methyl (1RS-2-exo-3-exo)-8-methyl-3-phenyl-8-azabicyclo<3.2.1>octane-2-carboxylate | 50370-54-2

• 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: methyl (1RS-2-exo-3-exo)-8-methyl-3-phenyl-8-azabicyclo<3.2.1>octane-2-carboxylate
• 英文别名: methyl (1RS-2-exo-3-exo)-8-methyl-3-phenyl-8-azabicyclo[3.2.1]octane-2-carboxylate；methyl (1R,2S,3R,5S)-8-methyl-3-phenyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 50370-54-2；50372-80-0；50583-05-6；57458-42-1；74163-83-0；74163-84-1；127379-25-3；127379-26-4
• 化学式: C₁₆H₂₁NO₂
• 分子量: 259.348
• InChiKey: OMBOXYLBBHNWHL-XQLPTFJDSA-N

物化性质

• 熔点：
  63-65oC
• 溶解度：
  可溶于氯仿（少许）、DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  methyl (1RS-2-exo-3-exo)-8-methyl-3-phenyl-8-azabicyclo<3.2.1>octane-2-carboxylate 在 bis-triphenylphosphine-palladium(II) chloride copper(l) iodide 、 碘 、 silver trifluoromethanesulfonate 、 溶剂黄146 、 二异丙胺 、 锌 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 methyl (1R,2S,3R,5S)-3-(4-((trimethylsilyl)ethynyl)phenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate
  参考文献：
  名称：

  Synthesis and biological evaluation of 2β,3α-(substituted phenyl)nortropanes as potential norepinephrine transporter imaging agents

  摘要：

  A series of 2 beta,3 alpha-(substituted phenyl)nortropanes was synthesized and evaluated in vitro for human monoamine transporters. All compounds studied in this series exhibited nanomolar potency for the norepinephrine transporter (NET). Radiolabeling and nonhuman primate microPET brain imaging studies were performed with the most promising compound, [C-11]1, to determine its utility as a NET imaging agent. Despite high in vitro affinity for the human NET, the high uptake of [C-11]1 in the caudate and putamen excludes its use as an in vivo PET imaging agent for the NET. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.056
• 作为产物：
  描述：

  (1R)-2-(3-methyl-[1,2,4]oxadiazole-5-yl)trop-2-ene 在 盐酸 、 nickel boride 作用下， 以 四氢呋喃 为溶剂， 生成 methyl (1RS-2-exo-3-exo)-8-methyl-3-phenyl-8-azabicyclo<3.2.1>octane-2-carboxylate
  参考文献：
  名称：

  3α-（4'-取代的苯基）tropane-2β-羧酸甲酯：在多巴胺转运蛋白上具有高亲和力和选择性的新型配体。

  摘要：

  DOI：

  10.1021/jm960515u

文献信息

• Dopamine transporter imaging ligand
  申请人：Research Triangle Institute

  公开号：US06358492B1

  公开（公告）日：2002-03-19

  The 3&agr; isomer of RTI-55, RTI-352, is an effective in vivo binding ligand that reflects greater selectivity for the dopamine transporter than is observed with RTI-55. In addition, there is also a more rapid achievement of apparent equilibrium in the striatal-to-cerebellar ratio (compared to RTI-55) as the ratio peaks at about 30 min and is maintained for about 20 min thereafter. Such apparent equilibrium is useful in developing an approach to measuring the number of dopamine transporters present in tissues. Moreover, these results indicate that the utilization of 3&agr; isomers of a variety of 3&bgr;-(substituted phenyl)tropanes will result in greater selectivity for dopamine transporters and a more rapid of achievement of apparent equilibrium.

  RTI-55的3α异构体RTI-352是一种有效的体内结合配体，反映出对多巴胺转运体的更大选择性，这种选择性比RTI-55观察到的要高。此外，与RTI-55相比，在纹状体与小脑比率中也更快地达到明显的平衡状态，比率在约30分钟时达到峰值，此后约维持20分钟。这种明显的平衡状态有助于开发一种测量组织中多巴胺转运体数量的方法。此外，这些结果表明，利用各种3β-(取代苯基)曲梯酮的3α异构体将导致更高的多巴胺转运体选择性和更快的明显平衡状态的实现。
• Synthesis of 3-arylecgonine analogs as inhibitors of cocaine binding and dopamine uptake
  作者：Richard H. Kline、Jeremy Wright、Kristine M. Fox、Mohyee E. Eldefrawi

  DOI：10.1021/jm00169a036

  日期：1990.7

  3-Arylecgonine analogues were synthesized and characterized by 1H and 13C NMR, IR, and MS. The compounds were synthesized as racemates from cycloheptatriene-7-carboxylic acid or enantiomerically from (-)-cocaine. These analogues were tested for their ability to inhibit [3H]cocaine binding to bovine striatal tissue and to inhibit [3H]dopamine uptake into striatal synaptosomes. Methyl (1RS-2-exo-3-exo)-8-methyl-3-phenyl-8-azabicyclo[3.2.1]octane-2-ca rboxylate was the most potent analogue. IC50 values for inhibition of cocaine binding and dopamine uptake were 20 and 100 nM, respectively. The racemates and the 1R isomers were equally potent inhibitors of binding and uptake. Methyl (1RS-2-endo-3-exo)-3-(2,4-dinitrophenyl)-8-methyl-8-azabicyclo[3.2 .1]octane- 2-carboxylate was the least potent. IC50 for inhibition of both binding and uptake was 40 microM.
• Synthesis and binding affinities of 2β-(3-iodoallyloxycarbonyl)-3β-(4-substituted-aryl)tropane analogues as ligands for the dopamine transporter studies
  作者：Kyoo-Hyun Chung、Choong Hwan Lim、Dong Reyoul Lee、Changbae Jin、Dae Yoon Chi

  DOI：10.1016/s0960-894x(01)00625-4

  日期：2001.12

  Tropane analogues from cocaine, which is known to be one of the most reinforcing and addictive compounds, were designed, synthesized, and characterized for inhibition of presynaptic uptake of dopamine (DA) in brain. Eight new derivatives of 3 beta -aryl-2 beta-(3-iodoallyloxycarbonyl)tropanes were synthesized and tested for their potential abilities to displace [H-3]2 beta -carbomethoxy-3 beta-(4-fluorophenyl)tropane (WIN 35,428) binding to the rat striatal membranes. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Monoamine Transporter Binding, Locomotor Activity, and Drug Discrimination Properties of 3-(4-Substituted-phenyl)tropane-2-carboxylic Acid Methyl Ester Isomers
  作者：F. Ivy Carroll、Scott P. Runyon、Philip Abraham、Hernan Navarro、Michael J. Kuhar、Gerald T. Pollard、James L. Howard

  DOI：10.1021/jm0401311

  日期：2004.12.1

  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.
• 3α-(4‘-Substituted phenyl)tropane- 2β-carboxylic Acid Methyl Esters:  Novel Ligands with High Affinity and Selectivity at the Dopamine Transporter
  作者：Christopher R. Holmquist、Kathryn I. Keverline-Frantz、Philip Abraham、John W. Boja、Michael J. Kuhar、F. Ivy Carroll

  DOI：10.1021/jm960515u

  日期：1996.1.1