S-(+)-ethyl α-hydroxy-α-phenyl-α-(1-tosylpenta-5-yl) acetate | 212627-51-5

• 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: S-(+)-ethyl α-hydroxy-α-phenyl-α-(1-tosylpenta-5-yl) acetate
• 英文别名: ethyl (2S)-2-hydroxy-7-(4-methylphenyl)sulfonyloxy-2-phenylheptanoate
• CAS: 212627-51-5
• 化学式: C₂₂H₂₈O₆S
• 分子量: 420.527
• InChiKey: SVOAWQZMGOVJBK-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  98.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  S-(+)-ethyl α-hydroxy-α-phenyl-α-(1-tosylpenta-5-yl) acetate 在 四丁基氟化铵 、 sodium 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 3.0h， 生成 S-(+)-1-azabicyclo[2.2.2]oct-3-yl S-(+)-α-(1-fluoropent-5-yl)-α-hydroxy-α-phenylacetate
  参考文献：
  名称：

  Resolution, in vitro and in vivo evaluation of fluorine-18-labeled isomers of 1-azabicyclo[2.2.2]oct-3-ylα-(1-fluoropent-5-yl)α-hydroxy-α-phenylacetate (FQNPe) as new PET candidates for the imaging of muscarinic-cholinergic receptor

  摘要：

  l-Azabicyclo[2.2.2]oct-3-yl alpha-(1-fluoropent-5-yl)-alpha-hydroxy-alpha-phenylacetate (FQNPe, 2), an analogue of 1-azabicyclo[2.2.2]oct-3-yl alpha,alpha-(diphenyl)-alpha-hydroxyacetate (QNB), was resolved into its four stereoisomers. In vitro binding assays of the stereoisomers of 2 demonstrated that while the (S,S)-isomer did not have significant receptor binding, the other stereoisomers of 2 bound with high affinity to the various mAChR subtypes [K-i, nM: m1, (R,R), 0.33; (R,S), 1.4; (S,R), 3.8; m2, (R,R), 0.1; (R,S), 4.2; (S,R), < 75% binding; m3, (R,R), 0.34; (R,S), 3.1; (S,R), 7.6]. The (R,R)- and (R,S)stereoisomers of 2 were radiolabeled with fluorine-18 via a two step procedure in radiochemical yields of 12-21% (n=2) and 9% (decayed corrected to beginning of synthesis), respectively. In vivo biodistribution studies demonstrated significant uptake of [F-18]-(R,R)-2 in cerebral mAChR-rich regions of rat brains up to 3 h post injection. Low accumulation of fluorine-18 in the bone indicated that [F-18]-(R,R)-2 displayed significant in vivo stability. In contrast. [F-18]-(R,S)-2 demonstrated rapid washout from all cerebral regions. Preinjection of (R)-QNB (3 mg/kg) 1 h prior to the injection of [F-18]-(R,R)-2 blocked the uptake of activity in cerebral regions by approximately 90% while the preinjection of haloperidol (3 mg/kg) 1 h prior to the injection of [F-18]-(R;R)2 demonstrated no statistically significant effect on the binding of the radiotracer. An ex vivo metabolic study utilizing [F-18]-(R,R)-2 demonstrated that greater than 96% of the organic soluble radioactivity which localized in the brain and heart at 1 h post-injection migrated on TLC with the same mobility as the parent. Although [F-18]-(R,R)-2 did not demonstrate a desired in vitro or in vivo mAChR subtype selectivity, these results suggest that the introduction of a fluoroalkyl group in various benzylic analogues of QNB is an attractive radiolabeling moiety for further evaluation in the design of selective PET mAChR imaging ligands.

  DOI：

  10.1002/(sici)1099-1344(1998080)41:8<681::aid-jlcr131>3.0.co;2-q
• 作为产物：
  描述：

  S-(+)-ethyl α-(1-chloropent-5-yl)-α-hydroxy-α-phenylacetate 在 sodium iodide 作用下， 以 丙酮 、 乙腈 为溶剂， 反应 76.0h， 生成 S-(+)-ethyl α-hydroxy-α-phenyl-α-(1-tosylpenta-5-yl) acetate
  参考文献：
  名称：

  Resolution, in vitro and in vivo evaluation of fluorine-18-labeled isomers of 1-azabicyclo[2.2.2]oct-3-ylα-(1-fluoropent-5-yl)α-hydroxy-α-phenylacetate (FQNPe) as new PET candidates for the imaging of muscarinic-cholinergic receptor

