(R)-(+)-methyl 1-[1-(4-fluorophenyl)ethyl]-1H-imidazole-5-carboxylate | 1423566-94-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (R)-(+)-methyl 1-[1-(4-fluorophenyl)ethyl]-1H-imidazole-5-carboxylate
• 英文别名: methyl 3-[(1R)-1-(4-fluorophenyl)ethyl]imidazole-4-carboxylate
• CAS: 1423566-94-2
• 化学式: C₁₃H₁₃FN₂O₂
• 分子量: 248.257
• InChiKey: GGWGCYVYFWXYJK-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-(+)-methyl 1-[1-(4-fluorophenyl)ethyl]-1H-imidazole-5-carboxylate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 17.0h， 生成 3-[(1R)-1-(4-fluorophenyl)ethyl]imidazole-4-carboxylic acid
  参考文献：
  名称：

  Development of [18F]FAMTO: A novel fluorine-18 labelled positron emission tomography (PET) radiotracer for imaging CYP11B1 and CYP11B2 enzymes in adrenal glands

  摘要：

  Introduction: Primary aldosteronism accounts for 6-15% of hypertension cases, the single biggest contributor to global morbidity and mortality. Whilst similar to 50% of these patients have unilateral aldosterone-producing adenomas, only a minority of these have curative surgery as the current diagnosis of unilateral disease is poor. Carbon-11 radiolabelled metomidate ([C-11]MTO) is a positron emission tomography (PET) radiotracer able to selectively identify CYP11B1/2 expressing adrenocortical lesions of the adrenal gland. However, the use of [C-11]MTO is limited to PET centres equipped with on-site cyclotrons due to its short half-life of 20.4 min. Radiolabelling a fluorometomidate derivative with fluorine-18 (radioactive half life 109.8 min) in the para-aromatic position ([F-18]FAMTO) has the potential to overcome this disadvantage and allow it to be transported to noncyclotron-based imaging centres.Methods: Two strategies for the one-step radio-synthesis of [F-18]FAMTO were developed. [F-18]FAMTO was obtained via radiofluorination via use of sulfonium salt (1) and boronic ester (2) precursors. [ 18 F]FAMTO was evaluated in vitro by autoradiography of pig adrenal tissues and in vivo by determining its biodistribution in rodents. Rat plasma and urine were analysed to determine [F-18]FAMTO metabolites.Results: [F-18]FAMTO is obtained from sulfonium salt (1) and boronic ester (2) precursors in 7% and 32% nonisolated radiochemical yield (RCY), respectively. Formulated [F-18]FAMTO was obtained with >99% radiochemical and enantiomeric purity with a synthesis time of 140 min from the trapping of [F-18]fluoride ion on an anionexchange resin (QMA cartridge). In vitro autoradiography of [F-18]FAMTO demonstrated exquisite specific binding in CYP11B-rich pig adrenal glands. In vivo [F-18]FAMTO rapidly accumulates in adrenal glands. Liver uptake was about 34% of that in the adrenals and all other organs were <12% of the adrenal uptake at 60 min post-injection. Metabolite analysis showed 13% unchanged [F-18]FAMTO in blood at 10 min post-administration and rapid urinary excretion. In vitro assays in human blood showed a free fraction of 37.5%.Conclusions: [F-18]FAMTO, a new F-18-labelled analogue of metomidate, was successfully synthesised. In vitro and in vivo characterization demonstrated high selectivity towards aldosterone-producing enzymes (CYP11B1 and CYP11B2), supporting the potential of this radiotracer for human investigation. (C) 2018 The Authors. Published by Elsevier Inc.

  DOI：

  10.1016/j.nucmedbio.2018.11.002
• 作为产物：
  描述：

  (S)-1-(4-氟苯基)乙醇 、 咪唑-4-甲酸甲酯 在 偶氮二甲酸二叔丁酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 生成 (R)-(+)-methyl 1-[1-(4-fluorophenyl)ethyl]-1H-imidazole-5-carboxylate
  参考文献：
  名称：

  Development of [18F]FAMTO: A novel fluorine-18 labelled positron emission tomography (PET) radiotracer for imaging CYP11B1 and CYP11B2 enzymes in adrenal glands

