9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine
• 英文别名: [18F]FHPG；9-[(1-[18F]fluoro-3-hydroxy-2-propoxy)methyl]guanine；2-amino-9-[(1-(18F)fluoranyl-3-hydroxypropan-2-yl)oxymethyl]-1H-purin-6-one
• 化学式: C₉H₁₂FN₅O₃
• 分子量: 256.226
• InChiKey: NNQXQVNIWUIGQN-LMANFOLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  115
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  更昔洛韦 在 吡啶 、 4-二甲氨基吡啶 、 potassium [¹⁸F]fluoride 、 三乙胺 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 2.92h， 生成 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine
  参考文献：
  名称：

  有效合成9-（4- [ 18 F]氟-3-羟基甲基丁基）鸟嘌呤（[ 18 F] FHBG）和9-[（3- [ 18 F]氟-1-羟基-2-丙氧基）甲基]鸟嘌呤（[ 18 F] FHPG）

  摘要：

  这项工作报道了[ 18 F] FHBG和[ 18 F] FHPG的新的高放射化学收率合成，这是目前正用于监测使用正电子发射断层扫描（PET）进行基因治疗的最流行的成像剂。发现通常使用亲核的18 F-氟化反应来保护制备[ 18 F] FHBG和[ 18 F] FHPG的前体中的敏感位点，对于合成方法的良好放射化学收率，可靠性和可重复性至关重要。最初的方法是在当前使用的单甲氧基三苯甲基保护的喷昔洛韦甲苯磺酸酯衍生物9的鸟嘌呤部分的O 6氧处进行保护。与氨基甲酰基一起进行。随后，两者的充分保护ö 6 -氧和Ñ 2 -氮在单甲氧保护喷昔洛韦和更昔洛韦甲苯磺酸酯类似物9和10，通过它们的反应与二-实现叔丁基二碳酸酯，这导致ö 6 -叔-丁基- ñ 2 -Boc单甲氧保护的喷昔洛韦甲苯磺酸酯18和ö 6 -叔丁基- ñ 2 -Boc单甲氧保护的更昔洛韦甲苯磺酸酯19， 分别。首先将新合成的氨基甲酰基和Boc保护的前体与与Kryptofix

  DOI：

  10.1016/j.jfluchem.2017.08.007

文献信息

• Preparation of tritium-labelled BIIL 260 of high specific radioactivity
  作者：V.P. Shevchenko、I.Yu. Nagaev、N.F. Myasoedov、A.B. Susan、R. Anderskewitz、F.W. Birke、K-H. Switek

  DOI：10.1002/jlcr.661

  日期：2003.3.15

  Various approaches to the synthesis of tritium-labelled BIIL 260 with high specific radioactivity were investigated. Attempts to incorporate tritium directly into BIIL 260 were made by solid-phase isotope exchange with tritium gas and by isotope exchange with tritiated water which yielded a final product with specific activities ranging from 2 to 7 Ci/mmol. However, the solid-phase and liquid-phase dehalogenations of an appropriate synthon fragment of BIIL 260 followed by its subsequent conversion to the final product via chemical synthesis yielded the desired tritium-labelled BIIL 260 with specific activities of 25 or 71 Ci/mmol, depending upon the precursors and methods used in the dehalogenation step. Copyright © 2002 John Wiley & Sons, Ltd.

  研究了多种合成高比放射性氚标记BIIL 260的方法。尝试通过与氚气的固相同位素交换以及与氚化水的同位素交换直接将氚引入BIIL 260，最终产品的比活性范围为2至7 Ci/mmol。然而，通过适当的BIIL 260合成片段进行固相和液相脱卤，然后通过化学合成将其转化为最终产品，得到的氚标记BIIL 260的比活性为25或71 Ci/mmol，这取决于在脱卤步骤中使用的前体和方法。版权 © 2002 John Wiley & Sons, Ltd.
• Syntheses of novel modified acyclic purine and pyrimidine nucleosides as potential substrates of herpes simplex virus type-1 thymidine kinase for monitoring gene expression
  作者：Michaela Grote、Steffi Noll、Bernhard Noll、Bernd Johannsen、Werner Kraus

