(1R,5S)-2-Isocyanato-8-methyl-3-p-tolyl-8-aza-bicyclo[3.2.1]oct-2-ene | 220455-68-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1R,5S)-2-Isocyanato-8-methyl-3-p-tolyl-8-aza-bicyclo[3.2.1]oct-2-ene
• 英文别名: (1R,5S)-2-isocyanato-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]oct-2-ene
• CAS: 220455-68-5
• 化学式: C₁₆H₁₈N₂O
• 分子量: 254.332
• InChiKey: ASXJAJQQRKGVBZ-DZGCQCFKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,5S)-2-Isocyanato-8-methyl-3-p-tolyl-8-aza-bicyclo[3.2.1]oct-2-ene 在 palladium on activated charcoal 盐酸 、 lithium aluminium tetrahydride 、 四(三苯基膦)钯 、 sodium hydride 、 碳酸氢钠 、 cesium fluoride 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， -78.0~20.0 ℃ 、344.74 kPa 条件下， 反应 11.0h， 生成 3α-(4'-methyphenyl)-2α-(3,4-dimethoxyphenyl)tropane
  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beta-carboxylic acid methyl ester class of monoamine uptake inhibitors, where the 2 beta-carbomethoxy group has been replaced by an aryl group.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-(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

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.