2-fluoro-3-pent-4-yn-1-yloxypyridine | 1161009-63-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-fluoro-3-pent-4-yn-1-yloxypyridine
• 英文别名: 2-Fluoro-3-(pent-4-yn-1-yloxy)pyridine；2-fluoro-3-pent-4-ynoxypyridine
• CAS: 1161009-63-7
• 化学式: C₁₀H₁₀FNO
• mdl: MFCD20275190
• 分子量: 179.194
• InChiKey: SNLAKILJYDTTJK-UHFFFAOYSA-N

物化性质

• 沸点：
  279.2±30.0 °C(Predicted)
• 密度：
  1.115±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-fluoro-3-pent-4-yn-1-yloxypyridine 、 2-butyl-4-chloro-5-(azidomethyl)-1-[[2'-[(triphenylmethyl)tetrazole-5-yl]biphenyl-4-yl]methyl]imidazole 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  Synthesis and evaluation of the novel 2-[18F]fluoro-3-propoxy-triazole-pyridine-substituted losartan for imaging AT1 receptors

  摘要：

  The 2-[F-18]fluoro-3-pent-4-yn-1-yloxypyridine ([F-18]FPyKYNE) analog of the potent non-peptide angiotensin II type 1 receptor (AT(1)R) blocker losartan was produced via click chemistry linking [F-18]FPyKYNE to azide-modified tetrazole-protected losartan followed by TFA deprotection. Preliminary small animal imaging with positron emission tomography (PET) in rats displayed high uptake in the kidneys with good contrast to surrounding tissue. Rat metabolism displayed the presence of 23% unchanged tracer in plasma at 30 min. Upon co-administration with AT(1)R blocker candesartan (2.5, 5 and 10 mg/kg), a dose-dependent reduction (47-65%) in tracer uptake was observed in the kidney, while no difference was observed following AT(2)R blocker PD123,319 (5 mg/kg), indicating binding selectivity for AT(1)R over AT(2)R and potential for imaging AT(1)R using PET. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.06.011
• 作为产物：
  描述：

  3-羟基-2-硝基吡啶 在 potassium fluoride 、 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 、 sodium iodide 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 2-fluoro-3-pent-4-yn-1-yloxypyridine
  参考文献：
  名称：

  Synthesis and evaluation of the novel 2-[18F]fluoro-3-propoxy-triazole-pyridine-substituted losartan for imaging AT1 receptors

  摘要：

  The 2-[F-18]fluoro-3-pent-4-yn-1-yloxypyridine ([F-18]FPyKYNE) analog of the potent non-peptide angiotensin II type 1 receptor (AT(1)R) blocker losartan was produced via click chemistry linking [F-18]FPyKYNE to azide-modified tetrazole-protected losartan followed by TFA deprotection. Preliminary small animal imaging with positron emission tomography (PET) in rats displayed high uptake in the kidneys with good contrast to surrounding tissue. Rat metabolism displayed the presence of 23% unchanged tracer in plasma at 30 min. Upon co-administration with AT(1)R blocker candesartan (2.5, 5 and 10 mg/kg), a dose-dependent reduction (47-65%) in tracer uptake was observed in the kidney, while no difference was observed following AT(2)R blocker PD123,319 (5 mg/kg), indicating binding selectivity for AT(1)R over AT(2)R and potential for imaging AT(1)R using PET. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.06.011

文献信息

• [¹⁸F]FPyKYNE, a fluoropyridine-based alkyne reagent designed for the fluorine-18 labelling of macromolecules using click chemistry
  作者：Bertrand Kuhnast、Françoise Hinnen、Bertrand Tavitian、Frédéric Dollé

  DOI：10.1002/jlcr.1533

  日期：2008.8

  FPyKYNE (2-fluoro-3-pent-4-yn-1-yloxypyridine) is a novel fluoropyridine-based structure, designed for the fluorine-18 labelling of macromolecules using copper-catalysed Huisgen 1,3-dipolar cycloaddition (click chemistry). FPyKYNE (non-labelled as reference), as well as the 2-bromo, 2-nitro and 2-trimethylammonium analogues (as precursors for labelling with fluorine-18), was synthesized in 44, 95, 60 and 41%, respectively, from commercially available 5-chloropent-1-yne and the appropriate 2-substituted-3-hydroxypyridines. [18F]FPyKYNE was synthesized in one single radiochemical step by reaction of no-carrier-added K[18F]F-Kryptofix®222 (DMSO, 165°C, 3–5 min) followed by C-18 SepPak cartridge pre-purification and finally semi-preparative HPLC purification on a Hewlett Packard SiO2 Zorbax® Rx-SIL. Using the 2-nitropyridine or the pyridin-2-yltrimethylammonium trifluoromethanesulphonate precursor for labelling (30 and 10 µmol, respectively), incorporation yields up to 90% were observed and 7.0–8.9 GBq (190–240 mCi) of [18F]FPyKYNE ([18F]-1) could be isolated within 60–70 min (HPLC purification included), starting from a 37.0 GBq (1.0 Ci) [18F]fluoride batch (overall decay-corrected and isolated yields: 30–35%). Copyright © 2008 John Wiley & Sons, Ltd.

