RTI 83 | 155337-52-3

• 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: RTI 83
• 英文别名: (-)-2beta-Carbomethoxy-3beta-(4-ethylphenyl)tropane；methyl (1R,2S,3S,5S)-3-(4-ethylphenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 155337-52-3
• 化学式: C₁₈H₂₅NO₂
• 分子量: 287.402
• InChiKey: UAMCGXVVAUEEEU-HZMVEIRTSA-N

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：
  0.61
• 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：

  RTI 83 在 高氯酸 、 碘 、 mercury(II) oxide 作用下， 以 二氯甲烷 、 溶剂黄146 为溶剂， 以34%的产率得到RTI-4229-222
  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 、 氢气 、 zinc(II) chloride 作用下， 以 乙酸乙酯 为溶剂， -78.0~25.0 ℃ 、413.69 kPa 条件下， 反应 26.25h， 生成 RTI 83
  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 of the 2β,3α- and 2β,3β-isomers of 3-(p-substituted phenyl)tropane-2-carboxylic acid methyl esters
  作者：Kathryn I. Keverline、Philip Abraham、Anita H. Lewin、F.Ivy Carroll

  DOI：10.1016/0040-4039(95)00477-t

  日期：1995.5

  The synthesis of 3-(p-substituted phenyl)trop-2-ene-2-carboxylic acid methyl ester 8 and its reduction with samarium iodide provide a new synthesis of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid methyl ester (2) and, in addition, give the first synthesis of the 2 beta,3 alpha-diastereoisomer 4.
• Secondary Amine Analogs of 3.beta.-(4'-Substituted phenyl)tropane-2.beta.-carboxylic Acid Esters and N-Norcocaine Exhibit Enhanced Affinity for Serotonin and Norepinephrine Transporters
  作者：John W. Boja、Michael J. Kuhar、Theresa Kopajtic、Emily Yang、Philip Abraham、Anita H. Lewin、F. Ivy Carroll

  DOI：10.1021/jm00034a021

  日期：1994.4

  N-Norcocaine (2) and six N-nor-3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid esters (4a-f) were synthesized by N-demethylation of cocaine (1) and the appropriate 3 beta-(substituted phenyl)tropane analogues (3a-f) with alpha-chloroethyl chloroformate. Radioligand binding affinities of 2 and 4a-f at the DA, 5-HT, and NE transporter were measured and compared to those of 1 and 3a-f. N-Demethylation produced relatively small effects at the DA transporter. In contrast, 4-19-fold and 2-44-fold enhanced affinity at the serotonin and norepinephrine transporter resulted from demethylation. N-Nor-3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (4d) with an IC50 = 0.36 nM showed the greatest affinity for the serotonin transporter. However, N-nor-3 beta-(4'-ethylphenyl)tropane-2 beta-carboxylic acid methyl ester (4e) showed the greatest selectivity for the serotonin transporter.
• Sandell; Helfenbein; Halldin, Journal of labelled compounds and radiopharmaceuticals, 1999, vol. 42, # SUPPL. 1, p. S51-S53
  作者：Sandell、Helfenbein、Halldin、Chou、Emond、Guilloteau、Farde

  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.