2-[(2-chlorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno-[2,3-c]pyran-7,4'-piperidine]-1'-yl)propanoic acid | 1283095-55-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 2-[(2-chlorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno-[2,3-c]pyran-7,4'-piperidine]-1'-yl)propanoic acid
• 英文别名: 2-[(2-Chlorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)propanoic acid
• CAS: 1283095-55-5
• 化学式: C₂₁H₂₃ClFNO₃S
• 分子量: 423.936
• InChiKey: DZXHXIGTKALJDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  78
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[(2-chlorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno-[2,3-c]pyran-7,4'-piperidine]-1'-yl)propanoic acid 、 盐酸甲胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以75%的产率得到2-[(2-chlorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno-[2,3-c]pyran-7,4'-piperidine]-1'-yl)-N-methylpropanamide
  参考文献：
  名称：

  Synthesis and Evaluation of Radioligands for Imaging Brain Nociceptin/Orphanin FQ Peptide (NOP) Receptors with Positron Emission Tomography

  摘要：

  Positron emission tomography (PET) coupled to an effective radioligand could provide an important tool for understanding possible links between neuropsychiatric disorders and brain NOP (nociceptin/orphanin FQ peptide) receptors. We sought to develop such a PET radioligand. High-affinity NOP ligands were synthesized based on a 3-(2'-fluoro-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran]-1-yl)-2(2-halobenzyl)-N-alkylpropanamide scaffold and from experimental screens in rats, with ex vivo LC-MS/MS measures, three ligands were identified for labeling with carbon-11 and evaluation with PET in monkey. Each ligand was labeled by C-11-methylation of an N-desmethyl precursor and studied in monkey under baseline and NOP receptor-preblock conditions. The three radioligands, [C-11] (S) 10a-c, gave similar results. Baseline scans showed high entry of radioactivity into the brain to give a distribution reflecting that expected for NOP receptors. Preblock experiments showed high early peak levels of brain radioactivity, which rapidly declined to a Much lower level than seen in baseline scans, thereby indicating a high level of receptor-specific binding in baseline experiments. Overall, [C-11](S)-10c showed the most favorable receptor-specific signal and kinetics and is now selected for evaluation in human subjects.

  DOI：

  10.1021/jm101487v
• 作为产物：
  描述：

  4',5'-二氢-螺[哌啶-4,7'-[7H]噻吩并[2,3-c]吡喃]-1-羧酸叔丁酯 在 盐酸 、 正丁基锂 、 三乙胺 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 二氯甲烷 为溶剂， 反应 32.0h， 生成 2-[(2-chlorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno-[2,3-c]pyran-7,4'-piperidine]-1'-yl)propanoic acid
  参考文献：
  名称：

  Synthesis and Evaluation of Radioligands for Imaging Brain Nociceptin/Orphanin FQ Peptide (NOP) Receptors with Positron Emission Tomography

  摘要：

  Positron emission tomography (PET) coupled to an effective radioligand could provide an important tool for understanding possible links between neuropsychiatric disorders and brain NOP (nociceptin/orphanin FQ peptide) receptors. We sought to develop such a PET radioligand. High-affinity NOP ligands were synthesized based on a 3-(2'-fluoro-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran]-1-yl)-2(2-halobenzyl)-N-alkylpropanamide scaffold and from experimental screens in rats, with ex vivo LC-MS/MS measures, three ligands were identified for labeling with carbon-11 and evaluation with PET in monkey. Each ligand was labeled by C-11-methylation of an N-desmethyl precursor and studied in monkey under baseline and NOP receptor-preblock conditions. The three radioligands, [C-11] (S) 10a-c, gave similar results. Baseline scans showed high entry of radioactivity into the brain to give a distribution reflecting that expected for NOP receptors. Preblock experiments showed high early peak levels of brain radioactivity, which rapidly declined to a Much lower level than seen in baseline scans, thereby indicating a high level of receptor-specific binding in baseline experiments. Overall, [C-11](S)-10c showed the most favorable receptor-specific signal and kinetics and is now selected for evaluation in human subjects.

  DOI：

  10.1021/jm101487v