  摘要：

  l-Azabicyclo[2.2.2]oct-3-yl alpha-(1-fluoropent-5-yl)-alpha-hydroxy-alpha-phenylacetate (FQNPe, 2), an analogue of 1-azabicyclo[2.2.2]oct-3-yl alpha,alpha-(diphenyl)-alpha-hydroxyacetate (QNB), was resolved into its four stereoisomers. In vitro binding assays of the stereoisomers of 2 demonstrated that while the (S,S)-isomer did not have significant receptor binding, the other stereoisomers of 2 bound with high affinity to the various mAChR subtypes [K-i, nM: m1, (R,R), 0.33; (R,S), 1.4; (S,R), 3.8; m2, (R,R), 0.1; (R,S), 4.2; (S,R), < 75% binding; m3, (R,R), 0.34; (R,S), 3.1; (S,R), 7.6]. The (R,R)- and (R,S)stereoisomers of 2 were radiolabeled with fluorine-18 via a two step procedure in radiochemical yields of 12-21% (n=2) and 9% (decayed corrected to beginning of synthesis), respectively. In vivo biodistribution studies demonstrated significant uptake of [F-18]-(R,R)-2 in cerebral mAChR-rich regions of rat brains up to 3 h post injection. Low accumulation of fluorine-18 in the bone indicated that [F-18]-(R,R)-2 displayed significant in vivo stability. In contrast. [F-18]-(R,S)-2 demonstrated rapid washout from all cerebral regions. Preinjection of (R)-QNB (3 mg/kg) 1 h prior to the injection of [F-18]-(R,R)-2 blocked the uptake of activity in cerebral regions by approximately 90% while the preinjection of haloperidol (3 mg/kg) 1 h prior to the injection of [F-18]-(R;R)2 demonstrated no statistically significant effect on the binding of the radiotracer. An ex vivo metabolic study utilizing [F-18]-(R,R)-2 demonstrated that greater than 96% of the organic soluble radioactivity which localized in the brain and heart at 1 h post-injection migrated on TLC with the same mobility as the parent. Although [F-18]-(R,R)-2 did not demonstrate a desired in vitro or in vivo mAChR subtype selectivity, these results suggest that the introduction of a fluoroalkyl group in various benzylic analogues of QNB is an attractive radiolabeling moiety for further evaluation in the design of selective PET mAChR imaging ligands.

  DOI：

  10.1002/(sici)1099-1344(1998080)41:8<681::aid-jlcr131>3.0.co;2-q

文献信息

• Resolution, in vitro and in vivo evaluation of fluorine-18-labeled isomers of 1-azabicyclo[2.2.2]oct-3-ylα-(1-fluoropent-5-yl)α-hydroxy-α-phenylacetate (FQNPe) as new PET candidates for the imaging of muscarinic-cholinergic receptor
  作者：H. Luo、A. L. Beets、M. J. McAllister、M. Greenbaum、D. W. McPherson、F. F. Knapp

  DOI：10.1002/(sici)1099-1344(1998080)41:8<681::aid-jlcr131>3.0.co;2-q

  日期：1998.8

  l-Azabicyclo[2.2.2]oct-3-yl alpha-(1-fluoropent-5-yl)-alpha-hydroxy-alpha-phenylacetate (FQNPe, 2), an analogue of 1-azabicyclo[2.2.2]oct-3-yl alpha,alpha-(diphenyl)-alpha-hydroxyacetate (QNB), was resolved into its four stereoisomers. In vitro binding assays of the stereoisomers of 2 demonstrated that while the (S,S)-isomer did not have significant receptor binding, the other stereoisomers of 2 bound with high affinity to the various mAChR subtypes [K-i, nM: m1, (R,R), 0.33; (R,S), 1.4; (S,R), 3.8; m2, (R,R), 0.1; (R,S), 4.2; (S,R), < 75% binding; m3, (R,R), 0.34; (R,S), 3.1; (S,R), 7.6]. The (R,R)- and (R,S)stereoisomers of 2 were radiolabeled with fluorine-18 via a two step procedure in radiochemical yields of 12-21% (n=2) and 9% (decayed corrected to beginning of synthesis), respectively. In vivo biodistribution studies demonstrated significant uptake of [F-18]-(R,R)-2 in cerebral mAChR-rich regions of rat brains up to 3 h post injection. Low accumulation of fluorine-18 in the bone indicated that [F-18]-(R,R)-2 displayed significant in vivo stability. In contrast. [F-18]-(R,S)-2 demonstrated rapid washout from all cerebral regions. Preinjection of (R)-QNB (3 mg/kg) 1 h prior to the injection of [F-18]-(R,R)-2 blocked the uptake of activity in cerebral regions by approximately 90% while the preinjection of haloperidol (3 mg/kg) 1 h prior to the injection of [F-18]-(R;R)2 demonstrated no statistically significant effect on the binding of the radiotracer. An ex vivo metabolic study utilizing [F-18]-(R,R)-2 demonstrated that greater than 96% of the organic soluble radioactivity which localized in the brain and heart at 1 h post-injection migrated on TLC with the same mobility as the parent. Although [F-18]-(R,R)-2 did not demonstrate a desired in vitro or in vivo mAChR subtype selectivity, these results suggest that the introduction of a fluoroalkyl group in various benzylic analogues of QNB is an attractive radiolabeling moiety for further evaluation in the design of selective PET mAChR imaging ligands.