1-(2-((2R)-1-[(2-[(18)F]-fluorophenyl)sulfonyl]pyrrolidin-2-yl)ethyl)-4-methylpiperidine | 1314696-37-1

• 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: 1-(2-((2R)-1-[(2-[(18)F]-fluorophenyl)sulfonyl]pyrrolidin-2-yl)ethyl)-4-methylpiperidine
• 英文别名: 1-(2-{(2R)-1-[(2-[18F]Fluorophenyl)sulfonyl]pyrrolidin-2-yl}ethyl)-4-methylpiperidine；1-[2-[(2R)-1-(2-(18F)fluoranylphenyl)sulfonylpyrrolidin-2-yl]ethyl]-4-methylpiperidine
• CAS: 1314696-37-1
• 化学式: C₁₈H₂₇FN₂O₂S
• 分子量: 353.491
• InChiKey: MESXUKOOJXWYFP-ZREINDOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  49
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (R)-吡咯烷-2-乙酸 在 lithium aluminium tetrahydride 、 potassium [¹⁸F]fluoride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.67h， 生成 1-(2-((2R)-1-[(2-[(18)F]-fluorophenyl)sulfonyl]pyrrolidin-2-yl)ethyl)-4-methylpiperidine
  参考文献：
  名称：

  Synthesis and biological evaluation of potential 5-HT7 receptor PET radiotracers

  摘要：

  Brain serotonin 7 receptor (5-HT7) is involved in several mood disorders and drug candidates targeting this subtype are currently in development. Positron emission tomography (PET) is a molecular imaging modality offering great promise for accelerating the process from preclinical discovery to clinical phases. As no PET radiopharmaceutical has yet been used successfully to study the 5-HT7 receptor in vivo, our objective is to develop the first 5-HT7 fluorine-18 labeled radiotracer.Four structural analogs of SB269970, a specific 5-HT7 receptor antagonist, divided in FP3 series and FPMP series were synthesized. Their antagonist effects were investigated by cellular functional assay. Nitro-precursors of these analogs were radiolabeled via a [F-18(-)]nucleophilic substitution and in vitro autoradiographies were performed in rat brain.Chemical and radiochemical purities of fluorine radiotracers were >99% with specific activities in 40 -129 GBq/mu mole range. The four derivates presented antagonism potencies toward 5-HT7 receptors (PKB) between 7.8 and 8.8. The four PET radiotracers had suitable characteristic for 5-HT7 receptor probing in vitro even if the FP3 series seemed to be more specific for this receptor. These results encourage us to pursue in vivo studies. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.010

文献信息

• Evaluation of [¹⁸ F]2FP3 in pigs and non-human primates
  作者：Hanne D. Hansen、Cristian C. Constantinescu、Olivier Barret、Matthias M. Herth、Janus H. Magnussen、Szabolcs Lehel、Agnete Dyssegaard、Julie Colomb、Thierry Billard、Luc Zimmer、Gilles Tamagnan、Gitte M. Knudsen

  DOI：10.1002/jlcr.3692

  日期：2019.1

  So far, no suitable 5-HT7R radioligand exists for clinical positron emission tomography (PET) imaging. [18F]2FP3 was first tested in vivo in cats, and the results were promising for further evaluations. Here, we evaluate the radioligand in pigs and non-human primates (NHPs). Furthermore, we investigate species differences in 5-HT7R binding with [3H]SB-269970 autoradiography in post-mortem pig, NHP, and human brain tissue. Specific binding of [18F]2FP3 was investigated by intravenous administration of the 5-HT7R specific antagonist SB-269970. [3H]SB-269970 autoradiography was performed as previously described. [18F]2FP3 was synthesized in an overall yield of 35% to 45%. High brain uptake of the tracer was found in both pigs and NHPs; however, pretreatment with SB-269970 only resulted in decreased binding of 20% in the thalamus, a 5-HT7R–rich region. Autoradiography on post-mortem pig, NHP, and human tissues revealed that specific binding of [3H]SB-269970 was comparable in the thalamus of pig and NHP. Despite the high uptake of [18F]2FP3 in both species, the binding could only be blocked to a limited degree with the 5-HT7R antagonists. We speculate that the affinity of the radioligand is too low for imaging the 5-HT7Rs in vivo and that part of the PET signal arises from targets other than the 5-HT7R.

  迄今为止，尚不存在适合临床正电子发射断层扫描（PET）成像的5-HT7R放射性配体。 [18F]2FP3 首次在猫体内进行了测试，结果有望用于进一步评估。在这里，我们评估了猪和非人灵长类动物 (NHP) 的放射性配体。此外，我们利用 [3H]SB-269970 放射自显影技术研究了死后猪、NHP 和人脑组织中 5-HT7R 结合的物种差异。通过静脉内施用5-HT7R特异性拮抗剂SB-269970来研究[18F]2FP3的特异性结合。如前所述进行[ 3 H]SB-269970放射自显影。 [18F]2FP3的合成总产率为35%至45%。在猪和 NHP 中发现示踪剂的脑部摄取量较高；然而，SB-269970 预处理仅导致丘脑（富含 5-HT7R 的区域）的结合减少 20%。对死后猪、NHP 和人体组织的放射自显影显示，[3H]SB-269970 的特异性结合在猪和 NHP 的丘脑中相当。尽管这两个物种对[18F]2FP3的摄取量很高，但5-HT7R拮抗剂只能在有限程度上阻断这种结合。我们推测放射性配体的亲和力太低，无法在体内对 5-HT7R 进行成像，并且部分 PET 信号来自 5-HT7R 以外的靶标。
• Synthesis and biological evaluation of potential 5-HT7 receptor PET radiotracers
  作者：Julien Andries、Laetitia Lemoine、Didier Le Bars、Luc Zimmer、Thierry Billard

  DOI：10.1016/j.ejmech.2011.05.010

  日期：2011.8

  Brain serotonin 7 receptor (5-HT7) is involved in several mood disorders and drug candidates targeting this subtype are currently in development. Positron emission tomography (PET) is a molecular imaging modality offering great promise for accelerating the process from preclinical discovery to clinical phases. As no PET radiopharmaceutical has yet been used successfully to study the 5-HT7 receptor in vivo, our objective is to develop the first 5-HT7 fluorine-18 labeled radiotracer.Four structural analogs of SB269970, a specific 5-HT7 receptor antagonist, divided in FP3 series and FPMP series were synthesized. Their antagonist effects were investigated by cellular functional assay. Nitro-precursors of these analogs were radiolabeled via a [F-18(-)]nucleophilic substitution and in vitro autoradiographies were performed in rat brain.Chemical and radiochemical purities of fluorine radiotracers were >99% with specific activities in 40 -129 GBq/mu mole range. The four derivates presented antagonism potencies toward 5-HT7 receptors (PKB) between 7.8 and 8.8. The four PET radiotracers had suitable characteristic for 5-HT7 receptor probing in vitro even if the FP3 series seemed to be more specific for this receptor. These results encourage us to pursue in vivo studies. (C) 2011 Elsevier Masson SAS. All rights reserved.