4-(([¹⁸F]-fluoro)phenyl)methanamine | 131865-54-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(([¹⁸F]-fluoro)phenyl)methanamine
• 英文别名: (4-[¹⁸F]Fluorophenyl)methanamine；4-<18F>fluorobenzylamine；4-[¹⁸F]fluorobenzylamine；[(18)F]4-fluorobenzylamine；4-[18F]fluorobenzylamine；(4-(18F)fluoranylphenyl)methanamine
• CAS: 131865-54-8
• 化学式: C₇H₈FN
• 分子量: 124.147
• InChiKey: IIFVWLUQBAIPMJ-COJKEBBMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  Methyl-1,6-dihydro-5-hydroxy-1-methyl-2-[1-methyl-1-[[(5-methyl-1,3,4-oxadiazole-2-yl)carbonyl]amino]ethyl]-6-oxo-pyrimidine-4-carboxylate 、 4-(([¹⁸F]-fluoro)phenyl)methanamine 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 0.17h， 生成 [(18)F]-Raltegravir
  参考文献：
  名称：

  Radiosynthesis of the HIV integrase inhibitor [18F]MK-0518 (Isentress)

  摘要：

  人类免疫缺陷病毒整合酶抑制剂[18F]MK-0518是通过三步一步放射合成法制备的。用[18F]氟化物对 4-氰基-N,N,N-三甲基三酸铵进行氟化，然后用甲基硫化硼络合物还原，制备出[18F]4-氟苄胺，放射化学收率为 50-68%。最后一步是将[18F]4-氟苄胺与酯类偶联剂偶联，根据起始的[18F]氟化物，经 HPLC 纯化后，未校正的总放射化学收率为 2%。在一次典型的运行中，总合成时间约为 90 分钟，得到 0.37-1.74 GBq (10-47 mCi) 的[18F]MK-0518。[18F]MK-0518的放射化学纯度>98%，比活度为243-1275 Ci/mmol（EOS，n=4）。通过[18F]4-氟苄胺，我们开发出了一种方便的三步一步放射性合成[18F]MK-0518的方法，为动物正电子发射断层扫描研究提供了足够数量的[18F]MK-0518。Copyright © 2010 John Wiley & Sons, Ltd. All Rights Reserved.

  DOI：

  10.1002/jlcr.1778
• 作为产物：
  描述：

  4-羟基苄胺 在 (cyclooctadienyl)(cyclopentadienyl)ruthenium chloride 、 2-氯-1,3-双(2,6-二异丙基苯基)-1H-氯化咪唑 、 氢氟酸 作用下， 以 乙醇 、 二甲基亚砜 、 乙腈 为溶剂， 反应 1.0h， 以30%的产率得到4-(([¹⁸F]-fluoro)phenyl)methanamine
  参考文献：
  名称：

  [EN] PROCESS FOR DEOXYFLUORINATION OF PHENOLS
  [FR] PROCÉDÉ DE DÉSOXYFLUORATION DE PHÉNOLS

  摘要：

  本发明涉及一种过渡金属催化的18F-脱氧氟化酚的过程。这种转化得益于容易获得的酚作为起始材料；能够容忍水分和大气环境，具有广泛的底物范围，并且可以转化为适合正电子发射断层扫描（PET）成像的剂量。

  公开号：

  WO2019025137A1

文献信息

• A general method for labeling oligodeoxynucleotides with 18F for in vivo PET imaging
  作者：Frédéric Dolle、Françoise Hinnen、Françoise Vaufrey、Bertrand Tavitian、Christian Crouzel

  DOI：10.1002/(sici)1099-1344(199704)39:4<319::aid-jlcr970>3.0.co;2-7

  日期：1997.4

  containing a single phosphorothioate monoester, and N-(4-radiohalobenzyl)-2-bromoacetamide. Yields of 40–45% (decay corrected) of pure [18F]N-(4-fluorobenzyl)-2-(ACCGATCCG3′-ps)-acetamide [18F]-(1) (around 30 mCi or 1.1 GBq) were obtained for the whole synthetic procedure (220 minutes) with respect to [18F]fluoride ion, with specific radioactivities as high as 3 Ci/μmole (111 TBq/μmol) calculated for End

