3β-(4'-bromophenyl)tropane | 135367-08-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: 3β-(4'-bromophenyl)tropane
• 英文别名: β-CBT；RTI 51；2β-carbomethoxy-3β-(4-bromophenyl)tropane；2beta-Carbomethoxy-3beta(4'-bromophenyl)tropane；methyl (1R,2S,3S,5S)-3-(4-bromophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 135367-08-7
• 化学式: C₁₆H₂₀BrNO₂
• 分子量: 338.244
• InChiKey: HNVGNUVAMRLMSG-YJNKXOJESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3β-(4'-bromophenyl)tropane 在 sodium 作用下， 以 甲醇 为溶剂， 反应 27.0h， 以66%的产率得到(1R)-3β-(4-bromophenyl)tropane-2α-carboxylic acid methyl ester
  参考文献：
  名称：

  Monoamine Transporter Binding, Locomotor Activity, and Drug Discrimination Properties of 3-(4-Substituted-phenyl)tropane-2-carboxylic Acid Methyl Ester Isomers

  摘要：

  The monoamine transporter binding properties, gross behavior, and locomotor activity effects in mice and drug discrimination results in cocaine-trained rats of the 2beta3beta-, 2beta,3alpha-, 2alpha-,3beta-, and 2alpha-,3alpha-isomers of several 3-(4-substituted-phenyl)tropane carboxylic acid methyl esters were compared (2a-f, 3a-f, 4a-f, and 5b,c). The 2beta,3beta-isomer showed the highest affinity for the dopamine transporter (DAT), and the 2beta,3alpha-isomer showed the next highest affinity. The order of potency for the 2beta,3beta-isomer is 4'-chloro (2c) = 4'-iodo (2e) > 4'-bromo (2d) = 4'-methyl (2f) > 4'-fluoro (2b) > 4'-hydrogen (2a). In the case of the 2beta,3alpha-isomer, the order of affinity was 4'-bromo (3d) > 4'-iodo (3e) = 4'- chloro (3c) > 4'-methyl (3f) > 4'-fluoro (3b) > 4'-hydrogen (3a). The 4'-hydrogen, 4'-fluoro, and 4'-methyl 2alpha,3beta-isomers, 4a, 4b, and 4f, had the lowest affinity for the DAY While most of the compounds showed their highest affinity at the DAT, none were selective relative to the other two monoamine transporters. In general, the 2alpha,3alpha- and 2alpha,3beta-isomers were more toxic (death and convulsions) than the 2beta,3beta- and 2beta,3alpha-isomers. With the exception of the 2(x,3a-isomers, all compounds produced the locomotor activity stimulation typical of dopaminergic drugs. The ED50 ranges for the 2beta,3beta- (2a-f), 2beta,3alpha- (3a-f), and 2alpha,3alpha-isomers (4a-f) in the locomotor assay were 0.1-1.2, 6.6-21.8, and 2.4-11.7 mg/kg, respectively. With the exception of the 2a,3a-isomer, all compounds generalized to cocaine. The 2beta,3beta-isomers were at least 10-fold more potent than cocaine and the other three sets of isomers in this test.

  DOI：

  10.1021/jm0401311
• 作为产物：
  描述：

  (4-(trimethylsilyl)phenyl)magnesium bromide 在 N-氯代丁二酰亚胺 、 溶剂黄146 、 sodium bromide 作用下， 以 乙醚 为溶剂， 生成 3β-(4'-bromophenyl)tropane
  参考文献：
  名称：

  一系列新型的托烷N-或O-氟代烷基衍生物的合成和生物学评估：多巴胺转运蛋白的潜在正电子发射断层扫描（PET）成像剂。

  摘要：

  合成了一系列新颖的含氟烷基的托烷衍生物，并通过竞争性结合试验确定了它们与多巴胺转运蛋白（DAT），5-羟色胺转运蛋白（SERT）和去甲肾上腺素转运蛋白（NET）的结合亲和力。在这些衍生物中，β-CIT的氟丙基酯（19），β-CIT的氟乙基酯（20），β-CBT的N-氟丙基衍生物（12）和β-CMT的氟丙基酯（18）与FP-CIT相比，DAT对SERT和NET具有更高的亲和力和更高的选择性，这表明它们对于DAT的（18）F标记PET显像剂的开发具有吸引力。

  DOI：

  10.1016/s0960-894x(01)00626-6

文献信息

• Synthesis, Radiosynthesis, and Biological Evaluation of Carbon-11 and Fluorine-18 (<i>N</i>-Fluoroalkyl) Labeled 2β-Carbomethoxy-3β-(4'-(3-furyl)phenyl)tropanes and -nortropanes:  Candidate Radioligands for in Vivo Imaging of the Serotonin Transporter with Positron Emission Tomography
  作者：Jeffrey S. Stehouwer、Christophe Plisson、Nachwa Jarkas、Fanxing Zeng、Ronald J. Voll、Larry Williams、Laurent Martarello、John R. Votaw、Gilles Tamagnan、Mark M. Goodman

  DOI：10.1021/jm0504095

  日期：2005.11.1

  N-fluorobutyl (5) derivatives. The binding affinity for each compound to the human serotonin, dopamine, and norepinephrine transporters was determined using transfected HEK-293 cells. Radiolabeling and microPET brain imaging studies were performed with [(11)C]1, [(11)C]2, and [(18)F]3 to determine their utility as in vivo imaging agents.

