[18F]2-fluoro-3-[(S)-2-azetidinylmethoxy]pyridine | 205594-65-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [18F]2-fluoro-3-[(S)-2-azetidinylmethoxy]pyridine
• 英文别名: [18F]F-A-85380；[18F]-Fluoro-A 85380；3-(azetidin-2-ylmethoxy)-2-(18F)-pyridine；(18)F-2-A85380；2-Fluoro-3-(2S-azetidinylmethoxy)pyridine, F-18；3-[[(2S)-azetidin-2-yl]methoxy]-2-(18F)fluoranylpyridine
• CAS: 205594-65-6
• 化学式: C₉H₁₁FN₂O
• 分子量: 181.199
• InChiKey: GVOOYVOZPRROMP-GBSHIBCGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  34.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[2-[N-ethyl-N-(2-hydroxyethyl)amino]ethyl]phthalimide 、 2-氟-3-羟基吡啶 、 [18F]2-fluoro-3-[(S)-2-azetidinylmethoxy]pyridine 、 乙酰胆碱 、 三苯基膦 、 偶氮二甲酸二异丙酯 在 氩 、 Al2O3 、 乙酸乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以to give compound 4 (1.77 g, 4.95 mmol) as a yellow solid的产率得到N-[2-[N-ethyl-N-[2-(2-fluoropyridin-3-yloxy)ethyl]amino]ethyl]phthalimide
  参考文献：
  名称：

  Labelled analogues of halobenzamides as multimodal radiopharmaceuticals and their precursors

  摘要：

  本发明涉及公式（I）的化合物： 其中，R1代表氢原子，可选择标记的卤素，放射性核素或Sn[(C1-C4)烷基]3基团； Ar代表芳基或杂芳基； R9代表氢原子，(C1-C4)烷基或与基团R1-Ar一起形成与Ar基团融合的环； A代表公式（β）或（δ）的基团： R3和R4独立地代表氢原子，(C1-C6)烷基，(C1-C6)烯基或公式（γ）的基团： -Y-Z-W-R11（γ） 其中，R11代表可选择标记的卤素，放射性核素，芳基或杂芳基，可选择地被可选择标记的卤素，放射性核素，-NO2基团，-NR5R6基团，-N+R5R6R7X-基团或-OSO2R12基团取代； 以及与药学上可接受的酸形成的加成盐。 本发明还涉及包含它们的制药组合物以及它们在诊断中的应用，特别是在SPECT或PET成像中以及通过靶向放射性核素治疗黑色素瘤的治疗中的应用。

  公开号：

  US09125937B2
• 作为产物：
  描述：

  2-<18F>fluoro-3-<2(S)-(tert-butoxycarbonyl)-2-azetidinylmethoxy>pyridine 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 [18F]2-fluoro-3-[(S)-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 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
• FLUORIDATION OF IODONIUM SALTS
  申请人：Woodcraft John

  公开号：US20110144344A1

  公开（公告）日：2011-06-16

  The present invention provides an improved method for fluoridation of an iodonium salt wherein a solution of the iodonium salt comprising a free radical trap is stored before the reaction is carried out. The method of the invention may be automated, which is particularly convenient when the method of the invention is radiofluoridation. As such the present invention also provides a cassette comprising the iodonium salt solution suitable for carrying out the method of the invention on an automated synthesizer.

  本发明提供了一种改进的碘鎓盐氟化方法，其中在进行反应之前，存储了包含自由基捕捉剂的碘鎓盐的溶液。本发明的方法可以自动化，特别是在进行放射性氟化合物制备时非常方便。因此，本发明还提供了一种盒式装置，其中包含碘鎓盐溶液，适用于在自动化合成器上进行本发明的方法。
• LABELLED ANALOGUES OF HALOBENZAMIDES AS MULTIMODAL RADIOPHARMACEUTICALS AND THEIR PRECURSORS
  申请人：Chezal Jean-Michel

  公开号：US20110044899A1

  公开（公告）日：2011-02-24

  A compound of formula (I): in which R 1 represents a hydrogen atom, an optionally labelled halogen, a radionuclide or a Sn[(C 1 -C 4 )alkyl] 3 group, Ar represents an aryl group or a heteroaryl group, R 9 represents a hydrogen atom, a (C 1 -C 4 ) alkyl group or forms together with the group R 1 —Ar a ring fused with the Ar group, A represents a group of formula (β) or (δ): R 3 and R 4 independently represent a hydrogen atom, a (C 1 -C 6 )alkyl group, a (C 1 -C 6 ) alkenyl group or a group of formula (y): wherein R 11 represents an optionally labelled halogen, a radionuclide, an aryl or heteroaryl group optionally substituted by an optionally labelled halogen, a radionuclide, a —NO 2 group, a —NR 5 R 6 group, a N + R 5 R 6 R 7 X − group, or a —OSO 2 R 12 group, and their addition salts with pharmaceutically acceptable acids.

  化合物的化学式为(I)：其中R1代表氢原子、可选择标记的卤素、放射性核素或Sn[(C1-C4)烷基]3基团，Ar代表芳基或杂芳基，R9代表氢原子、(C1-C4)烷基或与基团R1-Ar共同形成与Ar基团融合的环，A代表化学式(β)或(δ)的基团：R3和R4分别独立地代表氢原子、(C1-C6)烷基、(C1-C6)烯基或化学式(y)的基团：其中R11代表可选择标记的卤素、放射性核素、可选择取代的芳基或杂芳基，取代基可以是可选择标记的卤素、放射性核素、—NO2基团、—NR5R6基团、N+R5R6R7X−基团或—OSO2R12基团，以及它们与药物可接受的酸形成的加合物。
• 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 of a radiotracer for studying nicotinic acetylcholine receptors: 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]A-85380)
  作者：Andrew G. Horti、Andrei O. Koren、Hayden T. Ravert、John L. Musachio、William B. Mathews、Edythe D. London、Robert F. Dannals

  DOI：10.1002/(sici)1099-1344(199804)41:4<309::aid-jlcr78>3.0.co;2-i

  日期：1998.4

  The radiochemical synthesis of 2-[F-18]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[F-18]A-85380, [F-18](1) under bar 1) was accomplished by Kryptofix(R) 222 assisted nucleophilic no-carrier-added [F-18]fluorination of 2-iodo-3-((1-tert-butoxycarbonyl-2 -(S)-azetidinyl)methoxy)pyridine, (2) under bar followed by acidic deprotection. The average radiochemical yield was 10% and the average specific radioactivity was 1050 mCi/mu mol, calculated at end-of-synthesis (EOS).