N-{2-[4-(2'-methoxyphenyl)piperazinyl]ethyl}-N-(2-pyridyl)-N-(4'-fluoromethylcyclohexane)carboxamide | 946530-09-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-{2-[4-(2'-methoxyphenyl)piperazinyl]ethyl}-N-(2-pyridyl)-N-(4'-fluoromethylcyclohexane)carboxamide
• 英文别名: Mefway；4-(fluoromethyl)-N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexane-1-carboxamide
• CAS: 946530-09-2
• 化学式: C₂₆H₃₅FN₄O₂
• 分子量: 454.588
• InChiKey: BQGLPDFQLBNUGU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  48.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-乙酰基环己烷羧酸 在 lithium aluminium tetrahydride 、 草酰氯 、 二乙胺基三氟化硫 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 48.5h， 生成 N-{2-[4-(2'-methoxyphenyl)piperazinyl]ethyl}-N-(2-pyridyl)-N-(4'-fluoromethylcyclohexane)carboxamide
  参考文献：
  名称：

  Synthesis and evaluation of mefway analogs as ligands for serotonin 5HT1A receptors

  摘要：

  F-18-Mefway (N-{2-[4-(2'-methoxyphenyl)piperazinyl]ethyl}-N-(2-pyridyl)-N-(4'-F-18-fluoro-methylcyclohexane)carboxamide) was developed and evaluated for use as a PET ligand for imaging 5-HT1A receptors. Ongoing studies of F-18-Mefway have shown it to be an effective PET radiotracer. We have synthesized isomers of Mefway by changing the position of the methyl group in attempts to evaluate stability for imaging purposes. 2-Methyl-, 3-methyl-, and 4-methyl-cyclohexane-1-carboxylic acids and 3-carbomethoxy-, 4-carbomethoxycyclohexane-1-carboxylic acids were coupled with WAY-100634 to provide the methylcyclohexyl derivatives (2-, 3-, and 4-methyl). Mefway and 3-Mefway analogs were prepared by reduction of carbomethoxy- derivatives followed by fluorination. In vitro binding affinities for the methylated derivatives in rat brain homogenates were found to be 10.4 nM (2-methyl), 77 nM (3-methyl), and 21.5 nM (4-methyl). Binding affinity of 3-Mefway and 4-Mefway was found to be 17.4 nM and 6.26 nM, respectively. Our results suggest that 3-methyl/3-fluoromethyl substituent has approx. threefold lower affinities compared to the 4-methyl/4-fluoromethyl substituent.

  DOI：

  10.1007/s00044-014-1238-z

文献信息

• COMPOSITIONS AND METHODS RELATED TO SEROTONIN 5-HT1A RECEPTORS
  申请人：Mukherjee Jogeshwar

  公开号：US20070196271A1

  公开（公告）日：2007-08-23

  Contemplated substituted arylpiperazinyl compounds, and most preferably 18 F-Mefway, exhibit desirable in vitro and in vivo binding characteristics to the 5-HT1A receptor. Among other advantageous parameters, contemplated compounds retain high binding affinity, display optimal lipophilicity, and are radiolabeled efficiently with 18 F-fluorine in a single step. Still further, contemplated compounds exhibit high target to non-target ratios in receptor-rich regions both in vitro and in vivo, and selected compounds can be effectively and sensitively displaced by serotonin, thus providing a quantitative tool for measuring 5-HT1A receptors and serotonin concentration changes in the living brain.

  考虑替代芳基哌嗪类化合物，最好是18F-Mefway，展示出理想的体外和体内与5-HT1A受体结合特性。在其他有利参数中，考虑的化合物保留高结合亲和力，显示出最佳的亲脂性，并且能够通过单步骤高效地用18F-氟标记。此外，考虑的化合物在体外和体内的受体丰富区域展现出高的靶向与非靶向比例，而且选定的化合物可以被5-羟色胺有效敏感地置换，从而提供了一种用于测量活体大脑中5-HT1A受体和5-羟色胺浓度变化的定量工具。
• 5HT1A ANTAGONIST USEFUL FOR IN VIVO IMAGING
  申请人：Newington Ian Martin

  公开号：US20140140928A1

  公开（公告）日：2014-05-22

  The present invention provides a novel compound of formula (I) useful for in vivo imaging of 5-HT 1 A receptors in a subject. Also provided by the present invention is a precursor compound useful in the preparation of the compound of the invention, as well as said method of preparation. The present invention additionally provides methods for the use of the compound of the invention in an in vivo imaging method, and use of that in vivo imaging method in diagnosis and therapy monitoring.

  本发明提供了一种新的化合物（I）的公式，用于在受试者中体内成像5-HT1A 受体。本发明还提供了一种前体化合物，用于制备本发明的化合物，以及制备方法。本发明还提供了使用该化合物的方法，用于体内成像方法，并将该体内成像方法用于诊断和治疗监测。
• NOVEL SYNTHESIS METHOD
  申请人：GE HEALTHCARE LIMITED

  公开号：US20150133663A1

  公开（公告）日：2015-05-14

  The present invention relates to a method of making compounds having affinity for the 1 A subtype of the serotonin receptor, i.e. 5HT 1A . The method of the present invention provides advantages over the known methods of synthesis. The compounds obtained by the method of the invention have use in therapeutic methods. The compounds of the invention may also optionally compose a moiety suitable for detection by an in vivo imaging procedure and as such these compounds have use in in vivo imaging methods. The compounds have particular use in the treatment and diagnosis of various neurological and/or psychiatric disorders.

  本发明涉及一种制备具有亲和力的化合物的方法，该化合物对于5HT1A即血清素受体的1A亚型具有亲和力。本发明的方法相对于已知的合成方法具有优势。通过本发明的方法获得的化合物在治疗方法中有用。本发明的化合物也可以选择性地组成适合通过体内成像程序检测的基团，因此这些化合物在体内成像方法中有用。这些化合物在治疗和诊断各种神经和/或精神障碍方面具有特殊用途。
• US7731940B2
  申请人：——

  公开号：US7731940B2

  公开（公告）日：2010-06-08
• USRE43688E1
  申请人：——

  公开号：USRE43688E1

  公开（公告）日：2012-09-25