Hydroxy-diphenyl-acetic acid (R)-piperidin-3-yl ester | 315680-05-8

• 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: Hydroxy-diphenyl-acetic acid (R)-piperidin-3-yl ester
• 英文别名: [(3R)-piperidin-3-yl] 2-hydroxy-2,2-diphenylacetate
• CAS: 315680-05-8
• 化学式: C₁₉H₂₁NO₃
• 分子量: 311.381
• InChiKey: IGXOSKVDCFQEBF-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-溴-3-氟丙烷 、 Hydroxy-diphenyl-acetic acid (R)-piperidin-3-yl ester 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以73%的产率得到Hydroxy-diphenyl-acetic acid (R)-1-(3-fluoro-propyl)-piperidin-3-yl ester
  参考文献：
  名称：

  Synthesis, ¹⁸F-Labeling, and Biological Evaluation of Piperidyl and Pyrrolidyl Benzilates as in Vivo Ligands for Muscarinic Acetylcholine Receptors

  摘要：

  A series of 31 compounds based on the piperidyl or pyrrolidyl benzilate scaffold were prepared from methyl benzilate and 4-piperidinol, (R)-(+)-3-piperidinol, or (R)-(+)-3-pyrrolidinol. Amine substituents included alkyl and aralkyl groups. In vitro K-i values ranged from 0.05 nM to > 100 nM. (R)-N-( 2-Fluoroethyl)-3-piperidyl benzilate (3-FEPB, 22, K-i = 12.1 nM) and N-(2-fluoroethyl)-4-piperidyl benzilate (4-FEPB, 8, K-i = 1.83 nM) were selected for radiolabeling with fluorine-18. Using alkylation with 2-[F-18]fluoroethyl triflate, 3-[F-18]FEPB (42) and 4-[F-18]-FEPB (43) were produced in 7-9% radiochemical yield and >97% radiochemical purity. For in vivo studies, retention was moderate in mouse brain for 42; however, blocking with scopolamine showed that uptake was not muscarinic cholinergic receptor-mediated. Conversely, 43 exhibited high, receptor-mediated retention in mouse brain, with significant; clearance after 1 h. These results suggest that 43 could have applications as an in vivo probe for measuring endogenous acetylcholine levels.

  DOI：

  10.1021/jm000305o
• 作为产物：
  描述：

  二苯乙醇酸甲酯 在 10percent Pd/C 高氯酸 、 氢气 、 sodium 作用下， 以 乙醇 、 苯 为溶剂， 反应 26.5h， 生成 Hydroxy-diphenyl-acetic acid (R)-piperidin-3-yl ester
  参考文献：
  名称：

  Synthesis, ¹⁸F-Labeling, and Biological Evaluation of Piperidyl and Pyrrolidyl Benzilates as in Vivo Ligands for Muscarinic Acetylcholine Receptors

  摘要：

  A series of 31 compounds based on the piperidyl or pyrrolidyl benzilate scaffold were prepared from methyl benzilate and 4-piperidinol, (R)-(+)-3-piperidinol, or (R)-(+)-3-pyrrolidinol. Amine substituents included alkyl and aralkyl groups. In vitro K-i values ranged from 0.05 nM to > 100 nM. (R)-N-( 2-Fluoroethyl)-3-piperidyl benzilate (3-FEPB, 22, K-i = 12.1 nM) and N-(2-fluoroethyl)-4-piperidyl benzilate (4-FEPB, 8, K-i = 1.83 nM) were selected for radiolabeling with fluorine-18. Using alkylation with 2-[F-18]fluoroethyl triflate, 3-[F-18]FEPB (42) and 4-[F-18]-FEPB (43) were produced in 7-9% radiochemical yield and >97% radiochemical purity. For in vivo studies, retention was moderate in mouse brain for 42; however, blocking with scopolamine showed that uptake was not muscarinic cholinergic receptor-mediated. Conversely, 43 exhibited high, receptor-mediated retention in mouse brain, with significant; clearance after 1 h. These results suggest that 43 could have applications as an in vivo probe for measuring endogenous acetylcholine levels.

  DOI：

  10.1021/jm000305o

文献信息

• Synthesis, ¹⁸F-Labeling, and Biological Evaluation of Piperidyl and Pyrrolidyl Benzilates as in Vivo Ligands for Muscarinic Acetylcholine Receptors
  作者：Marc B. Skaddan、Michael R. Kilbourn、Scott E. Snyder、Phil S. Sherman、Tim J. Desmond、Kirk A. Frey

  DOI：10.1021/jm000305o

  日期：2000.11.1

  A series of 31 compounds based on the piperidyl or pyrrolidyl benzilate scaffold were prepared from methyl benzilate and 4-piperidinol, (R)-(+)-3-piperidinol, or (R)-(+)-3-pyrrolidinol. Amine substituents included alkyl and aralkyl groups. In vitro K-i values ranged from 0.05 nM to > 100 nM. (R)-N-( 2-Fluoroethyl)-3-piperidyl benzilate (3-FEPB, 22, K-i = 12.1 nM) and N-(2-fluoroethyl)-4-piperidyl benzilate (4-FEPB, 8, K-i = 1.83 nM) were selected for radiolabeling with fluorine-18. Using alkylation with 2-[F-18]fluoroethyl triflate, 3-[F-18]FEPB (42) and 4-[F-18]-FEPB (43) were produced in 7-9% radiochemical yield and >97% radiochemical purity. For in vivo studies, retention was moderate in mouse brain for 42; however, blocking with scopolamine showed that uptake was not muscarinic cholinergic receptor-mediated. Conversely, 43 exhibited high, receptor-mediated retention in mouse brain, with significant; clearance after 1 h. These results suggest that 43 could have applications as an in vivo probe for measuring endogenous acetylcholine levels.