  本文描述了一种合成携带正电子发射体 18F 的寡脱氧核苷酸 (ODN) 的原始通用方法。开发的标记策略简单、可靠，独立于骨架修饰和碱基序列。它应该对标记天然或修饰的 ODN 具有普遍适用性，前提是后者在其 3' 端带有硫代磷酸酯基团，并且它应该很容易转座到其他放射性卤素，如 76Br 或 123I。我们开发的方法使用最近制备规模的市售 3'-硫代磷酸寡脱氧核苷酸，基于寡脱氧核苷酸的有效偶联反应，含有单个硫代磷酸单酯和 N-（4-放射性卤代苄基）-2-溴乙酰胺。纯 [18F]N-(4-氟苄基)-2-(ACCGATCCG3'-ps)-乙酰胺 [18F]-(1)（约 30 mCi 或 1.1 GBq）的产率为 40-45%（衰减校正）对于 [18F] 氟离子的整个合成过程（220 分钟），针对轰击结束计算的特定放射性高达 3 Ci/μmole (111 TBq/μmol)（或 750 mCi/μmole
• Fluorine-18 labeling of peptide nucleic acids
  作者：Bertrand Kuhnast、Fr�d�ric Dolle、Bertrand Tavitian

  DOI：10.1002/jlcr.522

  日期：2002.1

  Peptide nucleic acids (PNAs) are a unique class of synthetic macromolecules, originally designed as ligands for the recognition of double stranded DNA. From a chemical point of view, the deoxyribose phosphate backbone of DNA is replaced by a pseudo-peptide N-(2-aminoethyl)glycyl backbone, while the nucleobases of DNA (adenine, guanine, cytosine and thymine) are retained. Due to the increasing interest in the labeling of peptide nucleic acids (PNAs) as potent diagnostic agents in nuclear medicine, we have used and adapted the reliable methodology developed for the fluorine-18 labeling of oligonucleotides and have now demonstrated that it is possible to label PNAs in sufficient quantity and with high specific radioactivity for PET studies in a time compatible with the half life of fluorine-18. Copyright © 2002 John Wiley & Sons, Ltd.

  肽核酸（PNAs）是一类独特的合成高分子，最初设计为双链DNA的配体。从化学角度来看，DNA的脱氧核糖磷酸主链被伪肽N-(2-氨基乙基)甘氨酸主链所取代，同时保留了DNA的核碱基（腺嘌呤、鸟嘌呤、胞嘧啶和胸腺嘧啶）。由于对肽核酸（PNAs）作为核医学中强效诊断试剂的标记兴趣日益增加，我们采用了为氟-18标记寡核苷酸所发展的可靠方法，并已证明在氟-18的半衰期兼容时间内，可以以足够数量和高比活度标记PNAs，用于PET研究。版权所有 © 2002 John Wiley & Sons, Ltd.
• Fluorine-18 labelling of PNAs functionalized at their pseudo-peptidic backbone for imaging studies with PET
  作者：B. Kuhnast、F. Hinnen、R. Hamzavi、R. Boisgard、B. Tavitian、P. E. Nielsen、F. Dollé

  DOI：10.1002/jlcr.895

  日期：2005.1

  Peptide nucleic acids (PNAs) form a unique class of synthetic macromolecules, originally designed as ligands for the recognition of double-stranded DNA, where the deoxyribose phosphate backbone of original DNA is replaced by a pseudo-peptide N-(2-aminoethyl)glycyl backbone, while retaining the nucleobases of DNA. We have previously developed an original method to label oligonucleotide-based macromolecules with the short-lived positron-emitter fluorine-18 (t1/2: 109.8 min) using the N-(4-[18F]fluorobenzyl)-2-bromoacetamide reagent. Using this method, we herein report the fluorine-18-labelling of 13 decameric PNAs (OLP_1-13), of the same sequence (CTCATACTCT), but presenting selected modification of the pseudo-peptidic backbone at two or three of the thymine residues (positions 2, 5 and 8). Structural characteristics of these backbone modifications include either an amino acid side chain (L-Lys, L-Glu, L-Leu and L-Arg) or a glycosyl moiety (mannose, galactose, fucose, N-Ac-galactosamine and N-Ac-glucosamine) attached via an appropriate spacer. N-(4-[18F]fluorobenzyl)-2-bromoacetamide was synthesized in three radiochemical steps from 4-cyano-N,N,N-trimethylanilinium trifluoromethanesulfonate and HPLC-purified in 85–90 min (typical production: 3.7–4.8 GBq starting from a batch of 29.6–31.4 GBq of [18F]fluoride). Conjugation of the fluorine-18-labelled bromoacetamide reagent with the PNAs was performed in a mixture of acetonitrile and HEPES buffer (0.1 M, pH 7.9) for 10 min at 60°C and gave the corresponding pure labelled conjugated PNAs ([18F]c-OLP_1-13) after RP-HPLC purification. The whole synthetic procedure, including the preparation of the fluorine-18-labelled reagent, provides up to 0.9 GBq (25 mCi) of HPLC-purified [18F]c-OLP_1-13 in 160 min with a specific radioactivity of 45–65 GBq/µmol (1.2–1.7 Ci/µmol) at the end of synthesis starting from 29.6 to 31.4 GBq (800–850 mCi) of [18F]fluoride. Copyright © 2004 John Wiley & Sons, Ltd.

