2β-carbomethoxy-3β-(4-fluorophenyl)-8-azabicyclo[3.2.1]octane | 127648-30-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2β-carbomethoxy-3β-(4-fluorophenyl)-8-azabicyclo[3.2.1]octane
• 英文别名: RTI 4229-142；nor-3β-(4-fluorophenyl)tropane-2β-carboxylic acid methyl ester；(1R)-2β-carbomethoxy-3β-(4-fluorophenyl)nortropane；2β-carbomethoxy-3β-(4-fluorophenyl)nortropane；fluoro nortropane；nor-β-CFT；methyl (1R,2S,3S,5S)-3-(4-fluorophenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 127648-30-0
• 化学式: C₁₅H₁₈FNO₂
• 分子量: 263.312
• InChiKey: HQXXRDHSJOKBAP-DGAVXFQQSA-N

物化性质

• 沸点：
  355.2±42.0 °C(Predicted)
• 密度：
  1.170±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2β-carbomethoxy-3β-(4-fluorophenyl)-8-azabicyclo[3.2.1]octane 在 palladium on activated charcoal 氢气 、 potassium iodide 作用下， 以 乙醇 为溶剂， 25.0 ℃ 、68.94 kPa 条件下， 反应 20.0h， 生成 2β-carbomethoxy-3β-(4-fluorophenyl)-8-propylnortropane
  参考文献：
  名称：

  Synthesis and receptor binding of N-substituted tropane derivatives. High-affinity ligands for the cocaine receptor

  摘要：

  The synthesis and pharmacological characterization of a series of N-substituted 3-(4-fluorophenyl)tropane derivatives is reported. The compounds displayed binding characteristics that paralleled those of cocaine, and several had substantially higher affinity at cocaine recognition sites. Conjugate addition of 4-fluorophenyl magnesium bromide to anhydroecgonine methyl ester gave 2-beta-(carbomethoxy)-3-beta-(4-fluorophenyl)tropane (4a, designated CFT, also known as WIN 35,428) after flash chromatography. N demethylation of 4a was effected by Zn/HOAc reduction of the corresponding 2,2,2-trichloroethyl carbamate to give 2-beta-carbomethoxy-3-beta-(4-fluorophenyl)nortropane (5), which was alkylated with allyl bromide to afford the N-allyl analogue, 6. The N-propyl analogue, 7, was prepared by catalytic reduction (Pd/C) of 6. The most potent analogue, 4a, was tritiated at a specific activity of 81.3 Ci/mmol. [H-3]4a bound rapidly and reversibly to caudate putamen membranes; the two-component binding curve typical of cocaine analogues was observed. Equilibrium was achieved within 2 h and was stable for at least 4 h. High- and low-affinity K(d) values observed for [H-3]4a (4.7 and 60 nM, respectively) were more than 4 times lower than those for [H-3]cocaine, and the density of binding sites (B(max) = 50 pmol/g, high, and 290 pmol/g, low) for the two drugs were comparable. Nonspecific binding of [H-3]4a was 5-10% of total binding.

  DOI：

  10.1021/jm00109a029
• 作为产物：
  描述：

  脱水芽子碱甲基酯甲磺酸盐 在 溶剂黄146 、 锌 作用下， 以 乙醚 、 甲苯 为溶剂， 反应 18.0h， 生成 2β-carbomethoxy-3β-(4-fluorophenyl)-8-azabicyclo[3.2.1]octane
  参考文献：
  名称：

  Synthesis and receptor binding of N-substituted tropane derivatives. High-affinity ligands for the cocaine receptor