  与N-甲基（2），N-氟乙基（3），N-氟丙基（4）和N-氟丁基（5）衍生物。使用转染的HEK-293细胞确定每种化合物对人血清素，多巴胺和去甲肾上腺素转运蛋白的结合亲和力。用[（11）C] 1，[（11）C] 2和[（18）F] 3进行了放射性标记和microPET脑成像研究，以确定它们作为体内成像剂的效用。
• [EN] METHOD FOR THE PREPARATION OF N-MONOFLUOROALKYL TROPANES AND THEIR USE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE N-MONOFLUOROALKYL-TROPANES ET LEUR UTILISATION
  申请人：ROTOP RADIOPHARMACY GMBH

  公开号：WO2021148598A1

  公开（公告）日：2021-07-29

  The present invention relates to a method for the preparation of an N-monofluoroalkyl tropane, a method for the preparation of a trialkyltin tropane, a method for the preparation of an iodinated and/or radioiodinated tropane and the use of the N-monofluoroalkyl tropane as a precursor in the method for the preparation of the trialkyltin tropane and/or the iodinated and/or radioiodinated tropane.

  本发明涉及一种制备N-单氟烷基曲巴克碱的方法，一种制备三烷基锡曲巴克碱的方法，一种制备碘化和/或放射碘化曲巴克碱的方法，以及将N-单氟烷基曲巴克碱用作三烷基锡曲巴克碱和/或碘化和/或放射碘化曲巴克碱制备方法中的前体的用途。
• 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。
• Synthesis and amine transporter affinities of novel phenyltropane derivatives as potential positron emission tomography (PET) imaging agents
  作者：Xuemei Peng、Ao Zhang、Nora S. Kula、Ross J. Baldessarini、John L. Neumeyer

  DOI：10.1016/j.bmcl.2004.08.049

  日期：2004.11

  A series of novel fluoroalkyl-containing tropane derivatives (6-8, 10-14, 17, and 18) were synthesized from cocaine. Novel compounds were evaluated for affinity and selectivity in competitive radioligand binding assays selective for cerebral serotonin (5-HT), dopamine (DA), and norepinephrine (NE) transporters (SERT, DAT, and NET). The nortropane-fluoroalkyl esters (7, 10, 11) were most potent for

  从可卡因合成了一系列新颖的含氟烷基的托烷衍生物（6-8、10-14、17和18）。在竞争性放射性配体结合测定法中对脑5-羟色胺（5-HT），多巴胺（DA）和去甲肾上腺素（NE）转运蛋白（SERT，DAT和NET）有选择性，对新型化合物的亲和力和选择性进行了评估。降冰片烷-氟代烷基酯（7、10、11）对SERT最有效（K（i）：分别为0.18、0.24和0.30 nM）。甲苯磺酸酯17和18，合成为[（18）F]标记的正电子发射断层扫描（PET）成像剂的前体，也显示出对DAT的高亲和力。
• Synthesis, Radiosynthesis, and Biological Evaluation of Carbon-11 and Iodine-123 Labeled 2β-Carbomethoxy-3β-[4‘-((<i>Z</i>)-2-haloethenyl)phenyl]tropanes:  Candidate Radioligands for in Vivo Imaging of the Serotonin Transporter
  作者：Christophe Plisson、Jonathan McConathy、Laurent Martarello、Eugene. J. Malveaux、Vernon M. Camp、Larry Williams、John R. Votaw、Mark M. Goodman

  DOI：10.1021/jm030384e

  日期：2004.2.1

  2beta-Carbomethoxy-3beta-[4'-((Z)-2-iodoethenyl)phenyl]tropane (ZIET) and 2beta-carbomethoxy-3beta-[4'-((Z)-2-bromoethenyl)phenyl]tropane (ZBrET) were synthesized as well as their nortropane congeners ZIENT and ZBrENT. Binding affinities of these compounds were determined in cells transfected to express human SERT, DAT, and NET using [3H]citalopram, [125I]RTI-55, and [3H]nisoxetine, respectively. Both

  2beta-Carbomethoxy-3beta- [4'-（（（Z）-2-iodoethenyl）phenyl] tropane（ZIET）和2beta-carbomethoxy-3beta- [4'-（（（Z）-2-bromoethenyl] phenyl] tropane（ZBrET ）以及它们的正烷烃同系物ZIENT和ZBrENT。使用[3H]西酞普兰，[125I] RTI-55和[3H]尼西西汀分别测定转染表达人SERT，DAT和NET的细胞中这些化合物的结合亲和力。ZIET和ZBrET都显示出对SERT的高度亲和力（分别为Ki = 0.11和0.08 nM）。ZIET和ZBrET对DAT的亲和力分别比SERT低200倍和38倍。[11C] ZIET和[11C] ZBrET是通过用[11C]甲基碘将其相应的降冰片烷进行烷基化制备的，其放射化学收率约为30％（衰减校正至轰击结束，EOB）。高比活度[123I]