  肽核酸（PNA）形成了一类独特的合成大分子，最初设计为识别双链DNA的配体，其中原DNA的脱氧核糖磷酸骨架被伪肽N-(2-氨基乙基)甘氨酸骨架所替代，同时保留DNA的核苷酸。我们之前开发了一种新方法，利用N-(4-[18F]氟苄基)-2-溴乙酰胺试剂对基于寡核苷酸的大分子进行短寿命正电子发射体氟-18的标记（半衰期：109.8分钟）。在此方法的基础上，我们报告了对13种十聚肽PNA（OLP_1-13）的氟-18标记，这些PNA具有相同的序列（CTCATACTCT），但在两个或三个胸腺嘧啶残基（位置2、5和8）上进行了选择性修饰。骨架修饰的结构特征包括通过适当的间隔连接的氨基酸侧链（L-赖氨酸、L-谷氨酸、L-亮氨酸和L-精氨酸）或糖苷基团（甘露糖、半乳糖、岩藻糖、N-乙酰半乳糖胺和N-乙酰葡萄糖胺）。N-(4-[18F]氟苄基)-2-溴乙酰胺通过三步放射化学反应从4-氰基-N,N,N-三甲基苯胺三氟甲磺酸酯合成，并在85-90分钟内通过HPLC纯化（典型产量：从29.6-31.4 GBq的[18F]氟化物起始，产生3.7-4.8 GBq）。氟-18标记的溴乙酰胺试剂与PNA的结合是在60°C下的乙腈和HEPES缓冲液（0.1 M，pH 7.9）混合物中进行的，反应时间为10分钟，经过RP-HPLC纯化后得到相应的纯标记化合物PNA（[18F]c-OLP_1-13）。整个合成过程，包括氟-18标记试剂的制备，能在160分钟内提供高达0.9 GBq（25 mCi）的HPLC纯化的[18F]c-OLP_1-13，具体放射活度为45-65 GBq/µmol（1.2-1.7 Ci/µmol），起始于29.6至31.4 GBq（800-850 mCi）的[18F]氟化物。著作权 © 2004 John Wiley & Sons, Ltd.
• Design, Synthesis, and Evaluation of an¹⁸F-Labeled Radiotracer Based on Celecoxib-NBD for Positron Emission Tomography (PET) Imaging of Cyclooxygenase-2 (COX-2)
  作者：Jatinder Kaur、Ole Tietz、Atul Bhardwaj、Alison Marshall、Jenilee Way、Melinda Wuest、Frank Wuest

  DOI：10.1002/cmdc.201500287

  日期：2015.10

  cyclooxygenase‐2 (COX‐2) inhibitors was designed and synthesized based on the previously reported fluorescent COX‐2 imaging agent celecoxib–NBD (3; NBD=7‐nitrobenzofurazan). In vitro COX‐1/COX‐2 inhibitory data show that N‐(4‐fluorobenzyl)‐4‐(5‐p‐tolyl‐3‐trifluoromethylpyrazol‐1‐yl)benzenesulfonamide (5; IC50=0.36 μM, SI>277) and N‐fluoromethyl‐4‐(5‐p‐tolyl‐3‐trifluoromethylpyrazol‐1‐yl)benzenesulfonamide (6;

