4-(2-fluoroethyl)aniline | 327985-14-8

• 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-(2-fluoroethyl)aniline
• 英文别名: 1-Fluoro-2-(4-aminophenyl)ethane
• CAS: 327985-14-8
• 化学式: C₈H₁₀FN
• 分子量: 139.173
• InChiKey: PYFJEDYCQWECQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  4-(2-fluoroethyl)aniline 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.08h， 生成
  参考文献：
  名称：

  Design and synthesis of a fluorinated quinazoline-based type-II Trk inhibitor as a scaffold for PET radiotracer development

  摘要：

  NTRK1/2/3 fusions have recently been characterized as low incidence oncogenic alterations across various tumor histologies. Tyrosine kinase inhibitors (TKIs) of the tropomyosin receptor kinase family TrkA/B/C (encoded by NTRK1/2/3) are showing promises in the clinic for the treatment of cancer patients whose diseases harbor NTRK tumor drivers. We describe herein the development of [F-18] QMICF ([F-18]-(R)-9), a quinazoline-based type-II pan-Trk radiotracer with nanomolar potencies for TrkA/B/C (IC50 = 85-650 nM) and relevant TrkA fusions including TrkA-TPM3 (IC50 = 162 nM). Starting from a racemic FLT3 (fms like tyrosine kinase 3) inhibitor lead with off-target TrkA activity ((+/-)-6), we developed and synthesized the fluorinated derivative (R)-9 in three steps and 40% overall chemical yield. Compound (R)-9 displays a favorable selectivity profile on a diverse set of kinases including FLT3 (>37-fold selectivity for TrkB/C). The mesylate precursor 16 required for the radiosynthesis of [F-18] QMICF was obtained in six steps and 36% overall yield. The results presented herein support the further exploration of [F-18] QMICF for imaging of Trk fusions in vivo. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.04.064
• 作为产物：
  描述：

  4-氨基苯乙醇 在 二乙胺基三氟化硫 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 27.5h， 生成 4-(2-fluoroethyl)aniline
  参考文献：
  名称：

  开发亚纳摩尔级放射性氟化（2-吡咯烷-1-基）咪唑并[1,2 - b ]哒嗪pan-Trk抑制剂作为PET成像探针†

  摘要：

  原肌球蛋白受体激酶（TrkA / B / C）表达和信号传导失调被认为是许多神经退行性疾病的标志，包括帕金森氏病，亨廷顿氏病和阿尔茨海默氏病。已知TrkA / B / C可在多种神经源性和非神经源性人类癌症中驱动肿瘤发生和转移潜力。合适的正电子发射断层扫描（PET）放射性配体的开发将允许在体内探索这种多功能的潜在治疗靶标。在此，对6-（2-（3-氟苯基）吡咯烷-1-基）咪唑并[1,2 - b ]哒嗪-3-酰胺铅结构的酰胺部分进行合理重塑，以适应有效的氟18标记铅皮摩尔IC 50鉴定一系列氟化Trk抑制剂。随后的代表性放射性标记抑制剂[ 18 F] 16（[ 18 F]-（±）-IPMICF6）和[ 18 F] 27（[ 18 F]-（±）-IPMICF10）构成了新型的约2至3的先导放射性配体-与以前的铅示踪剂相比，TrkB / C效能提高了几个数量级，并显示出了良好的选择性和物理化学参数，可转化为体内PET显像剂。

  DOI：

  10.1039/c5md00388a

文献信息

• Derisking the Cu-Mediated ¹⁸F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands
  作者：Nicholas J. Taylor、Enrico Emer、Sean Preshlock、Michael Schedler、Matthew Tredwell、Stefan Verhoog、Joel Mercier、Christophe Genicot、Véronique Gouverneur

  DOI：10.1021/jacs.7b03131

  日期：2017.6.21

  Molecules labeled with fluorine-18 (18F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of 18F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach

  用氟 18 (18F) 标记的分子用于正电子发射断层扫描，以可视化、表征和测量体内的生物过程。尽管最近在将 18F 掺入芳烃方面取得了进展，但开发通用且有效的方法来标记药物发现计划所需的放射性配体仍然是一项重大任务。这个完整的描述描述了杂环正电子发射断层扫描 (PET) 放射性配体的放射合成方法，使用铜介导的 18F 氟化芳基硼试剂与 18F 氟化物作为模型反应。该方法基于一项研究，该研究检查了药物开发中常用的杂环的存在如何影响代表性芳基硼试剂的 18F-氟化效率，以及超过 50 种（杂）芳基硼酸酯的标记。这组数据允许将这种去风险策略应用于七种结构复杂的药物相关含杂环分子的成功放射合成。
• Antibacterial compound
  申请人：SANKYO COMPANY, LIMITED

  公开号：US20030171330A1

  公开（公告）日：2003-09-11

  A compound of formula (I) 1 wherein R 1 and R 2 represent a hydrogen atom or an aryl, a heterocyclic, an alkyl or an alkenyl, which are optionally substituted, R 3 represents a hydrogen atom or a hydroxyl and X 1 and X 2 represent an oxygen atom, a sulfur atom or a nitrogen containing group, a pharmaceutically acceptable derivative thereof or a salt thereof. A pharmaceutical composition comprising the compound for the prevention or treatment of a bacterial infection. A method for the prevention or treatment of a bacterial infection in a warm-blooded animal comprising administering a pharmacologically effective amount of the compound.

