5-bromo-N-[[(2S)-1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-3-methoxy-2-(111C)methoxybenzamide | 1045810-36-3

• 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: 5-bromo-N-[[(2S)-1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-3-methoxy-2-(111C)methoxybenzamide
• CAS: 1045810-36-3
• 化学式: C₁₈H₂₅BrN₂O₃
• 分子量: 396.301
• InChiKey: RQQHKEIJFYJFJI-SVGATJFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  50.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (S)-5-溴-N-[(1-环丙基甲基-2-吡咯烷基)甲基]-2-羟基-3-甲氧基苯甲酰胺 、 [11C]methyl triflate 在 sodium hydroxide 作用下， 以 丙酮 为溶剂， 生成 5-bromo-N-[[(2S)-1-(cyclopropylmethyl)pyrrolidin-2-yl]methyl]-3-methoxy-2-(111C)methoxybenzamide
  参考文献：
  名称：

  [11C]Cyclopropyl-FLB 457: A PET radioligand for low densities of dopamine D2 receptors

  摘要：

  (S)-5-Bromo- N-[(1-cyclopropylmethyl-2-pyrrolidinyl)methyl]-2,3-dimethoxybenzamide (4) has pico-molarin vitro binding affinity to D-2 receptor (K-i (D-2) = 0.003 nM) with lower affinity to D-3 receptor (K-i (D-3) = 0.22 nM). In this study, we describe radiosynthesis of [C-11]4 and evaluation of its binding characteristics in post-mortem human brain autoradiography and with PET in cynomolgus monkeys. The 11C labelled 4 was synthesized by using [C-11] methyltriflate in a methylation reaction with its phenolic precursor with good incorporation yield (64 +/- 11%, DCY) and high specific radioactivity > 370 GBq/mu mol (> 10 000 Ci/mmol). In post-mortem human brain autoradiography [C-11]4 exhibited high specific binding in brain regions enriched with dopamine D-2/D-3 receptors and low level of non-specific binding. In cynomolgus monkeys [C-11]4 exhibited high brain uptake reaching 4.4% ID at 7.5 min. The binding in the extrastriatal low density D-2-receptor regions; thalamus and frontal, parietal, temporal, and occipital cortex, was clearly visible. Pre-treatment with raclopride (1 mg/kg as tartrate) caused high reduction of binding in extrastriatal regions, including cerebellum. [C-11]4 is a promising radioligand for imaging D2 receptors in low density regions in brain. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.039

文献信息

• [11C]Cyclopropyl-FLB 457: A PET radioligand for low densities of dopamine D2 receptors
  作者：Anu J. Airaksinen、Sangram Nag、Sjoerd J. Finnema、Jogeshwar Mukherjee、Sankha Chattopadhyay、Balázs Gulyás、Lars Farde、Christer Halldin

  DOI：10.1016/j.bmc.2008.05.039

  日期：2008.7.1

  (S)-5-Bromo- N-[(1-cyclopropylmethyl-2-pyrrolidinyl)methyl]-2,3-dimethoxybenzamide (4) has pico-molarin vitro binding affinity to D-2 receptor (K-i (D-2) = 0.003 nM) with lower affinity to D-3 receptor (K-i (D-3) = 0.22 nM). In this study, we describe radiosynthesis of [C-11]4 and evaluation of its binding characteristics in post-mortem human brain autoradiography and with PET in cynomolgus monkeys. The 11C labelled 4 was synthesized by using [C-11] methyltriflate in a methylation reaction with its phenolic precursor with good incorporation yield (64 +/- 11%, DCY) and high specific radioactivity > 370 GBq/mu mol (> 10 000 Ci/mmol). In post-mortem human brain autoradiography [C-11]4 exhibited high specific binding in brain regions enriched with dopamine D-2/D-3 receptors and low level of non-specific binding. In cynomolgus monkeys [C-11]4 exhibited high brain uptake reaching 4.4% ID at 7.5 min. The binding in the extrastriatal low density D-2-receptor regions; thalamus and frontal, parietal, temporal, and occipital cortex, was clearly visible. Pre-treatment with raclopride (1 mg/kg as tartrate) caused high reduction of binding in extrastriatal regions, including cerebellum. [C-11]4 is a promising radioligand for imaging D2 receptors in low density regions in brain. (c) 2008 Elsevier Ltd. All rights reserved.