(alphaR)-1-[2-(4-氟苯基)乙基]-alpha-(3-羟基-2-甲氧基苯基)-4-哌啶甲醇 | 189192-18-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: (alphaR)-1-[2-(4-氟苯基)乙基]-alpha-(3-羟基-2-甲氧基苯基)-4-哌啶甲醇
• 英文名称: (R)-(+)-α-(3-hydroxy-2-methoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanone
• 英文别名: (R)-(+)-α-(3-hydroxy-2-methoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol；(R)-(3-hydroxy-2-methoxyphenyl)-(1-(2-p-fluorophenylethyl)-piperidin-4-yl)-methanol；(R)-3-((1-(4-fluorophenethyl)piperidin-4-yl)(hydroxy)methyl)-2-methoxyphenol；MDL 105725；3-[(R)-[1-[2-(4-fluorophenyl)ethyl]-4-piperidinyl]-hydroxymethyl]-2-methoxyphenol；3-[(R)-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]-hydroxymethyl]-2-methoxyphenol
• CAS: 189192-18-5
• 化学式: C₂₁H₂₆FNO₃
• 分子量: 359.441
• InChiKey: DVDGOKMQDYFKFY-HXUWFJFHSA-N

物化性质

• 沸点：
  522.1±50.0 °C(Predicted)
• 密度：
  1.202±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  52.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (alphaR)-1-[2-(4-氟苯基)乙基]-alpha-(3-羟基-2-甲氧基苯基)-4-哌啶甲醇 在 sodium hydride 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.5h， 生成
  参考文献：
  名称：

  血清素（5-HT）5-HT 2A受体（5-HT 2A R）拮抗剂M100907的合成及其功能衍生物

  摘要：

  将两个已知的受体配体连接在一起的方法被用作有价值的方法，该方法用作研究G蛋白偶联受体（GPCR）系统的分子探针。具有可用于与其他配体连接的功能的选择性配体可用于开发新型拮抗剂和激动剂。此类分子还可以连接到报告分子（例如荧光团）上，以研究GPCR二聚化及其在信号传导中的作用。高选择性5-羟色胺（5-HT）5-HT 2A受体（5-HT 2AR）拮抗剂M100907（volinanserin）在治疗神经和精神疾病方面具有临床意义。在这里，我们合成了活性最高的（+）-M100907对映异构体以及一系列具有炔烃或叠氮化物的衍生物。由这些基团的偶极环加成产生的三唑不干扰二价配体充当拮抗剂的能力。因此，我们合成了许多化合物，这些化合物将被证明可用于阐明5-HT 2A R在中枢神经系统中的作用。

  DOI：

  10.1016/j.bmcl.2018.02.058
• 作为产物：
  描述：

  在 水 、 potassium carbonate 作用下， 反应 42.0h， 以74%的产率得到(alphaR)-1-[2-(4-氟苯基)乙基]-alpha-(3-羟基-2-甲氧基苯基)-4-哌啶甲醇
  参考文献：
  名称：

  An efficient synthesis of the precursors of [11C]MDL 100907 labeled in two specific positions

  摘要：

  An efficient, integrated route for the synthesis of two precursors of [C-11]MDL 100907 labeled in the 2'- or 3'-methoxy position is reported. The synthesis involved a one-pot, two-step process to transform the intermediate esters to ketones and subsequent resolution of the racemic alcohols to their respective enantiomers. The resolved, enantiomerically pure phenol precursors were reacted with high specific activity [C-11]methyl iodide to produce [C-11]MDL 100907 labeled in two specific positions.

  DOI：

  10.1002/(sici)1099-1344(199910)42:10<949::aid-jlcr253>3.0.co;2-s

文献信息

• A practical synthesis of the serotonin 5-HT2a receptor antagonist mdl 100907, its enantiomer and their 3-phenolic derivatives as precursors for [11c]labeled pet ligands
  作者：Thomas Ullrich、Kenner C Rice

  DOI：10.1016/s0968-0896(00)00175-9

  日期：2000.10

  the 3-phenolic precursor of MDL 100907, a selective 5-HT2A receptor antagonist, is described. The route was also applied to the enantiomeric series, thus affording the direct precursors of both 3-[11C]MDL 100907 and its enantiomer as ligands for positron emission tomography. Similar methodology was developed for the direct synthesis of MDL 100907 and its enantiomer, MDL 100009. The routes utilized

  描述了MDL 100907的3-酚前体（一种选择性的5-HT2A受体拮抗剂）的实际合成方法。该方法也适用于对映体系列，从而提供了3- [11C] MDL 100907及其对映体的直接前体作为正电子发射断层扫描的配体。开发了用于直接合成MDL 100907及其对映体MDL 100009的类似方法。该路线利用了对映体过量至少98％的N-nor中间体的经典旋光拆分方法，并轻松获得了数克重的多种手性前体N-和3-O-取代的对映异构体。
• [11C]MDL 100907, a radioligand for selective imaging of 5-HT2A receptors with positron emission tomography
  作者：Camilla Lundkvist、Christer Halldin、Nathalie Ginovart、Svante Nyberg、Carl-Gunnar Swahn、Albert A. Carr、Francoise Brunner、Lars Farde

