(3-(2-fluoroethoxy)-2-methoxy-phenyl)-(piperidin-4-yl)-methanol | 1160298-40-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (3-(2-fluoroethoxy)-2-methoxy-phenyl)-(piperidin-4-yl)-methanol
• CAS: 1160298-40-7
• 化学式: C₁₅H₂₂FNO₃
• 分子量: 283.343
• InChiKey: NRASSTFGKVVVAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.08
• 重原子数：
  20.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  50.72
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (3-(2-fluoroethoxy)-2-methoxy-phenyl)-(piperidin-4-yl)-methanol 在 potassium carbonate 、 三氟乙酸 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (1-(2-aminoethyl)piperidin-4-yl)(3-(2-fluoroethoxy)-2-methoxyphenyl)methanol
  参考文献：
  名称：

  Research Letter: Structural Combination of Established 5-HT2A Receptor Ligands: New Aspects of the Binding Mode

  摘要：

  MH.MZ, MDL 100907, and altanserin are structurally similar 4‐benzoyl‐piperidine derivatives and are well accommodated to receptor interaction models. We combined structural elements of different high‐affinity and selective 5‐HT2A antagonists, as MH.MZ, altanserin, and SR 46349B, to improve the binding properties of new compounds. Three new derivatives were synthesized with a 4‐benzoyl‐piperidine moiety as the lead structure. The in vitro affinity of the novel compounds was determined by a [3H]MDL 100907 competition binding assay. The combination of MH.MZ and SR 46349B resulted in a compound (8) with a moderate affinity toward the 5‐HT2A receptor (Ki = 57 nm). The remarkably reduced affinity of other compounds (4a), (4b), and (4c) (Ki = 411, 360 and 356 nm respectively) indicates that MH.MZ can only bind to the 5‐HT2A receptor with the p‐fluorophenylethyl residue in a sterically restricted hydrophobic binding pocket.

  DOI：

  10.1111/j.1747-0285.2010.01011.x
• 作为产物：
  描述：

  4-(3-(2-fluoroethoxy)-2-methoxybenzoyl)-piperidine 在 sodium tetrahydroborate 、 ammonium hydroxide 作用下， 以 甲醇 为溶剂， 以56%的产率得到(3-(2-fluoroethoxy)-2-methoxy-phenyl)-(piperidin-4-yl)-methanol
  参考文献：
  名称：

  Synthesis and in vitro affinities of various MDL 100907 derivatives as potential 18F-radioligands for 5-HT2A receptor imaging with PET

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2009.03.021