  DOI：10.1139/v04-005

  日期：2004.4.1

  Suicide gene therapy with the herpes simplex virus type-1 thymidine kinase gene (HSV-1 tk) is considered to be a promising approach to the treatment of cancer. Making use of the lower specificity of the viral enzyme compared to human thymidine kinase, the therapy involves the administration of antiviral agents (e.g., ganciclovir) as prodrugs to induce enzymatic cell death in those cells that express the transferred gene. ¹⁸F-labelled derivatives have been described for monitoring location, duration, and magnitude of the viral kinase enzyme activity by positron emission tomography (PET). Since an optimal radiotracer has not been developed, novel substances were synthesized for monitoring gene expression. A group of 13 nucleoside analogues were synthesized, among them N¹-methyl-9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (5) and N¹-methyl-9-[(4-hydroxy)-3-hydroxymethylbutyl]guanine (7) as methyl analogues of ganciclovir and penciclovir and their related fluoro compounds (6, 8). Further novel derivatives include N⁶-methyl-9-[(1,3-dihydroxy-2-propoxy)methyl]-, N⁶-methyl-9-[(4-hydroxy)-3-hydroxymethylbutyl]adenine (9, 10), as well as the uracil derivatives 5-hydroxy-1-[(1,3-dihydroxy-2-propoxy)methyl]uracil (11), 6-methyl-1-[(1,3-dihydroxy-2-propoxy)-methyl]uracil (12), and its 3-fluoro-derivative (13).Key words: fluorinated nucleoside analogues, gene therapy, PET, thymidine kinase.

  自杀基因治疗利用单纯疱疹病毒1型胸腺嘧啶激酶基因（HSV-1 tk）被认为是治疗癌症的一种有前景的方法。该疗法利用病毒酶相对于人类胸腺嘧啶激酶的较低特异性，涉及向表达转移基因的细胞施加抗病毒药物（例如甘昔洛韦）作为前药，诱导这些细胞发生酶促细胞死亡。已经描述了¹⁸F标记的衍生物，用于通过正电子发射断层扫描（PET）监测病毒激酶酶活性的位置、持续时间和强度。由于尚未开发出最佳放射性示踪剂，因此合成了新颖的物质用于监测基因表达。合成了一组13个核苷类似物，其中包括N¹-甲基-9-[(1,3-二羟基-2-丙氧基)甲基]鸟苷（5）和N¹-甲基-9-[(4-羟基)-3-羟甲基丁基]鸟苷（7）作为甘昔洛韦和彭昔洛韦的甲基类似物及其相关的氟化合物（6，8）。进一步的新颖衍生物包括N⁶-甲基-9-[(1,3-二羟基-2-丙氧基)甲基]-，N⁶-甲基-9-[(4-羟基)-3-羟甲基丁基]腺嘌呤（9，10），以及尿嘧啶衍生物5-羟基-1-[(1,3-二羟基-2-丙氧基)甲基]尿嘧啶（11），6-甲基-1-[(1,3-二羟基-2-丙氧基)-甲基]尿嘧啶（12）及其3-氟衍生物（13）。关键词：氟化核苷类似物，基因治疗，PET，胸腺嘧啶激酶。
• An Improved Total Synthesis of PET HSV‐tk Gene Expression Imaging Agent 9‐[(3‐[¹⁸F]Fluoro‐1‐hydroxy‐2‐propoxy)methyl]guanine ([¹⁸F]FHPG)
  作者：Ji‐Quan Wang、Qi‐Huang Zheng、Xiangshu Fei、Xuan Liu、Thomas A. Gardner、Chinghai Kao、Sudhanshu P. Raikwar、Barbara E. Glick‐Wilson、Michael L. Sullivan、Bruce H. Mock、Gary D. Hutchins

  DOI：10.1081/scc-120028365

  日期：2004.12.31

  An improved total synthesis of [F-18]FHPG starting from 1,3-dibenzyloxy2-propanol and guanine has been developed. [F-18]FHPG was prepared by nucleophilic substitution of the appropriate precursor with [F-18]KF/ Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with a simplified Silica Sep-Pak solid-phase extraction (SPE) method in 10-15% radiochemical yield, and 70 min synthesis time from end of bombardment (EOB).
• Novel radiosynthesis of PET HSV-tk gene reporter probes [18F]FHPG and [18F]FHBG employing dual Sep-Pak SPE techniques
  作者：Ji-Quan Wang、Qi-Huang Zheng、Xiangshu Fei、Bruce H. Mock、Gary D. Hutchins

  DOI：10.1016/j.bmcl.2003.09.010

  日期：2003.11

  Positron emission tomography (PET) herpes simplex virus thymidine kinase (HSV-tk) gene reporter probes 9-[(3-[F-18]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([F-18]FHPG) and 9-(4-[F-18]fluoro-3-hydroxymethylbutyl)guanine ([F-18]FHBG) were prepared by nucleophilic substitution of the appropriate tosylated precursors with [F-18]KF/Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with a simplified dual Silica Sep-Pak solid-phase extraction (SPE) method in 15-30% radiochemical yield. (C) 2003 Elsevier Ltd. All rights reserved.
• Shiue; Hustinx; Zhuang, Journal of labelled compounds and radiopharmaceuticals, 1999, vol. 42, # SUPPL. 1, p. S13-S15
  作者：Shiue、Hustinx、Zhuang、Shiue、Alavi、Eck

  DOI：——

  日期：——