  摘要：

  Introduction: Primary aldosteronism accounts for 6-15% of hypertension cases, the single biggest contributor to global morbidity and mortality. Whilst similar to 50% of these patients have unilateral aldosterone-producing adenomas, only a minority of these have curative surgery as the current diagnosis of unilateral disease is poor. Carbon-11 radiolabelled metomidate ([C-11]MTO) is a positron emission tomography (PET) radiotracer able to selectively identify CYP11B1/2 expressing adrenocortical lesions of the adrenal gland. However, the use of [C-11]MTO is limited to PET centres equipped with on-site cyclotrons due to its short half-life of 20.4 min. Radiolabelling a fluorometomidate derivative with fluorine-18 (radioactive half life 109.8 min) in the para-aromatic position ([F-18]FAMTO) has the potential to overcome this disadvantage and allow it to be transported to noncyclotron-based imaging centres.Methods: Two strategies for the one-step radio-synthesis of [F-18]FAMTO were developed. [F-18]FAMTO was obtained via radiofluorination via use of sulfonium salt (1) and boronic ester (2) precursors. [ 18 F]FAMTO was evaluated in vitro by autoradiography of pig adrenal tissues and in vivo by determining its biodistribution in rodents. Rat plasma and urine were analysed to determine [F-18]FAMTO metabolites.Results: [F-18]FAMTO is obtained from sulfonium salt (1) and boronic ester (2) precursors in 7% and 32% nonisolated radiochemical yield (RCY), respectively. Formulated [F-18]FAMTO was obtained with >99% radiochemical and enantiomeric purity with a synthesis time of 140 min from the trapping of [F-18]fluoride ion on an anionexchange resin (QMA cartridge). In vitro autoradiography of [F-18]FAMTO demonstrated exquisite specific binding in CYP11B-rich pig adrenal glands. In vivo [F-18]FAMTO rapidly accumulates in adrenal glands. Liver uptake was about 34% of that in the adrenals and all other organs were <12% of the adrenal uptake at 60 min post-injection. Metabolite analysis showed 13% unchanged [F-18]FAMTO in blood at 10 min post-administration and rapid urinary excretion. In vitro assays in human blood showed a free fraction of 37.5%.Conclusions: [F-18]FAMTO, a new F-18-labelled analogue of metomidate, was successfully synthesised. In vitro and in vivo characterization demonstrated high selectivity towards aldosterone-producing enzymes (CYP11B1 and CYP11B2), supporting the potential of this radiotracer for human investigation. (C) 2018 The Authors. Published by Elsevier Inc.

  DOI：

  10.1016/j.nucmedbio.2018.11.002

文献信息

• Development of [18F]FAMTO: A novel fluorine-18 labelled positron emission tomography (PET) radiotracer for imaging CYP11B1 and CYP11B2 enzymes in adrenal glands
  作者：Salvatore Bongarzone、Filippo Basagni、Teresa Sementa、Nisha Singh、Caleb Gakpetor、Vincent Faugeras、Jayanta Bordoloi、Antony D. Gee

  DOI：10.1016/j.nucmedbio.2018.11.002

  日期：2019.1

  Introduction: Primary aldosteronism accounts for 6-15% of hypertension cases, the single biggest contributor to global morbidity and mortality. Whilst similar to 50% of these patients have unilateral aldosterone-producing adenomas, only a minority of these have curative surgery as the current diagnosis of unilateral disease is poor. Carbon-11 radiolabelled metomidate ([C-11]MTO) is a positron emission tomography (PET) radiotracer able to selectively identify CYP11B1/2 expressing adrenocortical lesions of the adrenal gland. However, the use of [C-11]MTO is limited to PET centres equipped with on-site cyclotrons due to its short half-life of 20.4 min. Radiolabelling a fluorometomidate derivative with fluorine-18 (radioactive half life 109.8 min) in the para-aromatic position ([F-18]FAMTO) has the potential to overcome this disadvantage and allow it to be transported to noncyclotron-based imaging centres.Methods: Two strategies for the one-step radio-synthesis of [F-18]FAMTO were developed. [F-18]FAMTO was obtained via radiofluorination via use of sulfonium salt (1) and boronic ester (2) precursors. [ 18 F]FAMTO was evaluated in vitro by autoradiography of pig adrenal tissues and in vivo by determining its biodistribution in rodents. Rat plasma and urine were analysed to determine [F-18]FAMTO metabolites.Results: [F-18]FAMTO is obtained from sulfonium salt (1) and boronic ester (2) precursors in 7% and 32% nonisolated radiochemical yield (RCY), respectively. Formulated [F-18]FAMTO was obtained with >99% radiochemical and enantiomeric purity with a synthesis time of 140 min from the trapping of [F-18]fluoride ion on an anionexchange resin (QMA cartridge). In vitro autoradiography of [F-18]FAMTO demonstrated exquisite specific binding in CYP11B-rich pig adrenal glands. In vivo [F-18]FAMTO rapidly accumulates in adrenal glands. Liver uptake was about 34% of that in the adrenals and all other organs were <12% of the adrenal uptake at 60 min post-injection. Metabolite analysis showed 13% unchanged [F-18]FAMTO in blood at 10 min post-administration and rapid urinary excretion. In vitro assays in human blood showed a free fraction of 37.5%.Conclusions: [F-18]FAMTO, a new F-18-labelled analogue of metomidate, was successfully synthesised. In vitro and in vivo characterization demonstrated high selectivity towards aldosterone-producing enzymes (CYP11B1 and CYP11B2), supporting the potential of this radiotracer for human investigation. (C) 2018 The Authors. Published by Elsevier Inc.