  式（I）的化合物，其中R1和R2代表氢原子或芳基、杂环基、烷基或烯基，可以是可选择取代的；R3代表氢原子或羟基；X1和X2代表氧原子、硫原子或含氮基团，其药用上可接受的衍生物或盐。包括该化合物的药物组合物，用于预防或治疗细菌感染。一种方法，用于在温血动物中预防或治疗细菌感染，包括给予该化合物的药理有效量。
• First GPR119 PET Imaging Ligand: Synthesis, Radiochemistry, and Preliminary Evaluations
  作者：Avinash H. Bansode、Naresh Damuka、Nagaraju Bashetti、Krishna Kumar Gollapelli、Ivan Krizan、Bhuvanachandra Bhoopal、Mack Miller、Shanmukha Kumar JV、Christopher T. Whitlow、Donald McClain、Tao Ma、Matthew J. Jorgensen、Kiran Kumar Solingapuram Sai

  DOI：10.1021/acs.jmedchem.3c00720

  日期：2023.7.13

  levels in vivo could significantly advance GPR119-based drug development strategies including target engagement, occupancy, and distribution studies. To date, no positron emission tomography (PET) ligands are available to image GPR119. In this paper, we report the synthesis, radiolabeling, and preliminary biological evaluations of a novel PET radiotracer [18F]KSS3 to image GPR119. PET imaging will provide

  G 蛋白偶联受体 119 (GPR119) 已成为治疗 2 型糖尿病的有希望的靶点。激活 GPR119 可改善葡萄糖稳态，同时抑制食欲和体重增加。测量体内GPR119 水平可以显着推进基于 GPR119 的药物开发策略，包括靶点参与、占用和分布研究。迄今为止，尚无正电子发射断层扫描 (PET) 配体可用于 GPR119 成像。在本文中，我们报告了一种新型 PET 放射性示踪剂 [ 18 F]KSS3 对 GPR119 进行成像的合成、放射性标记和初步生物学评估。 PET 成像将提供有关 GPR119 随糖尿病血糖负荷变化的信息以及 GPR119 激动剂作为抗糖尿病药物的功效。我们的结果证明 [ 18 F]KSS3 具有高放射化学纯度、比活性、细胞摄取以及胰腺、肝脏和肠道区域的体内和离体摄取，并且具有高 GPR119 表达。用非放射性 KSS3 进行细胞预处理、啮齿动物 PET 成像、生物分
• NOVEL A-500359 DERIVATIVES
  申请人：Sankyo Company, Limited

  公开号：EP1209166A1

  公开（公告）日：2002-05-29

  The present invention relates to a compound of formula (I) (wherein R1 and R2 represent an aryl group, a heterocyclic group, an alkyl group, an alkenyl group and the like which are optionally substituted, R3 represents a hydrogen atom or a hydroxyl group, and X1 and X2 represent an oxygen atom or a sulfur atom, or a nitrogen atom which may be substituted), a pharmaceutically acceptable derivative thereof or a salt thereof. The present invention also relates to a pharmaceutical composition comprising a compound described above as an active ingredient for the prevention or treatment of bacterial infections. The present invention includes the use of a compound described above in order to prepare a medicament effective in the prevention or treatment of bacterial infections. The present invention is concerned with a method for the prevention or treatment of bacterial infections in warm-blooded animals comprising administering a pharmacologically effective amount of a compound described above to them.

  本发明涉及一种式(I)化合物（其中 R1 和 R2 代表芳基、杂环基、烷基、烯基等任选被取代的基团，R3 代表氢原子或羟基，X1 和 X2 代表氧原子或硫原子或可被取代的氮原子）、其药学上可接受的衍生物或其盐。 本发明还涉及一种药物组合物，其中包含上述化合物作为活性成分，用于预防或治疗细菌感染。 本发明包括使用上述化合物制备有效预防或治疗细菌感染的药物。 本发明涉及一种预防或治疗温血动物细菌感染的方法，包括给温血动物服用药理有效量的上述化合物。
• Synthesis and evaluation of 18F-labeled ATP competitive inhibitors of topoisomerase II as probes for imaging topoisomerase II expression
  作者：Pierre Daumar、Brian M. Zeglis、Nicholas Ramos、Vadim Divilov、Kuntal Kumar Sevak、NagaVaraKishore Pillarsetty、Jason S. Lewis

  DOI：10.1016/j.ejmech.2014.09.019

  日期：2014.10

  Type II topoisomerase (Topo-II) is an ATP-dependent enzyme that is essential in the transcription, replication, and chromosome segregation processes and, as such, represents an attractive target for cancer therapy. Numerous studies indicate that the response to treatment with Topo-II inhibitors is highly dependent on both the levels and the activity of the enzyme. Consequently, a non-invasive assay to measure tumoral Topo-II levels has the potential to differentiate responders from non-responders. With the ultimate goal of developing a radiofluorinated tracer for positron emission tomography (PET) imaging, we have designed, synthesized, and evaluated a set of fluorinated compounds based on the structure of the ATP-competitive Topo-II inhibitor QAP1. Compounds 18 and 19b showed inhibition of Topo-II in in vitro assays and exhibited moderate, Topo-II level dependent cytotoxicity in SK-BR-3 and MCF-7 cell lines. Based on these results, F-18-labeled analogs of these two compounds were synthesized and evaluated as PET probes for imaging Topo-II overexpression in mice bearing SK-BR-3 xenografts. [F-18]-18 and [F-18]-19b were synthesized from their corresponding protected tosylated derivatives by fluorination and subsequent deprotection. Small animal PET imaging studies indicated that both compounds do not accumulate in tumors and exhibit poor pharmacokinetics, clearing from the blood pool very rapidly and getting metabolized over. The insights gained from the current study will surely aid in the design and construction of future generations of PET agents for the non-invasive delineation of Topo-II expression. (c) 2014 Elsevier Masson SAS. All rights reserved.