(-)-(1R,5S)-N-tert-butoxycarbonyl-9-(2-nitro-5-pyridyl)-1,2,3,4,5,6-hexahydro-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one | 660847-75-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 羽扇豆生物碱
• 英文名称: (-)-(1R,5S)-N-tert-butoxycarbonyl-9-(2-nitro-5-pyridyl)-1,2,3,4,5,6-hexahydro-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one
• 英文别名: (-)-N-tert-butoxycarbonyl-9-(2-nitro-5-pyridinyl)cytisine
• CAS: 660847-75-6
• 化学式: C₂₁H₂₄N₄O₅
• 分子量: 412.445
• InChiKey: QIIHBUKMPLVZPG-DZGCQCFKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.17
• 重原子数：
  30.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  107.57
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (-)-(1R,5S)-N-tert-butoxycarbonyl-9-(2-nitro-5-pyridyl)-1,2,3,4,5,6-hexahydro-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one 在 potassium [¹⁸F]fluoride 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 作用下， 以 二甲基亚砜 为溶剂， 反应 0.12h， 生成 (-)-(1R,5S)-N-tert-butoxycarbonyl-9-(2-[18F]fluoro-5-pyridyl)-1,2,3,4,5,6-hexahydro-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one
  参考文献：
  名称：

  Synthesis of a [2-Pyridinyl-18F]-labelled fluoro derivative of (−)-Cytisine as a candidate radioligand for brain nicotinic α4β2 receptor imaging with PET

  摘要：

  In recent years, there has been considerable effort to design and synthesize radiotracers suitable for use in Positron Emission Tomography (PET) imaging of the alpha4beta2 neuronal nicotinic acetylcholine receptor (nAChR) subtype. A new fluoropyridinyl derivative of (-)-cytisine (1), namely (-)-9-(2-fluoropyridinyl)cytisine (3, K-i values of 24 and 3462 nM for the alpha4beta2 and alpha7 nAChRs subtypes, respectively) has been synthesized in four chemical steps from (-)-cytisine and labelled with fluorine-18 (T-1/2: 119.8 min) using an efficient two-step radiochemical process [(a) nucleophilic heteroaromatic ortho-radiofluorination using the corresponding N-Boc-protected nitro-derivative, (b) TFA removal of the Boc protective group]. Typically, 20-45 mCi (0.74-1.67 GBq) of (-)-9-(2-[F-18]fluoropyridinyl)cytisine ([F-18]-3, 2-3 C-i/mumol or 74-111 GBq/pmol) were easily obtained in 70-75 min starting from a 100 mCi (3.7 GBq) aliquot of a cyclotron-produced [F-18]fluoride production batch (20-45% non decay-corrected yield based on the starting [F-18]fluoride). The in vivo pharmacological profile of (-)-9-(2-[F-18]fluoropyridinyl)cytisine ([F-18]-3) was evaluated in rats with biodistribution studies and brain radioactivity monitoring using intracerebral radiosensitive beta-microprobes. The observed in vivo distribution of the radiotracer in brain was rather uniform, and did not match with the known regional densities of nAChRs. It was also significantly different from that of the parent compound (-)-[H-3]cytisine. Moreover, competition studies with (-)-nicotine (5 mg/kg, 5 min before the radiotracer injection) did not reduce brain uptake of the radiotracer. These experiments clearly indicate that (-)-9-(2-[F-18]fluoropyridinyl)cytisine ([F-18]-3) does not have the required properties for imaging nAChRs using PET. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.09.042
• 作为产物：
  描述：

  N-Boc-cytisine 在 四(三苯基膦)钯 碘 、 silver sulfate 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 (-)-(1R,5S)-N-tert-butoxycarbonyl-9-(2-nitro-5-pyridyl)-1,2,3,4,5,6-hexahydro-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one
  参考文献：
  名称：

  Synthesis of a [2-Pyridinyl-18F]-labelled fluoro derivative of (−)-Cytisine as a candidate radioligand for brain nicotinic α4β2 receptor imaging with PET

  摘要：

  In recent years, there has been considerable effort to design and synthesize radiotracers suitable for use in Positron Emission Tomography (PET) imaging of the alpha4beta2 neuronal nicotinic acetylcholine receptor (nAChR) subtype. A new fluoropyridinyl derivative of (-)-cytisine (1), namely (-)-9-(2-fluoropyridinyl)cytisine (3, K-i values of 24 and 3462 nM for the alpha4beta2 and alpha7 nAChRs subtypes, respectively) has been synthesized in four chemical steps from (-)-cytisine and labelled with fluorine-18 (T-1/2: 119.8 min) using an efficient two-step radiochemical process [(a) nucleophilic heteroaromatic ortho-radiofluorination using the corresponding N-Boc-protected nitro-derivative, (b) TFA removal of the Boc protective group]. Typically, 20-45 mCi (0.74-1.67 GBq) of (-)-9-(2-[F-18]fluoropyridinyl)cytisine ([F-18]-3, 2-3 C-i/mumol or 74-111 GBq/pmol) were easily obtained in 70-75 min starting from a 100 mCi (3.7 GBq) aliquot of a cyclotron-produced [F-18]fluoride production batch (20-45% non decay-corrected yield based on the starting [F-18]fluoride). The in vivo pharmacological profile of (-)-9-(2-[F-18]fluoropyridinyl)cytisine ([F-18]-3) was evaluated in rats with biodistribution studies and brain radioactivity monitoring using intracerebral radiosensitive beta-microprobes. The observed in vivo distribution of the radiotracer in brain was rather uniform, and did not match with the known regional densities of nAChRs. It was also significantly different from that of the parent compound (-)-[H-3]cytisine. Moreover, competition studies with (-)-nicotine (5 mg/kg, 5 min before the radiotracer injection) did not reduce brain uptake of the radiotracer. These experiments clearly indicate that (-)-9-(2-[F-18]fluoropyridinyl)cytisine ([F-18]-3) does not have the required properties for imaging nAChRs using PET. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.09.042

文献信息

• Roger, G.; Lagnel, B.; Rouden, J., Journal of labelled compounds and radiopharmaceuticals, 2003, vol. 46, p. S138 - S138
  作者：Roger, G.、Lagnel, B.、Rouden, J.、Besret, L.、Valette, H.、Demphel, S.、Coulon, C.、Ottaviani, M.、Wrenn, L.、Letchworth, S.、Bohme, G. A.、et al.

  DOI：——

  日期：——