(1R,2S,3S,5S)-8-甲基-3-苯基-8-氮杂双环[3.2.1]辛烷-2-羧酸甲酯 | 50372-80-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 中文名称: (1R,2S,3S,5S)-8-甲基-3-苯基-8-氮杂双环[3.2.1]辛烷-2-羧酸甲酯
• 英文名称: WIN 35,065-2
• 英文别名: methyl (1R,5S)-3β-phenyltropane-2β-carboxylate；Win 35065-2；(1R)-3β-phenyl-8-methyl-8-azabicyclo<3.2.1>octane-2β-carboxylic acid methyl ester；methyl <1R-(exo,exo)>-8-methyl-3-phenyl-8-azabicyclo<3.2.1>octane-2-carboxylate；methyl 3β-phenyltropane-2β-carboxylate；2-β-carbomethoxy-3-β-phenyltropane；Troparil；methyl (1R,2S,3S,5S)-8-methyl-3-phenyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 50372-80-0
• 化学式: C₁₆H₂₁NO₂
• 分子量: 259.348
• InChiKey: OMBOXYLBBHNWHL-YJNKXOJESA-N

物化性质

• 熔点：
  56-59°C
• 沸点：
  350.2±42.0 °C(Predicted)
• 密度：
  1.099±0.06 g/cm3(Predicted)
• 溶解度：
  在水中可溶

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：

  (1R,2S,3S,5S)-8-甲基-3-苯基-8-氮杂双环[3.2.1]辛烷-2-羧酸甲酯 在 lithium aluminium tetrahydride 、 草酰氯 、 三乙胺 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 乙醚 、 乙腈 为溶剂， 反应 25.0h， 生成 2β-(3'-hydroxyprop-1-enyl)-3β-phenyltropane
  参考文献：
  名称：

  Synthesis, Dopamine Transporter Affinity, Dopamine Uptake Inhibition, and Locomotor Stimulant Activity of 2-Substituted 3β-Phenyltropane Derivatives

  摘要：

  A series of 2 beta-substituted 3 beta-phenyltropanes were synthesized as analogs of cocaine and tested in vitro for their ability to displace bound [H-3]WIN 35,428 (2b) and inhibit; dopamine uptake in rat caudate-putamen tissue. The analogs bound with high affinity (K-i = 11-22 nM) to the dopamine transporter. Increased lipophilicity at the beta-C(2)-position was found to lead to increased binding affinity and increased dopamine uptake potency. However, a direct correlation between clogP values and binding affinity and potency of uptake inhibition was not observed. The unsaturated ester 7 was found to possess weak dopamine uptake inhibition relative to the high binding affinity (IC50/K-i = 10.2). In vivo measurement of stimulated locomotor activity and drug discrimination against cocaine (10 mg/kg, ip) with selected analogs (4, 6, and 7) demonstrated that the behavioral effects of these drugs were approximately equipotent with those of cocaine, The structure-activity relationships of this series of cocaine analogs supports a pharmacophore model in which lipophilic interactions between the B-C(2)position of 3 beta-phenyltropanes and the cocaine binding site on the dopamine transporter lead to enhanced potency while electrostatic interactions have a nonspecific effect.

  DOI：

  10.1021/jm960739c
• 作为产物：
  描述：

  古卡因 在 盐酸 、 三氯氧磷 作用下， 以 乙醚 为溶剂， 生成 (1R,2S,3S,5S)-8-甲基-3-苯基-8-氮杂双环[3.2.1]辛烷-2-羧酸甲酯
  参考文献：
  名称：

  Synthesis and monoamine transporter affinity of 2β-carbomethoxy-3β-(2″-, 3″- or 4″-substituted) biphenyltropanes

  摘要：

  A series of 11 novel 3 beta-substituted biphenyltropanes was synthesized and evaluated by selective radioligand binding assays for affinity to monoamine transporters. Both 5-HTT potency and selectivity for 5-HTT over DAT was greatest with electron withdrawing group at the 3"-position. (C) 2000 Elsevier Science Ltd. All fights reserved.

  DOI：

  10.1016/s0960-894x(00)00317-6

文献信息

• Tropane derivatives and method for their synthesis
  申请人：Georgetown University

  公开号：US06350758B1

  公开（公告）日：2002-02-26

  A compound of formula (I) wherein R1-R6 have any of the values defined in the specification are described, as well as pharmaceutical compositions comprising a compound of formula (I), and methods for preparing and using compounds of formula (I) are described.

  公式（I）的化合物，其中R1-R6具有规范中定义的任何值，以及包括公式（I）的化合物的药物组合物，以及描述了制备和使用公式（I）化合物的方法。
• 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 and 3.beta.-(4'-Substituted phenyl)tropane-2.beta.-carboxylic Acid Ester and Amide Analogs. New High-Affinity and Selective Compounds for the Dopamine Transporter
  作者：F. Ivy Carroll、Pravin Kotian、Ali Dehghani、Jeffrey L. Gray、Michael A. Kuzemko、Karol A. Parham、Philip Abraham、Anita H. Lewin、John W. Boja、Michael J. Kuhar

  DOI：10.1021/jm00002a020

  日期：1995.1

  2 beta-carboxylic acid are highly potent and highly selective for the DA transporter. The isopropyl esters of 3 beta-(4'-chlorophenyl)- and 3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid also possess high DA affinity and show significant DA transporter selectivity. Similarly, the phenyl and isopropyl ester analogues of cocaine are much more selective for the DA transporter than cocaine. Tertiary

  制备了几种可卡因的2-β-羧酸酯和酰胺类似物以及3-β-（4'-取代的苯基）tropane-2β-羧酸的酰胺类似物。确定了这些化合物以及一些先前制备的类似物在多巴胺（DA），去甲肾上腺素（NE）和血清素（5-HT）转运蛋白上的结合亲和力。3β-（4'-甲基苯基）-和3β-（4'-氯苯基）托烷-2β-羧酸的苯基酯对DA转运蛋白具有很高的效力和选择性。3β-（4'-氯苯基）-和3β-（4'-碘苯基）托烷-2β-羧酸的异丙酯也具有较高的DA亲和力，并显示出显着的DA转运蛋白选择性。同样，可卡因的苯基和异丙基酯类似物对DA转运蛋白的选择性比可卡因高得多。可卡因和3个β-（4'-取代的苯基）tropane-2β-羧酸的叔酰胺类似物比伯胺和仲酰胺类似物在DA转运蛋白上更有效地抑制放射性配体结合。特别是，3β-（4'-氯苯基）tropane-2β-N-吗啉代羧酰胺以及3β-（4'-氯苯基）-和3β-（4'-碘苯基）tropane-2
• [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。
• 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。