methyl (1R,2S,3S,5S)-8-methyl-3-[4-(2-trimethylsilylethynyl)phenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate | 303731-69-3

• 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 (1R,2S,3S,5S)-8-methyl-3-[4-(2-trimethylsilylethynyl)phenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 303731-69-3
• 化学式: C₂₁H₂₉NO₂Si
• 分子量: 355.552
• InChiKey: GFQBPTQTYLHLEM-NMLBUPMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.65
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 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：

  methyl (1R,2S,3S,5S)-8-methyl-3-[4-(2-trimethylsilylethynyl)phenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 3β-(4'-ethynylphenyl)tropane-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：

  (1R,2S,3S,5S)-3-(4-碘苯基)-8-甲基-8-氮杂双环[3.2.1]辛烷-2-羧酸甲酯 、 三甲基乙炔基硅 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 二异丙胺 作用下， 生成 methyl (1R,2S,3S,5S)-8-methyl-3-[4-(2-trimethylsilylethynyl)phenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate
  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