cis-pentamethylbenzyl 4-<(4-nitrobenzenesulfonyl)oxy>cyclohexanecarboxylate | 223699-71-6

• 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: cis-pentamethylbenzyl 4-<(4-nitrobenzenesulfonyl)oxy>cyclohexanecarboxylate
• CAS: 223699-71-6
• 化学式: C₂₅H₃₁NO₇S
• 分子量: 489.59
• InChiKey: LFFKITSXLBYJDE-GRGXKFILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.14
• 重原子数：
  34.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  112.81
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  cis-pentamethylbenzyl 4-<(4-nitrobenzenesulfonyl)oxy>cyclohexanecarboxylate 在 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 、 氢氟酸 作用下， 以 丙酮 为溶剂， 反应 0.17h， 生成
  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：

  2,3,4,5,6-五甲基苄氯 在 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 cis-pentamethylbenzyl 4-<(4-nitrobenzenesulfonyl)oxy>cyclohexanecarboxylate
  参考文献：
  名称：

  Development of Fluorine-18-Labeled 5-HT_1A Antagonists

  摘要：

  We have synthesized five fluorinated derivatives of WAY 100635, N-{2-[4-(2-methoxyphenyl)piperazino]ethyl)-N-(2-pyridyl)cyclohexanecarboxamide (4a), using various acids in place of the cyclohexanecarboxylic acid (CHCA, 2a) in the reaction scheme. The five acids are 4-fluorobenzoic acid (FB, 2b), 4-fluoro-3-methylbenzoic acid (MeFB, 2c), trans-4-fluorocyclohexanecarboxylic acid (FC, 2d), 4-(fluoromethyl)benzoic acid (FMeB, 2e), and 3-nitro-4-(fluoromethyl)benzoic acid (NFMeB, 2f) (see Scheme 1). These compounds were radiolabeled with fluorine-18, and their biological properties were evaluated in rats and compared with those of [C-11]carbonyl WAY 100635 ([carbonyl-C-11]4a), [Carbonyl-C-11]4a cleared the brain with a biological half-life averaging 41 min. The metabolite-corrected blood radioactivity had a half-life of 29 min. [F-18]FCWAY ([F-18]4d) gave half-lives and intercepts comparable to [carbonyl-C-11]4a in the brain, but the blood clearance was faster. [F-18]FBWAY ([F-18]4b) showed an early rapid net efflux from the whole brain, clearing with a biological half-life of 35 min. The metabolite-corrected blood half-life was 41 min. The comparable whole brain and blood half-lives for Me[F-18]FBWAY ([F-18]4c) were 16 and 18 min, respectively. For each compound, the corresponding carboxylic acid was identified as a major metabolite in blood. Fluoride was also found after injection of [F-18]4d. However, for all compounds there was a good correlation (R > 0.97) between the differential uptake ratio (DUR, (%ID/g) x body weight (g)/100) in individual rat brain regions at 30 min after injection and the concentration of receptors as determined by in vitro quantitative autoradiography in rat. Specific binding ratios [region of interest (ROI)/ cerebellum-1] in control studies for cortex (Ctx) and hippocampus (H) were higher for [carbonyl-C-11]4a and [F-18]4d compared to [F-18]4b and [F-18]4c. [F-18]4d has similar pharmacokinetic properties and comparable specific binding ratios to [carbonyl-11C]4a. Fifty nanomoles of 4a blocked only 30% of the specific binding of [F-18]4d, while complete blockade was obtained from co-injection of 200 nmol of 4a (H/Cb-1 from 17.2 to 0.6). [F-18]4b and [F-18]4c showed lower specific binding ratios than [carbonyl-C-11]4a and [F-18]4d. [F-18]4c was superior to [F-18]4b since its specific binding was more readily blocked by 4a. These studies suggest that [F-18]4c should be a useful compound to assess dynamic changes in serotonin levels while [F-18]4d, with its high contrast and F-18 label, should provide better statistics and quantification for static measurement of 5-HT1A receptor distribution.

  DOI：

  10.1021/jm980456f