(+/-)-α-[2-methoxy-3-[(1,1-dimethylethyldiphenylsilyl)oxy]phenyl]-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanone | 252364-42-4

• 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: (+/-)-α-[2-methoxy-3-[(1,1-dimethylethyldiphenylsilyl)oxy]phenyl]-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanone
• 英文别名: (2-methoxy-3-(t-butyldiphenylsilyloxy)-phenyl)-(1-(2-p-fluorophenylethyl)-piperidine-4-yl)-methanol；(2-methoxy-3-(t-butyldiphenylsilyloxy)-phenyl)-(1-(2-p-fluorophenylethyl)-piperidin-4-yl)-methanol；[3-[Tert-butyl(diphenyl)silyl]oxy-2-methoxyphenyl]-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]methanol
• CAS: 252364-42-4
• 化学式: C₃₇H₄₄FNO₃Si
• 分子量: 597.845
• InChiKey: RONHWUDXYGLHIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.76
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  41.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+/-)-α-[2-methoxy-3-[(1,1-dimethylethyldiphenylsilyl)oxy]phenyl]-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanone 在 4-二甲氨基吡啶 、 水 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 氯仿 为溶剂， 反应 62.0h， 生成 (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
• 作为产物：
  描述：

  [2-methoxy-3-[(1,1-dimethylethyldiphenylsilyl)oxy]phenyl][1-[2-(4-fluorophenyl)ethyl]-4-piperidinyl]methanone 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成 (+/-)-α-[2-methoxy-3-[(1,1-dimethylethyldiphenylsilyl)oxy]phenyl]-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanone
  参考文献：
  名称：

  Total synthesis and evaluation of [18F]MHMZ

  摘要：

  Radiochemical labeling of MDL 105725 using the secondary labeling precursor 2-[F-18] fluoroethyltosylate ([F-18] FETos) was carried out in yields of similar to 90% synthesizing [F-18] MHMZ in a speci. c activity of similar to 50 MBq/ nmol with a starting activity of similar to 3 GBq. Overall radiochemical yield including [F-18] FETos synthon synthesis, [F-18] fluoroalkylation and preparing the injectable [ 18 F] MHMZ solution was 42% within a synthesis time of similar to 100 min. The novel compound showed excellent speci. c binding to the 5-HT2A receptor (K-i = 9.0 nM) in vitro and promising in vivo characteristics. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.12.054

文献信息

• Direct radiofluorination of [18F]MH.MZ for 5-HT2A receptor molecular imaging with PET
  作者：Matthias M. Herth、Vasko Kramer、Nic Gillings、Frank Rösch、Gitte M. Knudsen

  DOI：10.1002/jlcr.2947

  日期：2012.7

  Imaging the serotonin 2A neuroreceptor with positron emission tomography has been carried out with [11C]MDL 100907 and [18F]altanserin for years. Recently, the MDL 100907 analogue [18F]MH.MZ was developed by combining the increased selectivity profile of MDL 100907 and the favourable radiophysical properties of fluorine-18. Here, we want to report the synthesis of [18F]MH.MZ via direct radiofluorination. Unfortunately, the direct radiofluorination did not have any significant benefits over the indirect labelling method. This is mainly because the precursor for the direct labelling approach is not completely stable and slowly decomposes. However, only one HPLC separation is necessary for the direct 18F-nucleophilic labelling procedure, and accordingly, automation is easier. Copyright © 2012 John Wiley & Sons, Ltd.

  多年来，人们一直使用[11C]MDL 100907和[18F]阿坦色林对5-羟色胺2A神经受体进行正电子发射断层成像。最近，通过结合 MDL 100907 更高的选择性和氟-18 良好的放射物理性质，开发出了 MDL 100907 类似物 [18F]MH.MZ。在此，我们想报告通过直接放射性氟化合成 [18F]MH.MZ 的情况。遗憾的是，与间接标记法相比，直接放射性氟化法并没有明显的优势。这主要是因为直接标记法的前体并不完全稳定，分解缓慢。不过，直接 18F 亲核标记法只需一次 HPLC 分离，因此更容易实现自动化。Copyright © 2012 John Wiley & Sons, Ltd. All Rights Reserved.
• 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.
• An efficient synthesis of the precursors of [11C]MDL 100907 labeled in two specific positions
  作者：Yiyun Huang、Khalid Mahmood、Chester A. Mathis

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

  日期：1999.10

  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.
• Total synthesis and evaluation of [18F]MHMZ
  作者：Matthias M. Herth、Fabian Debus、Markus Piel、Mikael Palner、Gitte M. Knudsen、Hartmut Lüddens、Frank Rösch

  DOI：10.1016/j.bmcl.2007.12.054

  日期：2008.2

  Radiochemical labeling of MDL 105725 using the secondary labeling precursor 2-[F-18] fluoroethyltosylate ([F-18] FETos) was carried out in yields of similar to 90% synthesizing [F-18] MHMZ in a speci. c activity of similar to 50 MBq/ nmol with a starting activity of similar to 3 GBq. Overall radiochemical yield including [F-18] FETos synthon synthesis, [F-18] fluoroalkylation and preparing the injectable [ 18 F] MHMZ solution was 42% within a synthesis time of similar to 100 min. The novel compound showed excellent speci. c binding to the 5-HT2A receptor (K-i = 9.0 nM) in vitro and promising in vivo characteristics. (C) 2007 Elsevier Ltd. All rights reserved.