4-Fluoro-cyclohexanecarboxylic acid pentamethylphenylmethyl ester | 888970-51-2

• 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: 4-Fluoro-cyclohexanecarboxylic acid pentamethylphenylmethyl ester
• CAS: 888970-51-2
• 化学式: C₁₉H₂₇FO₂
• 分子量: 306.421
• InChiKey: LOTCGCRIRRNVIM-CALCHBBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  22.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  26.3
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  4-Fluoro-cyclohexanecarboxylic acid pentamethylphenylmethyl ester 在 苯甲醚 、 三氟乙酸 、 1,1-二氯甲醚 作用下， 反应 0.16h， 生成 4-Fluoro-cyclohexanecarbonyl chloride
  参考文献：
  名称：

  Synthesis and in vivo biodistribution of F-18 labeled 3-cis-, 3-trans-, 4-cis-, and 4-trans-fluorocyclohexane derivatives of WAY 100635

  摘要：

  Radioligands that are specific for the serotonin 5-HT1A receptor will be useful in characterizing the physiological action of this receptor subtype. With radioligands of varying pharmacokinetic properties, investigators can measure not only receptor density, but also the effect of endogenous serotonin concentration. To this end, three additional fluorinated analogs of WAY 100635 were prepared and evaluated as 5-HT1A receptor ligands of varyin vertical bar%1e[OK]g pharmacokinetic properties based on our previous studies. These four compounds are cis-4-fluoro-, trans-4-fluoro-, cis-3-fluoro-, and trans-3-fluoro-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-(pyridin-2-yl)cyclohexanecarboxamides (FCWAYs). All four compounds were characterized and radiolabeled with fluorine-18, a 109.7 min half-life radionuclide used in positron emission tomography. We then determined in vitro inhibition constants at the 5-HT1A receptor; in vitro metabolic profile, using rat hepatocytes and liquid chromatography/mass spectroscopy (LC/MS); and the rate of defluorination and hippocampus to cerebellum ratio ex vivo. This led to the conclusion that high affinity 4-trans-F-18 FCWAY had the best properties for measuring receptor density given its high hippocampus to cerebellum ratio and 3-cis-F-18 FCWAY had the best properties for measuring dynamic change in receptors, with lower affinity and faster pharmacokinetics. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.01.064
• 作为产物：
  描述：

  4-羟基环己烷甲酸乙酯 、 2,3,4,5,6-五甲基苄氯 在 吡啶 、 二乙胺基三氟化硫 、 氢氟酸 、 sodium hydroxide 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以410 mg的产率得到trans-pentamethylbenzyl 4-fluorocyclohexanecarboxylate
  参考文献：
  名称：

  Synthesis and in vivo biodistribution of F-18 labeled 3-cis-, 3-trans-, 4-cis-, and 4-trans-fluorocyclohexane derivatives of WAY 100635

  摘要：

  Radioligands that are specific for the serotonin 5-HT1A receptor will be useful in characterizing the physiological action of this receptor subtype. With radioligands of varying pharmacokinetic properties, investigators can measure not only receptor density, but also the effect of endogenous serotonin concentration. To this end, three additional fluorinated analogs of WAY 100635 were prepared and evaluated as 5-HT1A receptor ligands of varyin vertical bar%1e[OK]g pharmacokinetic properties based on our previous studies. These four compounds are cis-4-fluoro-, trans-4-fluoro-, cis-3-fluoro-, and trans-3-fluoro-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-(pyridin-2-yl)cyclohexanecarboxamides (FCWAYs). All four compounds were characterized and radiolabeled with fluorine-18, a 109.7 min half-life radionuclide used in positron emission tomography. We then determined in vitro inhibition constants at the 5-HT1A receptor; in vitro metabolic profile, using rat hepatocytes and liquid chromatography/mass spectroscopy (LC/MS); and the rate of defluorination and hippocampus to cerebellum ratio ex vivo. This led to the conclusion that high affinity 4-trans-F-18 FCWAY had the best properties for measuring receptor density given its high hippocampus to cerebellum ratio and 3-cis-F-18 FCWAY had the best properties for measuring dynamic change in receptors, with lower affinity and faster pharmacokinetics. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.01.064