tert-butyl 3-fluoromethyl-4-phenylquinoline-2-carboxylate | 893404-65-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: tert-butyl 3-fluoromethyl-4-phenylquinoline-2-carboxylate
• CAS: 893404-65-4
• 化学式: C₂₁H₂₀FNO₂
• 分子量: 337.394
• InChiKey: BHSHIPFCEGZMJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.33
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  39.19
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-fluoromethyl-4-phenylquinoline-2-carboxylate 在 甲酸 、 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 23.17h， 生成 3-fluoromethyl-4-phenyl-N-(phenylmethyl)quinoline-2-carboxamide
  参考文献：
  名称：

  Synthesis, labeling, and biological evaluation of halogenated 2-quinolinecarboxamides as potential radioligands for the visualization of peripheral benzodiazepine receptors

  摘要：

  The previous exploration of the structure-affinity relationships concerning 4-phenyl-2-quinolinecarboxamide peripheral benzodiazepine receptor (PBR) ligands 6 showed as an interesting result the importance of the presence of a chlorine atom in the methylene carbon at position 3 of the quinoline nucleus. The subnanomolar PBR affinity shown by N-benzyl-3-chloromethyl-N-methyl-4-phenyl-2-quinolinecarboxamide (6b) suggested its chlorine atom to be replaced with other halogens in order to optimize the interaction of the quinolinecarboxamide derivatives with PBR and to develop suitable candidates for positron emission tomography (PET) or single photon emission computed tomography (SPECT) studies. The binding studies led to the discovery of fluoromethyl derivative 6a, which showed an IC50 value of 0.11 nM and is, therefore, one of the most potent PBR ligands so far described. Fluoromethyl derivative 6a has been labeled with C-11 (t(1/2) = 20.4 min, beta(+) = 99.8%) starting from the corresponding des-methyl precursor (14) using [C-11]CH3I in the presence of tetrabutylammonium hydroxide in DMF with a 35-40% radiochemical yield (corrected for decay) and 1.5 Ci/mu mol of specific radioactivity. Ex vivo rat biodistribution and inhibition (following intravenous pre-administration of PK11195) studies showed that [C-11]6a rapidly and specifically accumulated in PBR-rich tissues such as heart, lung, kidney, spleen, and adrenal, and at a lower level in other peripheral organs and in the brain. The images obtained in mouse with small animal YAP-(S)PET essentially confirmed the result of the ex vivo biodistribution experiments. The biological data suggest that [C-11]6a is a promising radioligand for peripheral benzodiazepine receptor PET imaging in vivo. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.02.004
• 作为产物：
  描述：

  3-methyl-4-phenylquinoline-2-carboxylic acid 在 potassium fluoride 、 N-溴代丁二酰亚胺(NBS) 、 氯化亚砜 、 18-冠醚-6 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 四氯化碳 、 二氯甲烷 、 乙腈 为溶剂， 反应 20.0h， 生成 tert-butyl 3-fluoromethyl-4-phenylquinoline-2-carboxylate
  参考文献：
  名称：

  Synthesis, labeling, and biological evaluation of halogenated 2-quinolinecarboxamides as potential radioligands for the visualization of peripheral benzodiazepine receptors

  摘要：

  The previous exploration of the structure-affinity relationships concerning 4-phenyl-2-quinolinecarboxamide peripheral benzodiazepine receptor (PBR) ligands 6 showed as an interesting result the importance of the presence of a chlorine atom in the methylene carbon at position 3 of the quinoline nucleus. The subnanomolar PBR affinity shown by N-benzyl-3-chloromethyl-N-methyl-4-phenyl-2-quinolinecarboxamide (6b) suggested its chlorine atom to be replaced with other halogens in order to optimize the interaction of the quinolinecarboxamide derivatives with PBR and to develop suitable candidates for positron emission tomography (PET) or single photon emission computed tomography (SPECT) studies. The binding studies led to the discovery of fluoromethyl derivative 6a, which showed an IC50 value of 0.11 nM and is, therefore, one of the most potent PBR ligands so far described. Fluoromethyl derivative 6a has been labeled with C-11 (t(1/2) = 20.4 min, beta(+) = 99.8%) starting from the corresponding des-methyl precursor (14) using [C-11]CH3I in the presence of tetrabutylammonium hydroxide in DMF with a 35-40% radiochemical yield (corrected for decay) and 1.5 Ci/mu mol of specific radioactivity. Ex vivo rat biodistribution and inhibition (following intravenous pre-administration of PK11195) studies showed that [C-11]6a rapidly and specifically accumulated in PBR-rich tissues such as heart, lung, kidney, spleen, and adrenal, and at a lower level in other peripheral organs and in the brain. The images obtained in mouse with small animal YAP-(S)PET essentially confirmed the result of the ex vivo biodistribution experiments. The biological data suggest that [C-11]6a is a promising radioligand for peripheral benzodiazepine receptor PET imaging in vivo. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.02.004