  DOI：10.1016/0024-3205(96)00013-6

  日期：1996.2

  The highly selective 5-HT2A receptor antagonist, MDL 100907 ((R)-(+)-4 -(l-hydroxy-1-(2,3-dimethoxyphenyl)methyl)-N -2-(4-fluorophenylethyl)piperidine), was labeled with 11C for Positron Emission Tomography (PET) studies. After i.v. injection of (R)-(+)-[3-OCH3-11C]MDL 100907 [11C]MDL 100907) in Cynomolgus monkeys a marked accumulation in the 5-HT2A receptor rich neocortical regions was obtained with

  高选择性5-HT2A受体拮抗剂MDL 100907（（R）-（+）-4-（1-羟基-1-（2,3-二甲氧基苯基）甲基）-N -2-（4-氟苯基乙基）哌啶）被标记为11C，用于正电子发射断层扫描（PET）研究。在食蟹猴中静脉内注射（R）-（+）-[3-OCH3-11C] MDL 100907 [11C] MDL 100907）后，以新皮层与小脑的比例获得了富含5-HT2A受体的新皮层区域的明显积累。 60-80分钟后的3.5-4.5。在新皮层区域，在40-60分钟内发生了短暂的平衡。注射酮色林后，新皮层中的放射性降低，但小脑中的放射性降低，这表明注射[11C] MDL 100907后的新皮层放射性代表与5-HT2A受体的特异性结合。
• Automated synthesis of <i>(R)</i> ‐[ ¹⁸ F]MH.MZ on the iPhase Flexlab reaction platform
  作者：Adam J. Rosenberg、Yiu‐Yin Cheung、Fei Liu、Todd E. Peterson、James Silverman、Ciaran M. Considine、Daniel O. Claassen

  DOI：10.1002/jlcr.3975

  日期：2022.6.30

  (R)-[18F]MH.MZ ([18F]MH.MZ) is a promising positron emission tomography (PET) radiotracer for in vivo study of the 5-HT2A receptor. To facilitate clinical trials, a fully automated radiosynthesis procedure for [18F]MH.MZ was developed using commercially available materials on the iPhase Flexlab module. The overall synthesis time was 100 min with a radiochemical yield of 7 ± 0.9% (n = 3). The radiochemical purity was greater than 99% for [18F]MH.MZ with a molar activity of 361 ± 57 GBq/μmol (n = 3). The protocol described herein reliably provides [18F]MH.MZ that meets all relevant release criteria for a GMP radiopharmaceutical.

  (R)-[18F]MH.MZ（[18F]MH.MZ）是一种很有前途的正电子发射断层扫描（PET）放射性示踪剂，可用于体内 5-HT2A 受体的研究。为促进临床试验，我们使用市售材料在 iPhase Flexlab 模块上开发了[18F]MH.MZ 的全自动放射合成程序。总体合成时间为 100 分钟，放射化学收率为 7 ± 0.9% （n = 3）。[18F]MH.MZ的放射化学纯度大于99%，摩尔活性为361 ± 57 GBq/μmol（n = 3）。本文所述方案可靠地提供了符合 GMP 放射性药物所有相关释放标准的 [18F]MH.MZ。
• Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET
  作者：Matthias M. Herth、Vasko Kramer、Markus Piel、Mikael Palner、Patrick J. Riss、Gitte M. Knudsen、Frank Rösch

  DOI：10.1016/j.bmc.2009.03.021

  日期：2009.4

  Radiolabelled piperidine derivatives such as [C-11] MDL 100907 and [F-18] altanserin have played an important role in diagnosing malfunction in the serotonergic neurotransmission. A variety of novel piperidine MDL 100907 derivatives, possible to label with F-18-fluorine, were synthesized to improve molecular imaging properties of [C-11] MDL 100907. Their in vitro affinities to a broad spectrum of neuroreceptors and their lipophilicities were determined and compared to the clinically used reference compounds MDL 100907 and altanserin. The novel compounds MA-1 (53) and (R)-MH.MZ (56) show K-i-values in the nanomolar range towards the 5-HT2A receptor and insignificant binding to other 5-HT receptor sub-types or receptors. Interestingly, compounds MA-1 (53), MH.MZ (55) and (R)-MH.MZ (56) provide a receptor selectivity pro. le similar to MDL 100907. These compounds could possibly be preferable antagonistic F-18-tracers for visualization of the 5-HT2A receptor status. Medium affine compounds (VK-1 (32), (51), (52), (54)) were synthesized and have K-i values between 30 and 120 nM. All promising compounds show logP values between 2 and 3, that is, within the range of those for the established radiotracers altanserin and MDL 100907. The novel compounds MA-1 (53) and (R)-MH.MZ (56) thus appear to be promising high affine and selective tracers of F-18-labelled analogues for 5-HT2A imaging with PET. (C) 2009 Elsevier Ltd. All rights reserved.
• Lundkvist, C.; Sandell, J.; Nagren, K., Journal of labelled compounds and radiopharmaceuticals, 1997, vol. 40, p. 583 - 585
  作者：Lundkvist, C.、Sandell, J.、Nagren, K.、Pike, V. W.、Swahn, C.-G.、et al.

  DOI：——

  日期：——