(R)-2-carbomethoxy-3-(4-methylphenyl)-2-tropene | 220455-67-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (R)-2-carbomethoxy-3-(4-methylphenyl)-2-tropene
• 英文别名: (1R)-3-(4-methylphenyl)trop-2-ene-2-carboxylic acid methyl ester；methyl (1R,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate
• CAS: 220455-67-4
• 化学式: C₁₇H₂₁NO₂
• 分子量: 271.359
• InChiKey: BNKYDFUGHNDCCB-DZGCQCFKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 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：

  (R)-2-carbomethoxy-3-(4-methylphenyl)-2-tropene 在 氢氧化钾 、 二苯基膦叠氮化物 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 0.5h， 生成 (1R,5S)-2-Isocyanato-8-methyl-3-p-tolyl-8-aza-bicyclo[3.2.1]oct-2-ene
  参考文献：
  名称：

  Synthesis and Monoamine Transporter Binding Properties of 2,3-Diaryltropanes

  摘要：

  Synthetic procedures were developed for the synthesis of 2 beta,3 beta- and 2 alpha,3 alpha-diaryltropanes. These compounds are analogues of the 3-aryltropane-2 beta-carboxylic acid methyl ester class of monoamine uptake inhibitors, where the 2 beta-carbomethoxy group has been replaced by an aryl group. The compounds were evaluated for inhibition of radioligand binding at the dopamine, norepinephrine, and serotonin transporters (DAT, NET, and 5-HTT, respectively). The results showed that the replacement of the 2 beta-carbomethoxy group in the 3-aryltropane class with a 2 beta-aryl group led to compounds possessing very similar monoamine transporter binding properties. However, the 2 beta,3 beta-diaryltropanes tended to be more potent at the DAT and more selective for the DAT relative to the NET and 5-HTT. One of the most interesting compounds was 3 beta-(4-methylphenyl)-2 beta-(4-methylphenyl)tropane (3d), which showed an IC50 of 1.23 nM at the DAT with 289- and 185-fold selectivity for the DAT relative to the NET and 5-HTT. The 2 alpha,3 alpha-diaryltropanes were much less potent at all three transporters than 2 beta,3 beta-diaryltropanes.

  DOI：

  10.1021/jm0582423
• 作为产物：
  描述：

  (R)-(+)-2-carbomethoxy-3-tropinone 在 四(三苯基膦)钯 、 sodium hexamethyldisilazane 、 cesium fluoride 作用下， 以 四氢呋喃 为溶剂， 反应 7.0h， 生成 (R)-2-carbomethoxy-3-(4-methylphenyl)-2-tropene
  参考文献：
  名称：

  Synthesis and Monoamine Transporter Binding Properties of 2,3-Diaryltropanes

  摘要：

  Synthetic procedures were developed for the synthesis of 2 beta,3 beta- and 2 alpha,3 alpha-diaryltropanes. These compounds are analogues of the 3-aryltropane-2 beta-carboxylic acid methyl ester class of monoamine uptake inhibitors, where the 2 beta-carbomethoxy group has been replaced by an aryl group. The compounds were evaluated for inhibition of radioligand binding at the dopamine, norepinephrine, and serotonin transporters (DAT, NET, and 5-HTT, respectively). The results showed that the replacement of the 2 beta-carbomethoxy group in the 3-aryltropane class with a 2 beta-aryl group led to compounds possessing very similar monoamine transporter binding properties. However, the 2 beta,3 beta-diaryltropanes tended to be more potent at the DAT and more selective for the DAT relative to the NET and 5-HTT. One of the most interesting compounds was 3 beta-(4-methylphenyl)-2 beta-(4-methylphenyl)tropane (3d), which showed an IC50 of 1.23 nM at the DAT with 289- and 185-fold selectivity for the DAT relative to the NET and 5-HTT. The 2 alpha,3 alpha-diaryltropanes were much less potent at all three transporters than 2 beta,3 beta-diaryltropanes.

