2-nitro-3-<2(S)-N-(tert-butoxycarbonyl)-2-azetidinylmethoxy>pyridine | 209530-92-7

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 2-nitro-3-<2(S)-N-(tert-butoxycarbonyl)-2-azetidinylmethoxy>pyridine
• 英文别名: 1-Azetidinecarboxylic acid, 2-[[[2-nitro-3-pyridinyl]oxy]methyl]-, 1,1-dimethylethyl ester, (2S)-；tert-butyl (2S)-2-[(2-nitropyridin-3-yl)oxymethyl]azetidine-1-carboxylate
• CAS: 209530-92-7
• 化学式: C₁₄H₁₉N₃O₅
• 分子量: 309.322
• InChiKey: PGOXRCXMJUXGQA-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  97.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-nitro-3-<2(S)-N-(tert-butoxycarbonyl)-2-azetidinylmethoxy>pyridine 在 <18F>FK-K₂₂₂-complex 作用下， 以 二甲基亚砜 为溶剂， 反应 0.02h， 生成 2-<18F>fluoro-3-<2(S)-(tert-butoxycarbonyl)-2-azetidinylmethoxy>pyridine
  参考文献：
  名称：

  Synthesis of 2-[18F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine, a highly potent radioligand for in vivo imaging central nicotinic acetylcholine receptors

  摘要：

  This paper reports the synthesis of 2-fluoro-3-[2(S)-2-azetidinylmethoxyl] and its radiolabeling with fluorine-18 ([F-18]FK-K-222) by nucleophilic aromatic nitro-to-fluoro substitution in DMSO by conventional heating at 150 degrees C for 20 min or by microwave activation at 100 Watt For 1 min. This fluoro compound is a closely related analog of the high affinity nicotinic ligand A-85380 (3-[2(S)-2-azetidinylmethoxy]pyridine) This compound is the lead compound of a novel 3-pyridyl ether series sf new nAChR ligands recently published, and possesses not only subnanomolar affinity, comparable to that of epibatidine, for the alpha 4 beta 2 subtype, but also a weaker affinity for the other subtypes of nAChRs. 110-140 mCi (4. -5.2 GBq) of pure 2-[F-18]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine ([F-18]fluoro-A-85380) could be obtained in less than 2 !lours, with specific radioactivities of 3-5 Ci/mu mol (111-185 GBq/mu mol) calculated for End of Bombardment (or 1.5-2.5 Ci/mu mol (55.5-92.5 GBq/mu mol) at End of Synthesis) for a 20 mu A, 30 min (36000 mu C) irradiation of a 95% enriched [O-18]water target with a 16 MeV proton beam [O-18(p,n)F-18]. Yields (with respect to [F-18]fluoride ion) : decay-corrected 49-64%; non-decay-corrected 25-33%. Total synthesis rime from EOB : 105-110 min (this includes the recovery of the [F-18]fluoride ion from the target and the [F-18]FK-K-222-complex preparation). Preliminary results in rats showed a substantial uptake of the ligand in the thalamus (1% I.D./g tissue at 30 min) while the cerebellar uptake was 2-fold lower. Thalamic uptake was reduced by 75-85% following a pretreatment with nicotine, cytisine, epibatidine or fluoro-A-85380. The full pharmacological profile and the potential for eventual clinical applications of this ligand as a tracer for PET experiments are currently under investigation.

  DOI：

  10.1002/(sici)1099-1344(199805)41:5<451::aid-jlcr111>3.0.co;2-r
• 作为产物：
  描述：

  1-Boc-L-吖啶-2-羧酸 在 dimethyl sulfide borane 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 生成 2-nitro-3-<2(S)-N-(tert-butoxycarbonyl)-2-azetidinylmethoxy>pyridine
  参考文献：
  名称：

  2-氟-3- [2（S）-2-氮杂环丁烷基甲氧基]吡啶的合成及其烟碱乙酰胆碱受体的体内结合性质：烟碱受体的一种新的正电子发射断层成像配体。

  摘要：

  一系列新的3-吡啶基醚的先导化合物氮杂环丁烷衍生物A-85380（3-[（（S）-2-azetidinylmethoxymethoxy] pyrididine））是人类alpha4beta2烟碱乙酰胆碱受体（nAChR）的有效和选择性配体亚型。在体外，A-85380的氟衍生物（2-氟-3-[（S）-2-氮杂环丁烷基甲氧基]吡啶或FA-85380）竞争取代[3H]胱氨酸或[3H]表巴替丁，Ki值分别为48和46 pM。FA-85380已由正电子发射极氟18（t1 / 2（半衰期）= 110分钟）标记，且无载体的亲核芳族取代被具有[3- [2]的K [18F] F-K222络合物取代（S）-N-（叔丁氧基羰基）-2-氮杂环丁烷基甲氧基]吡啶-2-基）三甲基铵三氟甲磺酸盐作为高效标记前体，然后用TFA去除Boc保护基。自回旋加速器氟18生产（EOB）结束以来，总合成时间为50-53分钟。相对于最

