• 作为产物：
  描述：

  3-bromo-2-hydroxy-cyclohex-1-enecarboxylic acid ethyl ester 在 草酰氯 、 水 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 9-(2-benzyloxy-ethyl)-7-fluoro-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide
  参考文献：
  名称：

  [18F]GE-180: A novel fluorine-18 labelled PET tracer for imaging Translocator protein 18kDa (TSPO)

  摘要：

  A series of tricyclic compounds have been synthesised and evaluated in vitro for affinity against Translocator protein 18 kDa (TSPO) and for preferred imaging properties. The most promising of the compounds were radiolabelled and evaluated in vivo to determine biodistribution and specificity for high expressing TSPO regions. Metabolite profiling in brain and plasma was also investigated. Evaluation in an autoradiography model of neuroinflammation was also carried out for the best compound, 12a ([F-18]GE-180). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.084
• 作为试剂：
  描述：

  3-bromo-2-oxocyclohexanecarboxylic acid diethylamide 、 (2-benzyloxy-ethyl)-(3-fluoro-phenyl)-amine 在 氯化锌 氮气 、 乙酸乙酯 、 盐酸 、 水 、 potassium carbonate 、 crude material 、 silica gel 、 petrol 、 9-(2-benzyloxy-ethyl)-7-fluoro-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide 作用下， 以 异丙醇 为溶剂， 反应 19.0h， 以to afford 1.3 g (30%) of 9-(2-benzyloxy-ethyl)-5-fluoro-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide (41) along with the isomer 9-(2-benzyloxy-ethyl)-7-fluoro-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide as a mixture which的产率得到9-(2-benzyloxy-ethyl)-5-fluoro-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide
  参考文献：
  名称：

  INDOLE DERIVATIVES

  摘要：

  本发明提供了一种基于吲哚的体内成像剂，该成像剂与PBR结合亲和力高，给药后对大脑具有良好的摄取，并具有良好的选择性结合PBR。本发明还包括一种用于合成本发明的体内成像剂的前体化合物，以及一种用于合成该体内成像剂的方法，包括使用该前体化合物，以及用于执行该方法的套件。此外，还提供了一种用于自动合成体内成像剂的盒式装置。本发明的进一步方面包括包含本发明的体内成像剂的放射性药物组合物，以及使用该体内成像剂的方法。

  公开号：

  US20120020884A1

文献信息

• In vivo imaging method for cancer
  申请人：Jones Paul Alexander

  公开号：US09314541B2

  公开（公告）日：2016-04-19

  The present invention provides a method useful in the diagnosis and monitoring of cancer wherein there is an abnormal expression of PBR. The method of the invention is particularly useful in evaluating the severity of the cancer, e.g. PBR expression correlates with cell proliferation rates, metastatic potential, tumor aggressiveness, malignancy progression. The method of the invention can therefore be applied in the determination of likely disease progression and in making an associated prognosis. Furthermore, the method of the invention can find use in determining the likely success of certain therapeutic approaches, or in the evaluation of the efficacy of certain proposed new treatments.

  本发明提供了一种在癌症的诊断和监测中有用的方法，其中PBR的表达异常。本发明的方法特别适用于评估癌症的严重程度，例如PBR表达与细胞增殖率、转移潜力、肿瘤侵袭性、恶性进展相关。因此，本发明的方法可以应用于确定可能的疾病进展，并作出相关的预后。此外，本发明的方法可以用于确定某些治疗方法的成功可能性，或评估某些提议的新治疗方法的有效性。
• IN VIVO IMAGING METHOD OF MOOD DISORDERS
  申请人：Jones Paul Alexander

  公开号：US20130177501A1

  公开（公告）日：2013-07-11

  The present invention provides a method useful in the diagnosis and/or monitoring of mood disorders wherein there is an abnormal expression of PBR. The method of the invention is useful in the differential diagnosis of said mood disorders and other conditions where there is no abnormal expression of PBR but where the symptoms may be similar to those of said mood disorder.

  本发明提供了一种在诊断和/或监测情绪障碍方面有用的方法，其中存在PBR异常表达。本发明的方法对于区分所述情绪障碍和其他情况有用，其他情况中PBR表达正常但症状可能类似于所述情绪障碍的情况。
• In vivo imaging method of mood disorders
  申请人：Jones Paul Alexander

  公开号：US09168317B2

  公开（公告）日：2015-10-27

  The present invention provides a method useful in the diagnosis and/or monitoring of mood disorders wherein there is an abnormal expression of PBR. The method of the invention is useful in the differential diagnosis of said mood disorders and other conditions where there is no abnormal expression of PBR but where the symptoms may be similar to those of said mood disorder.

  本发明提供了一种在诊断和/或监测情绪障碍方面有用的方法，其中存在PBR异常表达。该发明的方法对于区分所述情绪障碍和其他情况有用，其他情况中PBR表达正常但症状可能类似于所述情绪障碍。
• IN VIVO IMAGING METHOD FOR CANCER
  申请人：Jones Paul Alexander

  公开号：US20130183240A1

  公开（公告）日：2013-07-18

  The present invention provides a method useful in the diagnosis and monitoring of cancer wherein there is an abnormal expression of PBR. The method of the invention is particularly useful in evaluating the severity of the cancer, e.g. PBR expression correlates with cell proliferation rates, metastatic potential, tumour aggressiveness, malignancy progression. The method of the invention can therefore be applied in the determination of likely disease progression and in making an associated prognosis. Furthermore, the method of the invention can find use in determining the likely success of certain therapeutic approaches, or in the evaluation of the efficacy of certain proposed new treatments.

  本发明提供了一种在癌症诊断和监测中有用的方法，其中PBR的表达异常。本发明的方法特别适用于评估癌症的严重程度，例如PBR的表达与细胞增殖率、转移潜力、肿瘤侵袭性、恶性进展相关。因此，本发明的方法可用于确定可能的疾病进展，并作出相关预后。此外，本发明的方法可用于确定某些治疗方法的可能成功率，或评估某些拟议新治疗方法的疗效。
• Tricyclic indole derivatives as PBR ligands
  申请人：GE Healthcare Limited

  公开号：EP2411362B1

  公开（公告）日：2017-05-31