  根据先前报道的荧光COX-2成像剂celecoxib-NBD（3； NBD = 7-硝基-硝基苯并呋喃），设计和合成了一系列新型的含氟环氧合酶-2（COX-2）抑制剂。体外COX-1 / COX-2抑制的数据显示，ñ - （4-氟苄基）-4-（5- p -甲苯基-3-三氟甲基吡唑-1-基）苯磺酰胺（5 ; IC 50 = 0.36μ中号，SI > 277）和ñ -氟-4-（5- p -甲苯基-3-三氟甲基吡唑-1-基）苯磺酰胺（6 ; IC 50 = 0.24μ中号，SI> 416）是有效的和选择性COX-2抑制剂。化合物5选择使用短寿命的正电子发射器Fluor-18（18 F）进行放射性标记，并作为正电子发射断层扫描（PET）成像剂进行评估。使用人类结直肠癌模型HCA-7在体外和体内对Radiotracer [ 18 F] 5进行了分析。尽管放射性示踪剂对表达COX-2的HCA-7细胞的
• Synthesis of three 18F-labelled cyclooxygenase-2 (COX-2) inhibitors based on a pyrimidine scaffold
  作者：Ole Tietz、Sai Kiran Sharma、Jatinder Kaur、Jenilee Way、Alison Marshall、Melinda Wuest、Frank Wuest

  DOI：10.1039/c3ob41935e

  日期：——

  Cyclooxygenase (COX) is the key enzyme within the complex conversion of arachidonic acid into prostaglandins (PGs). Inhibitors of this enzyme represent a particularly promising class of compounds for chemoprevention and cancer therapy. The experimental data on the involvement of COX isoform COX-2 in tumour development and progression, as well as the observed overexpression of COX-2 in a variety of human cancers provide the rationale for targeting COX-2 for molecular imaging and therapy of cancer. A series of trifluoromethyl-substituted pyrimidines was prepared as a novel class of selective COX-2 inhibitors, based on the lead structure 1a. All compounds were tested in cyclooxygenase (COX) assays in vitro to determine COX-1 and COX-2 inhibitory potency and selectivity. Molecular docking studies using the catalytic site of COX-1 and COX-2, respectively, provided complementary theoretical support for the obtained experimental biological structure–activity relationship data of three highly potent and selective fluorobenzyl-containing COX-2 inhibitors. Selected fluorobenzyl-substituted pyrimidine derivatives were further developed as 18F-labelled radiotracers ([18F]1a, [18F]2a, [18F]3a). Radiotracers [18F]1a and [18F]2a were radiolabelled using 4-[18F]fluorobenzylamine ([18F]FBA) as a building block. Radiotracer [18F]3a was radiofluorinated directly using a nucleophilic aromatic substitution reaction with no-carrier-added (n.c.a.) [18F]fluoride on an iodylaryl compound as a labelling precursor.

  环氧合酶（COX）是将花生四烯酸转化为前列腺素（PGs）的复杂过程中的关键酶。这种酶的抑制剂是一类特别有前景的化合物，适用于化学预防和癌症疗法。COX亚型COX-2参与肿瘤发生和发展的实验数据，以及在人类多种癌症中观察到的COX-2过表达，为靶向COX-2进行癌症的分子成像和治疗提供了理论依据。以先导结构1a为基础，合成了一系列三氟甲基取代的嘧啶化合物，作为新型选择性COX-2抑制剂。所有化合物均在体外的环氧合酶（COX）测定中进行了测试，以确定COX-1和COX-2的抑制效力和选择性。使用COX-1和COX-2的催化位点进行的分子对接研究，为获得的三种高效且选择性强的含氟苄基COX-2抑制剂的实验生物结构–活性关系数据提供了补充的理论支持。选择的氟苄基取代嘧啶衍生物进一步开发为18F标记的放射示踪剂（[18F]1a, [18F]2a, [18F]3a）。放射示踪剂[18F]1a和[18F]2a使用4-[18F]氟苄胺（[18F]FBA）作为构建块进行放射标记。放射示踪剂[18F]3a则通过与无载体添加（n.c.a.）的[18F]氟化物在碘芳基化合物上进行亲核芳香取代反应直接进行放射氟化。