2β-carbomethoxy-3β-(4'-isopropylphenyl)tropane | 181796-44-1

• 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: 2β-carbomethoxy-3β-(4'-isopropylphenyl)tropane
• 英文别名: methyl (1R,2S,3S,5S)-8-methyl-3-(4-propan-2-ylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 181796-44-1
• 化学式: C₁₉H₂₇NO₂
• 分子量: 301.429
• InChiKey: LYCULYABSZPOPO-MLHJIOFPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 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：

  2β-carbomethoxy-3β-(4'-isopropylphenyl)tropane 在 高氯酸 、 碘 、 mercury(II) oxide 作用下， 以 二氯甲烷 、 溶剂黄146 为溶剂， 以76%的产率得到2β-carbomethoxy-3β-(3'-iodo-4'-isopropylphenyl)tropane
  参考文献：
  名称：

  [11C]2?-carbomethoxy-3?-(3?-iodo-4?-methyl,-ethyl andisopropyl phenyl)nortropane 作为潜在放射性示踪剂的合成，用于用正电子发射断层扫描检查血清素转运蛋白

  摘要：

  抑郁症和焦虑症的研究将受益于开发合适的放射性配体，用于 5-羟色胺转运蛋白的 PET 成像。三种可卡因类似物 2β-carbomethoxy-3β-(3'-iodo-4'-methyl, -ethyl and isopropyl phenyl)nortropane（LBT-14、EINT 和 LBT-44）通过三步合成制备-4 作为第一步，将合适的格氏试剂加入到脱水芽子碱甲酯中。苯环的碘化是用黄色氧化汞、高氯酸和乙酸的混合物，然后用碘的二氯甲烷溶液完成的。N-去甲基化是通过使用 2,2,2-三氯乙基氯甲酸酯然后在乙酸中处理锌来进行的。酯官能团的酸水解得到LBT-14、EINT和LBT-44的羧酸类似物。使用 [11C] 甲基碘或 [11C] 三氟甲磺酸甲酯的二甲基甲酰胺 (DMF) 和四丁基氢氧化铵 (TBAH) 作为碱，用 11C 标记前体。[11C]LBT-14、[11C]EINT 和[11C]LBT-44

  DOI：

  10.1002/1099-1344(200009)43:10<1033::aid-jlcr389>3.0.co;2-5
• 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 在 palladium on activated charcoal bis-triphenylphosphine-palladium(II) chloride 、 正丁基锂 、 氢气 、 zinc(II) chloride 作用下， 以 乙醇 为溶剂， 反应 26.0h， 生成 2β-carbomethoxy-3β-(4'-isopropylphenyl)tropane
  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

文献信息

• Synthesis of [11C]2?-carbomethoxy-3?-(3?-iodo-4?-methyl, -ethyl and isopropyl phenyl)nortropane as potential radiotracers for examination of the serotonin transporter with positron emission tomography
  作者：Johan Sandell、Christer Halldin、Julie Helfenbein、Yuan-Hwa Chou、Johnny Vercouillie、Patrick Emond、Carl-Gunnar Swahn、Denis Guilloteau、Lars Farde

  DOI：10.1002/1099-1344(200009)43:10<1033::aid-jlcr389>3.0.co;2-5

  日期：2000.9

  perchloric acid and acetic acid followed by a solution of iodine in dichloromethane. N-desmethylation was performed by using 2,2,2-trichloroethylchloroformiate followed by treatment of zinc in acetic acid. Acidic hydrolysis of the ester functions gave the carboxylic acid analogues of LBT-14, EINT and LBT-44. The precursors were labelled with 11C using [11C]methyl iodide or [11C] methyl triflate in

  抑郁症和焦虑症的研究将受益于开发合适的放射性配体，用于 5-羟色胺转运蛋白的 PET 成像。三种可卡因类似物 2β-carbomethoxy-3β-(3'-iodo-4'-methyl, -ethyl and isopropyl phenyl)nortropane（LBT-14、EINT 和 LBT-44）通过三步合成制备-4 作为第一步，将合适的格氏试剂加入到脱水芽子碱甲酯中。苯环的碘化是用黄色氧化汞、高氯酸和乙酸的混合物，然后用碘的二氯甲烷溶液完成的。N-去甲基化是通过使用 2,2,2-三氯乙基氯甲酸酯然后在乙酸中处理锌来进行的。酯官能团的酸水解得到LBT-14、EINT和LBT-44的羧酸类似物。使用 [11C] 甲基碘或 [11C] 三氟甲磺酸甲酯的二甲基甲酰胺 (DMF) 和四丁基氢氧化铵 (TBAH) 作为碱，用 11C 标记前体。[11C]LBT-14、[11C]EINT 和[11C]LBT-44
• 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.
• Synthesis of Tropane and Nortropane Analogues with Phenyl Substitutions as Serotonin Transporter Ligands
  作者：Patrick Emond、Julie Helfenbein、Sylvie Chalon、Lucette Garreau、Johnny Vercouillie、Yves Frangin、Jean Claude Besnard、Denis Guilloteau

  DOI：10.1016/s0968-0896(01)00083-9

  日期：2001.7

  The effects of structural modifications of 2 beta -carbomethoxy-3 beta -phenyl tropane analogues were evaluated on in vitro affinity to the dopamine (DAT) and serotonin (5-HTT) transporters in rat brain tissue. The introduction of a large alkyl group at the 4'-position of the phenyl ring, affording 2 beta -carbomethoxy-3 beta-(4'-alkylphenyl) tropane, diminished the affinity for the DAT whereas moderate 5-HTT affinity was obtained. The introduction of an iodine at the 3'-position of the 4'-alkylphenyl. affording 2 beta -carbomethoxy-3 beta-(3'-iodo-4'-alkylphenyl) tropane, and N-demethylation, affording 2 beta -carbomethoxy-3 beta-(3'-iodo-4'-alkylphenyl) nortropane. improved affinity and specificity for the 5-HTT. It could be assumed from these results that the combination of these three modifications of tropane structure yielded highly selective compounds for the 5-HTT. Of the new compounds synthesized, the most selective cocaine derivative, 2 beta -carbomethoxy-3 beta-(3'-iodo-4'-isopropylphenyl) nortropane (8d) labeled with iodine-123 or carbon-11, could be a potential ligand for exploration of the 5-HT transporter by SPET or PET. (C) 2001 Published by Elsevier Science Ltd.