  摘要：

  The synthesis and pharmacological characterization of a series of N-substituted 3-(4-fluorophenyl)tropane derivatives is reported. The compounds displayed binding characteristics that paralleled those of cocaine, and several had substantially higher affinity at cocaine recognition sites. Conjugate addition of 4-fluorophenyl magnesium bromide to anhydroecgonine methyl ester gave 2-beta-(carbomethoxy)-3-beta-(4-fluorophenyl)tropane (4a, designated CFT, also known as WIN 35,428) after flash chromatography. N demethylation of 4a was effected by Zn/HOAc reduction of the corresponding 2,2,2-trichloroethyl carbamate to give 2-beta-carbomethoxy-3-beta-(4-fluorophenyl)nortropane (5), which was alkylated with allyl bromide to afford the N-allyl analogue, 6. The N-propyl analogue, 7, was prepared by catalytic reduction (Pd/C) of 6. The most potent analogue, 4a, was tritiated at a specific activity of 81.3 Ci/mmol. [H-3]4a bound rapidly and reversibly to caudate putamen membranes; the two-component binding curve typical of cocaine analogues was observed. Equilibrium was achieved within 2 h and was stable for at least 4 h. High- and low-affinity K(d) values observed for [H-3]4a (4.7 and 60 nM, respectively) were more than 4 times lower than those for [H-3]cocaine, and the density of binding sites (B(max) = 50 pmol/g, high, and 290 pmol/g, low) for the two drugs were comparable. Nonspecific binding of [H-3]4a was 5-10% of total binding.

  DOI：

  10.1021/jm00109a029

文献信息

• [EN] BOLAAMPHIPHILIC COMPOUNDS, COMPOSITIONS AND USES THEREOF<br/>[FR] COMPOSITIONS, COMPOSÉS BOLAAMPHIPHILES, ET LEURS UTILISATIONS
  申请人：LAUREN SCIENCES LLC

  公开号：WO2016168580A1

  公开（公告）日：2016-10-20

  Bolaamphiphilic compounds are provided according to formula (I); where HG1, HG2 and L1 are as defined herein. Provided bolaamphiphilic compounds and the pharmaceutical compositions thereof are useful for delivering GDNF or NGF into animal or human brain.

  根据公式（I），提供了双亲嵌段化合物；其中HG1、HG2和L1如本文所定义。提供的双亲嵌段化合物及其制成的药物组合物可用于将GDNF或NGF输送到动物或人类大脑中。
• Preparation of [18F]β-CFT-FP and [11C]β-CFT-FP, selective radioligands for visualisation of the dopamine transporter using positron emission tomography (PET)
  作者：Eeva-Liisa Kämäräinen、Teija Kyllönen、Anu Airaksinen、Camilla Lundkvist、Meixiang Yu、Kjell Någren、Johan Sandell、Oliver Langer、Jouko Vepsäläinen、Jukka Hiltunen、Kim Bergström、Simo Lötjönen、Timo Jaakkola、Christer Halldin

  DOI：10.1002/1099-1344(20001030)43:12<1235::aid-jlcr411>3.0.co;2-9

  日期：2000.10.30

  congener β-CFT (I), N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-fluorophenyl)nortropane (β-CFT-FP, III), was labelled with 18F or 11C. Syntheses of the precursors nor-β-CFT (II) and β-CFT-FP acid (IV) as well as III itself are described. [18F]β-CFT-FP was prepared starting from I using two different labelling reagents: [18F]fluoropropyl bromide (V) and [18F]fluoropropyl tosylate (VI). A reversed-phase HPLC system

  在本研究中，可卡因同系物 β-CFT (I)、N-(3-氟丙基)-2β-carbomethoxy-3β-(4-fluorophenyl)nortropane (β-CFT-FP, III) 的 N-氟丙基类似物是标有 18F 或 11C。描述了前体 Nor-β-CFT (II) 和 β-CFT-FP 酸 (IV) 以及 III 本身的合成。[18F]β-CFT-FP 是从 I 开始使用两种不同的标记试剂制备的：[18F] 氟丙基溴 (V) 和 [18F] 氟丙基甲苯磺酸酯 (VI)。反相 HPLC 系统被证明可以有效地将标记产物与前体 II 分离。V或VI的放射化学掺入产生[18F]β-CFT-FP（18F-III）一般为30-50%，放射化学纯度高于99%。[11C]β-CFT-FP (11C-III) 通过使用 [11C] 三氟甲磺酸甲酯 (VII) 的 IV 酯化合成。事实证明，使用反相柱的
• Simplified synthesis ofN-(3-[18F]fluoropropyl)-2β-carbomethoxy-3β-(4-fluorophenyl)nortropane ([18F]β-CFT-FP) using [18F]fluoropropyl tosylate as the labelling reagent
  作者：Teija Koivula、Outi Perhola、Eeva-Liisa Kämäräinen、Tiina Lipponen、Jouko Vepsäläinen、Olof Solin