  FPyKYNE（2-氟-3-戊-4-炔-1-氧基吡啶）是一种新型的氟吡啶基结构，旨在通过铜催化的Huisgen 1,3-偶极环加成（点击化学）对大分子进行氟-18标记。FPyKYNE（未标记作为参考）以及2-溴、2-硝基和2-三甲基铵类似物（作为氟-18标记的前体）分别以44%、95%、60%和41%的产率从商业可得的5-氯戊-1-炔和适当的2-取代-3-羟基吡啶合成。[18F]FPyKYNE通过与无载体的K[18F]F-Kryptofix®222反应（DMSO，165°C，3–5分钟）在一个放射化学步骤中合成，随后进行C-18 SepPak柱的预纯化，最后在Hewlett Packard SiO2 Zorbax® Rx-SIL上进行半制备HPLC纯化。使用2-硝基吡啶或吡啶-2-基三甲基铵三氟甲磺酸盐前体进行标记（分别为30和10微摩尔），观察到高达90%的掺入产率，并且可以在60–70分钟内分离出7.0–8.9 GBq（190–240 mCi）的[18F]FPyKYNE（[18F]-1），起始于37.0 GBq（1.0 Ci）的[18F]氟化物批次（整体衰减校正和分离产率：30–35%）。版权所有 © 2008 John Wiley & Sons, Ltd.
• A fast, simple, and reproducible automated synthesis of [18F]FPyKYNE-c(RGDyK) for αvβ3 receptor positron emission tomography imaging
  作者：Ana C. Valdivia、Miriam Estrada、Tayebeh Hadizad、Duncan J. Stewart、Rob S. Beanlands、Jean N. DaSilva

  DOI：10.1002/jlcr.1948

  日期：2012.2

  [18 F]FPyKYNE-c(RGDyK) was successfully synthesized by the Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition of alkynes to azides using [18 F]FPyKYNE as a prosthetic group in an overall radiochemical yield of 12%–18% (decay-corrected) and >99.5% chemical and radiochemical purities in 125 min including quality control. This simple, fully automated two-step, two-reactor approach consists of a quick and convenient purification of the prosthetic group using silica gel cartridges and its subsequent use for the labeling of the azido-c(RGDyK) peptide via click chemistry.

  [18F]FPyKYNE-c(RGDyK)由Cu(I)催化Huisgen 1,3-双极性环加成反应成功合成，其中炔烃以[18F]FPyKYNE作为辅助基团与叠氮化物反应，总放射化学收率为12%–18%（衰减校正），化学纯度和放射化学纯度均大于99.5%，整个过程（包括质量控制）耗时125分钟。这种简单、全自动的两步两反应器方法包括使用硅胶柱快速、方便地纯化辅助基团，以及随后通过点击化学将叠氮化物-c(RGDyK)肽进行标记。
• Synthesis and evaluation of the novel 2-[18F]fluoro-3-propoxy-triazole-pyridine-substituted losartan for imaging AT1 receptors
  作者：Natasha Arksey、Tayebeh Hadizad、Basma Ismail、Maryam Hachem、Ana C. Valdivia、Rob S. Beanlands、Robert A. deKemp、Jean N. DaSilva

  DOI：10.1016/j.bmc.2014.06.011

  日期：2014.8

  The 2-[F-18]fluoro-3-pent-4-yn-1-yloxypyridine ([F-18]FPyKYNE) analog of the potent non-peptide angiotensin II type 1 receptor (AT(1)R) blocker losartan was produced via click chemistry linking [F-18]FPyKYNE to azide-modified tetrazole-protected losartan followed by TFA deprotection. Preliminary small animal imaging with positron emission tomography (PET) in rats displayed high uptake in the kidneys with good contrast to surrounding tissue. Rat metabolism displayed the presence of 23% unchanged tracer in plasma at 30 min. Upon co-administration with AT(1)R blocker candesartan (2.5, 5 and 10 mg/kg), a dose-dependent reduction (47-65%) in tracer uptake was observed in the kidney, while no difference was observed following AT(2)R blocker PD123,319 (5 mg/kg), indicating binding selectivity for AT(1)R over AT(2)R and potential for imaging AT(1)R using PET. (C) 2014 Elsevier Ltd. All rights reserved.