(1R,5S)-2β,3β-diphenyltropane | 208989-39-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: (1R,5S)-2β,3β-diphenyltropane
• 英文别名: 2β,3β-diphenyltropane；(1R,5S)-2β-phenyl-3β-phenyltropane；(1R,2R,3S,5S)-8-methyl-2,3-diphenyl-8-azabicyclo[3.2.1]octane
• CAS: 208989-39-3
• 化学式: C₂₀H₂₃N
• 分子量: 277.409
• InChiKey: URXGPOFPBIBVGT-NMLBUPMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  (1R,5S)-2-Isocyanato-8-methyl-3-phenyl-8-aza-bicyclo[3.2.1]oct-2-ene 在 palladium on activated charcoal 盐酸 、 lithium aluminium tetrahydride 、 氢溴酸 、 碳酸氢钠 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 反应 135.25h， 生成 (1R,5S)-2β,3β-diphenyltropane
  参考文献：
  名称：

  Synthesis and Monoamine Transporter Binding Properties of 2,3-Diaryltropanes

  摘要：

  Synthetic procedures were developed for the synthesis of 2 beta,3 beta- and 2 alpha,3 alpha-diaryltropanes. These compounds are analogues of the 3-aryltropane-2 beta-carboxylic acid methyl ester class of monoamine uptake inhibitors, where the 2 beta-carbomethoxy group has been replaced by an aryl group. The compounds were evaluated for inhibition of radioligand binding at the dopamine, norepinephrine, and serotonin transporters (DAT, NET, and 5-HTT, respectively). The results showed that the replacement of the 2 beta-carbomethoxy group in the 3-aryltropane class with a 2 beta-aryl group led to compounds possessing very similar monoamine transporter binding properties. However, the 2 beta,3 beta-diaryltropanes tended to be more potent at the DAT and more selective for the DAT relative to the NET and 5-HTT. One of the most interesting compounds was 3 beta-(4-methylphenyl)-2 beta-(4-methylphenyl)tropane (3d), which showed an IC50 of 1.23 nM at the DAT with 289- and 185-fold selectivity for the DAT relative to the NET and 5-HTT. The 2 alpha,3 alpha-diaryltropanes were much less potent at all three transporters than 2 beta,3 beta-diaryltropanes.

  DOI：

  10.1021/jm0582423

文献信息

• Synthesis and Biological Properties of New 2β-Alkyl- and 2β-Aryl-3-(substituted phenyl)tropane Derivatives:  Stereochemical Effect of C-3 on Affinity and Selectivity for Neuronal Dopamine and Serotonin Transporters
  作者：Alan P. Kozikowski、Gian Luca Araldi、K. R. C. Prakash、Mei Zhang、Kenneth M. Johnson

  DOI：10.1021/jm9802564

  日期：1998.12.1

  present work is a 2, 3-diaryltropane 22 in a boat conformation that is highly selective (69-fold) for the DAT over the 5HTT. The ability to prepare this compound as well as related structures by our oxidopyridinium betaine-based dipolar cycloaddition strategy further underscores the versatility of this particular chemical approach to the preparation of diverse tropane analogues. The use of the optically

  在努力确定可能充当可卡因拮抗剂或可卡因部分激动剂的分子的过程中，我们参与了通过结构上的战略性修饰来进一步阐明可卡因与多巴胺转运蛋白（DAT）结合的性质的努力。在取代基位于托环环的2位的情况下，研究表明转运蛋白能够容纳多种结构的基团，包括酯，酮，烷基，烯基，杂环和芳基取代基，而不会损失DAT绑定亲和力。在本研究中，我们报告了有关DAT容纳WIN型结构的能力的结果，该结构在2位具有烷基或芳基，并且采用了环烷的椅子或船形。而且，我们讨论了这些化合物的立体化学对DAT相对于血清素转运蛋白（5HTT）的选择性的影响。此外，我们指出了在进行转运蛋白选择性的比较时，使用Ki值而不是IC50值的重要性。在本研究中鉴定出的最有趣的化合物之一是船形的2，3-二芳基托烷22，它对DAT的选择性比5HTT高（69倍）。通过我们基于氧化吡啶鎓甜菜碱的偶极环加成策略制备该化合物及相关结构的能力进一步强调了这种特殊化学
• Cocaine receptor binding ligands
  申请人：RESEARCH TRIANGLE INSTITUTE

  公开号：US20030023090A1

  公开（公告）日：2003-01-30

  The invention relates to novel compounds which show high affinity for cocaine receptors in the brain, particularly dopamine and serotonin transporter sites. The compounds may be used as imaging or pharmaceutical agents, in the diagnosis and treatment of drug addiction, depression, anorexia and neurodegenerative diseases.