  DOI：10.1002/jlcr.943

  日期：2005.5

  A synthesis method has been developed for the labelling of N-(3-[18F]fluoropropyl)-2β-carbomethoxy-3β-(4-fluorophenyl)nortropane ([18F]β-CFT-FP), a potential radioligand for visualization of the dopamine transporters by positron emission tomography. The two-step synthesis includes preparation of [18F]fluoropropyl tosylate and its use without purification in the fluoroalkylation of 2β-carbomethoxy-

  已开发出一种用于标记 N-(3-[18F] 氟丙基)-2β-carbomethoxy-3β-(4-fluorophenyl)nortropane ([18F]β-CFT-FP) 的合成方法，这是一种潜在的放射性配体，用于可视化通过正电子发射断层扫描的多巴胺转运蛋白。两步合成包括制备 [18F] 氟丙基甲苯磺酸酯及其在 2β-carbomethoxy-3β-(4-fluorophenyl)nortropane (nor-β-CFT) 的氟烷基化中的使用，无需纯化。最终产物通过HPLC纯化。两个合成步骤的优化导致 [18F]β-CFT-FP（衰减校正到轰击结束）的放射化学产率超过 30%。包括 HPLC 纯化在内的合成时间约为 90 分钟。最终产品的放射化学纯度高于 99%，合成结束时的比放射性通常为 20 GBq/µmol。与 [18F] 氟丙基溴的烷基化相比，此处描述的程序可在更短的时间内提高
• Synthesis and monoamine uptake inhibition of conformationally constrained 2β-carbomethoxy-3β-phenyl tropanes
  作者：Patrick Johannes Riss、René Hummerich、Patrick Schloss

  DOI：10.1039/b902863c

  日期：——

  A series of 2β-carbomethoxy-3β-phenyl tropanes with conformationally constrained nitrogen substituents were synthesized as potential selective dopamine transporter ligands. These novel compounds were examined for their monoamine uptake inhibition potency at the human dopamine transporter (hDAT), the human serotonin transporter (hSERT) and the human noradrenalin transporter (hNET), stably expressed

  合成了一系列具有构象约束的氮取代基的2β-羰甲氧基-3β-苯基托烷，作为潜在的选择性 多巴胺转运体配体。对这些新型化合物进行了检查一元胺 对人体的吸收抑制能力 多巴胺 运输者（hDAT）， 人类 血清素 运输者（hSERT）和人类 去甲肾上腺素 运输者（网络），在人类胚胎肾细胞（HEK）中稳定表达。进行了SAR研究，以确定在C链上延伸的，4-氟化，构象受限的C 4链的贡献。托烷 氮对人 一元胺 转运蛋白的亲和力和选择性。
• Fluoralkenyl nortropanes
  申请人：Emory University

  公开号：US06344179B1

  公开（公告）日：2002-02-05

  Provided are compounds of the following formula: wherein R is C2-C6 mono- or multi-unsaturated hydrocarbon having one or more ethylene, acetylene or allene groups, A is 18 or 19, and X is H or halogen. The compounds of the invention bind to dopamine transporter with high affinity and selectivity and are thus useful as diagnostic and therapeutic agents for diseases associated with dopamine transporter dysfunction. The radiolabeled compounds are useful as imaging agents for visualizing the location and density of dopamine transporter by PET imaging.

  提供的化合物具有以下公式：其中R是具有一个或多个乙烯、乙炔或戊二烯基团的C2-C6单烯烃或多烯烃碳氢化合物，A为18或19，X为H或卤素。该发明的化合物具有高亲和力和选择性地结合多巴胺转运蛋白，因此可用作与多巴胺转运蛋白功能障碍相关的疾病的诊断和治疗药物。放射标记的化合物可用作PET成像来可视化多巴胺转运蛋白的位置和密度。