3α-(4-methylphenyl)tropane-2β-carboxylic acid methyl ester | 184376-55-4

• 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: 3α-(4-methylphenyl)tropane-2β-carboxylic acid methyl ester
• 英文别名: methyl (1R,2S,3R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 184376-55-4
• 化学式: C₁₇H₂₃NO₂
• 分子量: 273.375
• InChiKey: MMKZDDDDODERSJ-JONQDZQNSA-N

物化性质

• 沸点：
  368.7±42.0 °C(Predicted)
• 密度：
  1.084±0.06 g/cm3(Predicted)
• 溶解度：
  溶于二氯甲烷；甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  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：
  0.59
• 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：

  3α-(4-methylphenyl)tropane-2β-carboxylic acid methyl ester 生成 3α-(4-methylphenyl)tropane-2β-carboxylic acid methyl ester tosylate
  参考文献：
  名称：

  Dopamine transporter imaging ligand

  摘要：

  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。

  公开号：

  US06358492B1
• 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 3α-(4-methylphenyl)tropane-2β-carboxylic acid methyl ester
  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

• Synthesis and Monoamine Transporter Binding Properties of 3α-(Substituted phenyl)nortropane-2β-carboxylic Acid Methyl Esters. Norepinephrine Transporter Selective Compounds
  作者：F. Ivy Carroll、Sameer Tyagi、Bruce E. Blough、Michael J. Kuhar、Hernn A. Navarro

  DOI：10.1021/jm058164j

  日期：2005.6.1

  3alpha-(substituted phenyl)nortropane-2beta-carboxylic acid methyl esters (8a-h) showed high affinity for the norepinephrine transporter (NET). The most potent and selective compound was 3alpha-(3-fluoro-4-methylphenyl)nortropane-2beta-carboxylic acid methyl ester (8d), with a Ki of 0.43 nM at the NET and 21- and 55-fold selectivity relative to binding at the dopamine and serotonin transporters. The development

  3α-（取代的苯基）降冰片烷2β-羧酸甲酯（8a-h）对去甲肾上腺素转运蛋白（NET）有很高的亲和力。最有效和选择性最大的化合物是3alpha-（3-氟-4-甲基苯基）降冰片烷2β-羧酸甲酯（8d），在NET处的Ki值为0.43 nM，相对于结合的选择性为21倍和55倍多巴胺和5-羟色胺转运蛋白。8d的发展使具有相同结构类别的所有三种转运蛋白具有选择性的可用化合物。
• 3α-(4-Substituted phenyl)nortropane-2β-carboxylic acid methyl esters show selective binding at the norepinephrine transporter
  作者：Bruce E Blough、Christopher R Holmquist、Philip Abraham、Michael J Kuhar、F.Ivy Carroll

  DOI：10.1016/s0960-894x(00)00480-7

  日期：2000.11

  of 3alpha-(4-substituted)nortropane-2beta-carboxylic acid methyl esters was synthesized and evaluated for the ability to inhibit radioligand binding at the dopamine, serotonin, and norepinephrine transporters. 3alpha-(4-Methylphenyl)nortropane-2beta-carboxylic acid methyl ester (4c) was found to be selective and highly potent for the norepinephrine transporter (NET) relative to the dopamine and serotonin

  合成了一系列的3α-（4-取代）降冰片烷2β-羧酸甲酯，并评估了在多巴胺，5-羟色胺和去甲肾上腺素转运蛋白上抑制放射性配体结合的能力。发现3α-（4-甲基苯基）降冰片烷2β-羧酸甲酯（4c）对去甲肾上腺素转运蛋白（NET）相对于多巴胺和5-羟色胺转运蛋白具有选择性和高效力。
• 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.
• 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。
• 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