  本发明涉及新型化合物，其在大脑中表现出对可卡因受体的高亲和力，特别是对多巴胺和血清素转运体位点。这些化合物可用作成像或药物剂量，在药物成瘾、抑郁症、厌食症和神经退行性疾病的诊断和治疗中使用。
• [EN] COCAINE RECEPTOR BINDING LIGANDS<br/>[FR] LIGANDS SE FIXANT SUR LES RECEPTEURS DE COCAINE
  申请人：RESEARCH TRIANGLE INSTITUTE

  公开号：WO1999061023A1

  公开（公告）日：1999-12-02

  (EN) The invention relates to novel compounds which show high affinity for cocaine receptors in the brain, particularly dopamine and serotonin transporter sites. The compounds may be used as imaging or pharmaceutical agents, in the diagnosis and treatment of drug addiction, depression, anorexia and neurodegenerative diseases.(FR) L'invention concerne de nouveaux composés présentant une forte affinité pour les récepteurs de la cocaïne dans le cerveau, en particulier pour les sites transporteurs de dopamine et de sérotonine. Ces composés peuvent être utilisés comme agents de visualisation ou comme agents pharmaceutiques pour le diagnostic et le traitement de la toxicomanie, de la dépression, de l'anorexie et des maladies neurodégénératives.

  该发明涉及一种新型化合物，其在大脑中表现出高亲和力，特别是在多巴胺和5-羟色胺转运体位点。这些化合物可用作成像或药物剂，用于诊断和治疗药物成瘾、抑郁症、厌食症和神经退行性疾病。
• Synthesis and transporter binding properties of (R)-2β,3β- and (R)-2α,3α-diaryltropanes
  作者：Songchun Jiang、An-Chih Chang、Philip Abraham、Michael J. Kuhar、F.Ivy Carroll

  DOI：10.1016/s0960-894x(98)00673-8

  日期：1998.12

  (R)-2-Aryl-2-tropinone (9) was synthesized from (R)-2-carbomethoxy-3-tropinone (5) and was used as the key intermediate for the synthesis of (R)-2 beta,3 beta- and (R)-2 alpha,3 alpha-diaryltropanes. Inhibition of radioligand binding studies at the dopamine, serotonin, and norepinephrine transporters showed that the (R)-3 beta-(4-methylphenyl)-2 beta-phenyltropane (3b, RTI-422) possessed an IC50 value of 1.96 nM at the dopamine transporter and was highly selective for this transporter relative to the serotonin and norepinephrine transporters. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Synthesis and Transporter Binding Properties of 2,3-Diphenyltropane Stereoisomers. Comparison to 3β-Phenyltropane-2β-carboxylic Acid Esters
  作者：An-Chih Chang、Jason P. Burgess、S. Wayne Mascarella、Philip Abraham、Michael J. Kuhar、F. Ivy Carroll

  DOI：10.1021/jm960703k

  日期：1997.4.1

  2 beta,3 beta-Diphenyl-(5), 2 alpha,3 alpha-diphenyl-(6), and 2 alpha,3 beta-diphenyltropane (3) as well as 2,3-diphenyltrop-2-ene (4) were prepared in racemic form and assayed for inhibition of radioligand binding at the dopamine (DA), serotonin (5-HT), and norepinephrine (NE) transporters. Among all three transporters, compounds 4-6 bound the DA transporter with the highest affinity. The 2 beta,3 beta-diphenyltropane (5) bound the DA transporter with an IC50 value (28 nM) almost identical to that of 3 beta-phenyltropane-2 beta-carboxylic acid methyl ester (WIN 35,065-2) and has much greater selectivity relative to binding to the serotonin transporter. A comparison of the radioligand data from this study to radioligand data obtained on other WIN 35,065-2 analogs suggests that hydrophobicity of the C-2 substituent of some analogs of the WIN 35,065-2 class may be an important contributing factor to binding at the DA transporter.