[2-methoxy-3-[(1,1-dimethylethyldiphenylsilyl)oxy]phenyl][1-[2-(4-fluorophenyl)ethyl]-4-piperidinyl]methanone | 252364-41-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [2-methoxy-3-[(1,1-dimethylethyldiphenylsilyl)oxy]phenyl][1-[2-(4-fluorophenyl)ethyl]-4-piperidinyl]methanone
• 英文别名: 4-(2-methoxy-3-(t-butyldiphenylsilyloxy)-benzoyl)-1-(2-p-fluorophenylethyl)-piperidine；[3-[Tert-butyl(diphenyl)silyl]oxy-2-methoxyphenyl]-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]methanone
• CAS: 252364-41-3
• 化学式: C₃₇H₄₂FNO₃Si
• 分子量: 595.829
• InChiKey: DYUGPGVOKVBYBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.91
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  1-Boc-4-[甲氧基(甲基)氨基甲酰]哌嗪 在 正丁基锂 、 三氟乙酸 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 [2-methoxy-3-[(1,1-dimethylethyldiphenylsilyl)oxy]phenyl][1-[2-(4-fluorophenyl)ethyl]-4-piperidinyl]methanone
  参考文献：
  名称：

  推定的5-HT2A / mGlu2受体复合物的异二价配体的设计，合成和药理学表征。

  摘要：

  我们报告了针对5-HT 2A拮抗剂MDL-100,907和mGlu 2 ago-PAM JNJ-42491293的推定异聚5 -HT 2A / mGlu 2受体复合物的第一系列异二价配体的合成。使用Ca 2在表达5-HT 2A-，mGlu 2 / Gqo5-，5-HT 2A / mGlu 2-和5-HT 2A / mGlu 2 / Gqo5的HEK293细胞中表征一价和异二价配体的功能特性。+成像分析和[ 3H]酮色林结合测定。在5-HT 2A / mGlu 2和5-HT 2A / mGlu 2 / Gqo5细胞中的两个受体之间观察到明显的功能性串扰。虽然合成的一价配体保留了5-HT 2A拮抗剂和mGlu 2 ago-PAM的功能，但七个二价配体抑制了5-HT 2A / mGlu 2细胞中5-HT诱导的应答以及5-HT和Glu诱导的应答5-HT 2A / mGlu 2中的响应/ Gqo5细

  DOI：

  10.1021/acs.jmedchem.0c01058

文献信息

• 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.
• Design, Synthesis, and Pharmacological Characterization of Heterobivalent Ligands for the Putative 5-HT_2A/mGlu₂ Receptor Complex
  作者：Christian B. M. Poulie、Na Liu、Anders A. Jensen、Lennart Bunch

  DOI：10.1021/acs.jmedchem.0c01058

  日期：2020.9.10

  We report the synthesis of the first series of heterobivalent ligands targeting the putative heteromeric 5-HT2A/mGlu2 receptor complex, based on the 5-HT2A antagonist MDL-100,907 and the mGlu2 ago-PAM JNJ-42491293. The functional properties of monovalent and heterobivalent ligands were characterized in 5-HT2A-, mGlu2/Gqo5-, 5-HT2A/mGlu2-, and 5-HT2A/mGlu2/Gqo5-expressing HEK293 cells using a Ca2+ imaging

  我们报告了针对5-HT 2A拮抗剂MDL-100,907和mGlu 2 ago-PAM JNJ-42491293的推定异聚5 -HT 2A / mGlu 2受体复合物的第一系列异二价配体的合成。使用Ca 2在表达5-HT 2A-，mGlu 2 / Gqo5-，5-HT 2A / mGlu 2-和5-HT 2A / mGlu 2 / Gqo5的HEK293细胞中表征一价和异二价配体的功能特性。+成像分析和[ 3H]酮色林结合测定。在5-HT 2A / mGlu 2和5-HT 2A / mGlu 2 / Gqo5细胞中的两个受体之间观察到明显的功能性串扰。虽然合成的一价配体保留了5-HT 2A拮抗剂和mGlu 2 ago-PAM的功能，但七个二价配体抑制了5-HT 2A / mGlu 2细胞中5-HT诱导的应答以及5-HT和Glu诱导的应答5-HT 2A / mGlu 2中的响应/ Gqo5细
• 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.