  DOI：

  10.1021/jm0582423

文献信息

• Synthesis and transporter binding properties of (R)-2β,3β- and (R)-2α,3α-diaryltropanes
  作者：Songchun Jiang、An-Chih Chang、Philip Abraham、Michael J. Kuhar、F.Ivy Carroll

  DOI：10.1016/s0960-894x(98)00673-8

  日期：1998.12

  (R)-2-Aryl-2-tropinone (9) was synthesized from (R)-2-carbomethoxy-3-tropinone (5) and was used as the key intermediate for the synthesis of (R)-2 beta,3 beta- and (R)-2 alpha,3 alpha-diaryltropanes. Inhibition of radioligand binding studies at the dopamine, serotonin, and norepinephrine transporters showed that the (R)-3 beta-(4-methylphenyl)-2 beta-phenyltropane (3b, RTI-422) possessed an IC50 value of 1.96 nM at the dopamine transporter and was highly selective for this transporter relative to the serotonin and norepinephrine transporters. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Monoamine Transporter Binding, Locomotor Activity, and Drug Discrimination Properties of 3-(4-Substituted-phenyl)tropane-2-carboxylic Acid Methyl Ester Isomers
  作者：F. Ivy Carroll、Scott P. Runyon、Philip Abraham、Hernan Navarro、Michael J. Kuhar、Gerald T. Pollard、James L. Howard

  DOI：10.1021/jm0401311

  日期：2004.12.1

  The monoamine transporter binding properties, gross behavior, and locomotor activity effects in mice and drug discrimination results in cocaine-trained rats of the 2beta3beta-, 2beta,3alpha-, 2alpha-,3beta-, and 2alpha-,3alpha-isomers of several 3-(4-substituted-phenyl)tropane carboxylic acid methyl esters were compared (2a-f, 3a-f, 4a-f, and 5b,c). The 2beta,3beta-isomer showed the highest affinity for the dopamine transporter (DAT), and the 2beta,3alpha-isomer showed the next highest affinity. The order of potency for the 2beta,3beta-isomer is 4'-chloro (2c) = 4'-iodo (2e) > 4'-bromo (2d) = 4'-methyl (2f) > 4'-fluoro (2b) > 4'-hydrogen (2a). In the case of the 2beta,3alpha-isomer, the order of affinity was 4'-bromo (3d) > 4'-iodo (3e) = 4'- chloro (3c) > 4'-methyl (3f) > 4'-fluoro (3b) > 4'-hydrogen (3a). The 4'-hydrogen, 4'-fluoro, and 4'-methyl 2alpha,3beta-isomers, 4a, 4b, and 4f, had the lowest affinity for the DAY While most of the compounds showed their highest affinity at the DAT, none were selective relative to the other two monoamine transporters. In general, the 2alpha,3alpha- and 2alpha,3beta-isomers were more toxic (death and convulsions) than the 2beta,3beta- and 2beta,3alpha-isomers. With the exception of the 2(x,3a-isomers, all compounds produced the locomotor activity stimulation typical of dopaminergic drugs. The ED50 ranges for the 2beta,3beta- (2a-f), 2beta,3alpha- (3a-f), and 2alpha,3alpha-isomers (4a-f) in the locomotor assay were 0.1-1.2, 6.6-21.8, and 2.4-11.7 mg/kg, respectively. With the exception of the 2a,3a-isomer, all compounds generalized to cocaine. The 2beta,3beta-isomers were at least 10-fold more potent than cocaine and the other three sets of isomers in this test.
• Synthesis and Monoamine Transporter Binding Properties of 2,3-Diaryltropanes
  作者：Sharadsrikar V. Kotturi、Songchun Jiang、An-Chih Chang、Philip Abraham、Hernán A. Navarro、Michael J. Kuhar、F. Ivy Carroll

  DOI：10.1021/jm0582423

  日期：2005.11.1

  Synthetic procedures were developed for the synthesis of 2 beta,3 beta- and 2 alpha,3 alpha-diaryltropanes. These compounds are analogues of the 3-aryltropane-2 beta-carboxylic acid methyl ester class of monoamine uptake inhibitors, where the 2 beta-carbomethoxy group has been replaced by an aryl group. The compounds were evaluated for inhibition of radioligand binding at the dopamine, norepinephrine, and serotonin transporters (DAT, NET, and 5-HTT, respectively). The results showed that the replacement of the 2 beta-carbomethoxy group in the 3-aryltropane class with a 2 beta-aryl group led to compounds possessing very similar monoamine transporter binding properties. However, the 2 beta,3 beta-diaryltropanes tended to be more potent at the DAT and more selective for the DAT relative to the NET and 5-HTT. One of the most interesting compounds was 3 beta-(4-methylphenyl)-2 beta-(4-methylphenyl)tropane (3d), which showed an IC50 of 1.23 nM at the DAT with 289- and 185-fold selectivity for the DAT relative to the NET and 5-HTT. The 2 alpha,3 alpha-diaryltropanes were much less potent at all three transporters than 2 beta,3 beta-diaryltropanes.