8-Azabicyclo[3.2.1]octan-2-one, 8-methyl-3-(4-methylphenyl)-, (1R,5S)- | 220455-69-6

• 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: 8-Azabicyclo[3.2.1]octan-2-one, 8-methyl-3-(4-methylphenyl)-, (1R,5S)-
• 英文别名: (R)-3-(4-methylphenyl)-2-tropinone
• CAS: 220455-69-6
• 化学式: C₁₅H₁₉NO
• 分子量: 229.322
• InChiKey: GKWONPXJUWFPPH-SMEJFCCLSA-N

物化性质

• 熔点：
  100-101.5 °C
• 沸点：
  356.7±42.0 °C(Predicted)
• 密度：
  1.087±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.51
• 重原子数：
  17.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  20.31
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  8-Azabicyclo[3.2.1]octan-2-one, 8-methyl-3-(4-methylphenyl)-, (1R,5S)- 在 palladium on activated charcoal lithium aluminium tetrahydride 、 氢溴酸 、 碳酸氢钠 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 反应 182.25h， 生成 (R)-3α-(methylphenyl)-2α-phenyltropane
  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beta-carboxylic acid methyl ester class of monoamine uptake inhibitors, where the 2 beta-carbomethoxy group has been replaced by an aryl group.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：

  ((1R,5S)-8-Methyl-3-p-tolyl-8-aza-bicyclo[3.2.1]oct-2-en-2-yl)-carbamic acid ethyl ester 在 盐酸 作用下， 反应 1.0h， 生成 8-Azabicyclo[3.2.1]octan-2-one, 8-methyl-3-(4-methylphenyl)-, (1R,5S)-
  参考文献：
  名称：

  Synthesis and transporter binding properties of (R)-2β,3β- and (R)-2α,3α-diaryltropanes

  摘要：

  (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.

  DOI：

  10.1016/s0960-894x(98)00673-8