9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine | 206067-82-5

• 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-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine
• 英文别名: [18F]FHBG；9-(4-(18F)Fluoro-3-(hydroxymethyl)butyl)guanine；2-amino-9-[3-((18F)fluoranylmethyl)-4-hydroxybutyl]-1H-purin-6-one
• CAS: 206067-82-5
• 化学式: C₁₀H₁₄FN₅O₂
• 分子量: 254.253
• InChiKey: CEIVUGLBKBWVAE-KXMUYVCJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N²-(p-anisyldiphenylmethyl)-9-[(4-hydroxy)-3-p-anisyldiphenylmethoxymethylbutyl]guanine 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-(4-[18F]fluoro-3-hydroxymethylbutyl)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

• 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。
• 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.
• Zheng, Q.-H.; Wang, J.-Q.; Liu, X., Journal of labelled compounds and radiopharmaceuticals, 2003, vol. 46, p. S112 - S112
  作者：Zheng, Q.-H.、Wang, J.-Q.、Liu, X.、Fei, X.、Mock, B. H.、Glick-Wilson, B. E.、Sullivan, M. L.、Raikwar, S. P.、Gardner, T. A.、Kao, C.、Hutchins, G. D.

  DOI：——

  日期：——
• An Improved Total Synthesis of PET HSV‐tk Gene Reporter Probe 9‐(4‐[¹⁸F]Fluoro‐3‐hydroxymethylbutyl)guanine ([¹⁸F]FHBG)
  作者：Qi‐Huang Zheng、Ji‐Quan Wang、Xuan Liu、Xiangshu Fei、Bruce H. Mock、Barbara E. Glick‐Wilson、Michael L. Sullivan、Sudhanshu P. Raikwar、Thomas A. Gardner、Chinghai Kao、Gary D. Hutchins

  DOI：10.1081/scc-120027717

  日期：2004.12.31

  An improved total synthesis of [F-18]FHBG starting from triethyl-1,1,2-ethanetricarboxylate and 2-amino-6-chloropurine is reported. [F-18]FHBG 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 20-25% radiochemical yield.
• Efficient synthesis of 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) and 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([18F]FHPG)
  作者：Jie Liu、Jorge R. Barrio、Nagichettiar Satyamurthy

  DOI：10.1016/j.jfluchem.2017.08.007

  日期：2017.9

  A new, high radiochemical yield synthesis of [18F]FHBG and [18F]FHPG, the most popular imaging agents currently in use for monitoring gene therapy using positron emission tomography (PET), is reported in this work. Protection of sensitive sites in the precursors generally utilized for the preparation of [18F]FHBG and [18F]FHPG using the nucleophilic 18F-fluorination reaction was found to be critical

  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