3β-(4'-vinylphenyl)tropane-2β-carboxylic acid methyl ester | 181796-42-9

• 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'-vinylphenyl)tropane-2β-carboxylic acid methyl ester
• 英文别名: 2beta-Carbomethoxy-3beta-(4'-ethenylphenyl)tropane；methyl (1R,2S,3S,5S)-3-(4-ethenylphenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 181796-42-9
• 化学式: C₁₈H₂₃NO₂
• 分子量: 285.386
• InChiKey: WZTGKIRRMQSWDD-HZMVEIRTSA-N

物化性质

• 沸点：
  388.9±42.0 °C(Predicted)
• 密度：
  1.090±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 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'-vinylphenyl)tropane-2β-carboxylic acid methyl ester 在 palladium on activated charcoal 甲醇 、 1-氯乙基氯甲酸酯 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 4.0h， 生成 3β-(4'-ethylphenyl)nortropane-2β-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis and Transporter Binding Properties of 3β-(4‘-Alkyl-, 4‘-alkenyl-, and 4‘-alkynylphenyl)nortropane-2β-carboxylic Acid Methyl Esters:  Serotonin Transporter Selective Analogs

  摘要：

  New methods for the synthesis of 3 beta-(4'-alkyl-, 4'-alkenyl-, and 4'-alkynylphenyl)nortropane-2 beta-carboxylic acid methyl esters 2-4, respectively, were developed. These methods involved coupling of the appropriate organometallic reagents to 3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (6a, RTI-55) or to an N-protected derivative of 6a followed by N-demethylation or removal of the protecting group. Some analogs were prepared by catalytic reduction of the alkene and alkyne analogs 3 and 4 or by isomerization of the alkenes 3. The analogs 2-4 were evaluated for inhibition of radioligand binding to the serotonin (5-HT), dopamine (DA), and norepinephrine (NE) transporters. 3 beta-(4'-Isopropenyl- and 4'-cis-propenylphenyl)nortropane-2 beta-carboxylic acid methyl esters (3b,d), which possessed IC50 values of 0.6 and 1.15 nM, respectively, were the most potent analogs at the 5-HT transporter, and with NE/5-HT IC50 ratios of 240 and 128 nM, respectively, they were selective for the 5-HT relative to the NE transporter. Since interaction with the serotonin transporter may modulate the pharmacological effects resulting from binding to the dopamine transporter, 3 beta-(4'-isopropenylphenyl)tropane-2 beta-carboxylic acid methyl ester (11b) which has good affinity for both the 5-HT and DA transporters but low affinity at the NE transporter may be useful for studying this interaction.

  DOI：

  10.1021/jm960409s
• 作为产物：
  描述：

  (4-(trimethylsilyl)phenyl)magnesium bromide 在 四(三苯基膦)钯 N-氯代丁二酰亚胺 、 potassium bromide 作用下， 生成 3β-(4'-vinylphenyl)tropane-2β-carboxylic acid methyl ester
  参考文献：
  名称：

  Chen; Kilts; Camp, Journal of labelled compounds and radiopharmaceuticals, 1999, vol. 42, # SUPPL. 1, p. S324-S326

  摘要：

  DOI：

文献信息

• 4-haloethenylphenyl tropane:serotonin transporter imaging agents
  申请人：Goodman Mark M.

  公开号：US06843979B2

  公开（公告）日：2005-01-18

  A series of compounds in the 4-fluoroalkyl-3-halophenyl nortropanes and 4-haloethenylphenyl tropane families are described as diagnostic and therapeutic agents for diseases associated with serotonin transporter dysfunction. These compounds bind to serotonin transporter protein with high affinity and selectivity. The invention provides methods of synthesis which incorporate radioisotopic halogens at a last step which permit high radiochemical yield and maximum usable product life. The radiolabeled compounds of the invention are useful as imaging agents for visualizing the location and density of serotonin transporter by PET and SPECT imaging.

  一系列4-氟烷基-3-卤代苯基诺特罗帕尼和4-卤乙烯基苯基曲罗平类化合物被描述为与血清素转运蛋白结合的诊断和治疗剂，用于与血清素转运蛋白功能障碍相关的疾病。这些化合物具有高亲和力和选择性，可结合到血清素转运蛋白蛋白质上。本发明提供了合成方法，其中在最后一步中引入放射性同位素卤素，从而允许高放射化学产率和最大可用产品寿命。本发明的放射性标记化合物可用作PET和SPECT成像的成像剂，以可视化血清素转运蛋白的位置和密度。
• Chen; Kilts; Camp, Journal of labelled compounds and radiopharmaceuticals, 1999, vol. 42, # SUPPL. 1, p. S324-S326
  作者：Chen、Kilts、Camp、Ely、Malveaux、Votaw、Hoffman、Goodman

  DOI：——

  日期：——
• Synthesis and Transporter Binding Properties of 3β-(4‘-Alkyl-, 4‘-alkenyl-, and 4‘-alkynylphenyl)nortropane-2β-carboxylic Acid Methyl Esters:  Serotonin Transporter Selective Analogs
  作者：Bruce E. Blough、Philip Abraham、Anita H. Lewin、Michael J. Kuhar、John W. Boja、F. Ivy Carroll

  DOI：10.1021/jm960409s

  日期：1996.1.1

  New methods for the synthesis of 3 beta-(4'-alkyl-, 4'-alkenyl-, and 4'-alkynylphenyl)nortropane-2 beta-carboxylic acid methyl esters 2-4, respectively, were developed. These methods involved coupling of the appropriate organometallic reagents to 3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (6a, RTI-55) or to an N-protected derivative of 6a followed by N-demethylation or removal of the protecting group. Some analogs were prepared by catalytic reduction of the alkene and alkyne analogs 3 and 4 or by isomerization of the alkenes 3. The analogs 2-4 were evaluated for inhibition of radioligand binding to the serotonin (5-HT), dopamine (DA), and norepinephrine (NE) transporters. 3 beta-(4'-Isopropenyl- and 4'-cis-propenylphenyl)nortropane-2 beta-carboxylic acid methyl esters (3b,d), which possessed IC50 values of 0.6 and 1.15 nM, respectively, were the most potent analogs at the 5-HT transporter, and with NE/5-HT IC50 ratios of 240 and 128 nM, respectively, they were selective for the 5-HT relative to the NE transporter. Since interaction with the serotonin transporter may modulate the pharmacological effects resulting from binding to the dopamine transporter, 3 beta-(4'-isopropenylphenyl)tropane-2 beta-carboxylic acid methyl ester (11b) which has good affinity for both the 5-HT and DA transporters but low affinity at the NE transporter may be useful for studying this interaction.