2-fluoro-3-<2(S)-(tert-butoxycarbonyl)-2-azetidinylmethoxy>pyridine | 205594-61-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 英文名称: 2-fluoro-3-<2(S)-(tert-butoxycarbonyl)-2-azetidinylmethoxy>pyridine
• 英文别名: tert-butyl (2S)-2-[(2-fluoropyridin-3-yl)oxymethyl]azetidine-1-carboxylate
• CAS: 205594-61-2
• 化学式: C₁₄H₁₉FN₂O₃
• 分子量: 282.315
• InChiKey: FFJHTCCUJXLLCZ-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 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：
  51.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-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， 反应 3.0h， 以74%的产率得到Fluoro-A 85380
  参考文献：
  名称：

  Synthesis of a radiotracer for studying nicotinic acetylcholine receptors: 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]A-85380)

  摘要：

  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).

  DOI：

  10.1002/(sici)1099-1344(199804)41:4<309::aid-jlcr78>3.0.co;2-i
• 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-fluoro-3-<2(S)-(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

• 2-, 5-, and 6-Halo-3-(2(<i>S</i>)-azetidinylmethoxy)pyridines:  Synthesis, Affinity for Nicotinic Acetylcholine Receptors, and Molecular Modeling
  作者：Andrei O. Koren、Andrew G. Horti、Alexey G. Mukhin、Daniela Gündisch、Alane S. Kimes、Robert F. Dannals、Edythe D. London

  DOI：10.1021/jm980170a

  日期：1998.9.1

  with high affinity for nicotinic acetylcholine receptors (nAChRs). Here we report the synthesis and in vitro nAChR binding of a series of 10 pyridine-modified analogues of A-85380. The novel compounds feature a halogen substituent at position 2, 5, or 6 of the 3-pyridyl fragment. Those with the substituents at position 5 or 6, as well as the 2-fluoro analogue, possess subnanomolar affinity for nAChRs

  3-（2（S）-氮杂环丁烷基甲氧基）吡啶（A-85380）最近被鉴定为对烟碱乙酰胆碱受体（nAChRs）具有高亲和力的配体。在这里，我们报告的合成和体外nAChR结合的一系列10吡啶修饰的A-85380类似物。新化合物在3-吡啶基片段的2、5或6位具有卤素取代基。那些在5或6位具有取代基的化合物以及2-氟类似物对大鼠脑膜中的nAChR具有亚纳摩尔亲和力。对于这些配体，通过与（+/-）-[3H]表巴替丁竞争测定，Ki值范围为11至210pM。相反，2-氯，2-溴和2-碘类似物表现出低得多的亲和力。AM1量子化学计算表明，位置2的庞大取代基会引起分子几何结构的显着变化。该系列的高亲和力成员和（+）-依巴替丁显示出低能量稳定构象异构体的紧密配合叠加。对nAChRs具有高亲和力的新配体可能会作为药理探针，潜在药物以及开发放射性卤化示踪剂研究nAChRs的候选药物而引起人们的兴趣。
• 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).
• 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
• Dolci; Dolle; Valette, Journal of labelled compounds and radiopharmaceuticals, 1999, vol. 42, # SUPPL. 1, p. S97-S98
  作者：Dolci、Dolle、Valette、Hinnen、Vaufrey、Guenther、Fuseau、Coulon、Bottlaender、Crouzel

  DOI：——

  日期：——