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