  DOI：

  10.1021/jm9910223

文献信息

• Synthesis of 2-[18F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine, a highly potent radioligand for in vivo imaging central nicotinic acetylcholine receptors
  作者：Frédéric Dolle、Héric Valette、Michel Bottlaender、Françoise Hinnen、Françoise Vaufrey、Ilonka Guenther、Christian Crouzel

  DOI：10.1002/(sici)1099-1344(199805)41:5<451::aid-jlcr111>3.0.co;2-r

  日期：1998.5

  This paper reports the synthesis of 2-fluoro-3-[2(S)-2-azetidinylmethoxyl] and its radiolabeling with fluorine-18 ([F-18]FK-K-222) by nucleophilic aromatic nitro-to-fluoro substitution in DMSO by conventional heating at 150 degrees C for 20 min or by microwave activation at 100 Watt For 1 min. This fluoro compound is a closely related analog of the high affinity nicotinic ligand A-85380 (3-[2(S)-2-azetidinylmethoxy]pyridine) This compound is the lead compound of a novel 3-pyridyl ether series sf new nAChR ligands recently published, and possesses not only subnanomolar affinity, comparable to that of epibatidine, for the alpha 4 beta 2 subtype, but also a weaker affinity for the other subtypes of nAChRs. 110-140 mCi (4. -5.2 GBq) of pure 2-[F-18]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine ([F-18]fluoro-A-85380) could be obtained in less than 2 !lours, with specific radioactivities of 3-5 Ci/mu mol (111-185 GBq/mu mol) calculated for End of Bombardment (or 1.5-2.5 Ci/mu mol (55.5-92.5 GBq/mu mol) at End of Synthesis) for a 20 mu A, 30 min (36000 mu C) irradiation of a 95% enriched [O-18]water target with a 16 MeV proton beam [O-18(p,n)F-18]. Yields (with respect to [F-18]fluoride ion) : decay-corrected 49-64%; non-decay-corrected 25-33%. Total synthesis rime from EOB : 105-110 min (this includes the recovery of the [F-18]fluoride ion from the target and the [F-18]FK-K-222-complex preparation). Preliminary results in rats showed a substantial uptake of the ligand in the thalamus (1% I.D./g tissue at 30 min) while the cerebellar uptake was 2-fold lower. Thalamic uptake was reduced by 75-85% following a pretreatment with nicotine, cytisine, epibatidine or fluoro-A-85380. The full pharmacological profile and the potential for eventual clinical applications of this ligand as a tracer for PET experiments are currently under investigation.
• Synthesis and Nicotinic Acetylcholine Receptor in Vivo Binding Properties of 2-Fluoro-3-[2(<i>S</i>)-2-azetidinylmethoxy]pyridine: A New Positron Emission Tomography Ligand for Nicotinic Receptors
  作者：Frédéric Dollé、Lilian Dolci、Héric Valette、Françoise Hinnen、Françoise Vaufrey、Ilonka Guenther、Chantal Fuseau、Christine Coulon、Michel Bottlaender、Christian Crouzel

  DOI：10.1021/jm9910223

  日期：1999.6.1

  GBq/micromol). In vivo characterization of [18F]F-A-85380 showed promising properties for PET imaging of central nAChRs. This compound does not bind in vivo to alpha7 nicotinic or 5HT3 receptors. Moreover, its cerebral uptake can be modulated by the synaptic concentration of the endogenous ligand acetylcholine. The preliminary PET experiments in baboons with [18F]F-A-85380 show an accumulation of the radiotracer

  一系列新的3-吡啶基醚的先导化合物氮杂环丁烷衍生物A-85380（3-[（（S）-2-azetidinylmethoxymethoxy] pyrididine））是人类alpha4beta2烟碱乙酰胆碱受体（nAChR）的有效和选择性配体亚型。在体外，A-85380的氟衍生物（2-氟-3-[（S）-2-氮杂环丁烷基甲氧基]吡啶或FA-85380）竞争取代[3H]胱氨酸或[3H]表巴替丁，Ki值分别为48和46 pM。FA-85380已由正电子发射极氟18（t1 / 2（半衰期）= 110分钟）标记，且无载体的亲核芳族取代被具有[3- [2]的K [18F] F-K222络合物取代（S）-N-（叔丁氧基羰基）-2-氮杂环丁烷基甲氧基]吡啶-2-基）三甲基铵三氟甲磺酸盐作为高效标记前体，然后用TFA去除Boc保护基。自回旋加速器氟18生产（EOB）结束以来，总合成时间为50-53分钟。相对于最