3β-(4-methylphenyl)-2β-[3'-(4-methylbenzyl)isoxazol-5-yl]tropane | 1061288-59-2

• 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: 3β-(4-methylphenyl)-2β-[3'-(4-methylbenzyl)isoxazol-5-yl]tropane
• CAS: 1061288-59-2
• 化学式: C₂₆H₃₀N₂O
• 分子量: 386.537
• InChiKey: IAMKFWCUQGPZKF-WSKLTFMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.62
• 重原子数：
  29.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  29.27
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  p-Methylbenzylmethylketonoxim 、 (1R,2S,3S,5S)-8-甲基-3-(4-甲基苯基)-8-氮杂双环[3.2.1]辛烷-2-羧酸甲酯 在 正丁基锂 、 盐酸 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 8.0h， 以39%的产率得到3β-(4-methylphenyl)-2β-[3'-(4-methylbenzyl)isoxazol-5-yl]tropane
  参考文献：
  名称：

  Synthesis and monoamine transporter binding properties of 2β-[3′-(substituted benzyl)isoxazol-5-yl]- and 2β-[3′-methyl-4′-(substituted phenyl)isoxazol-5-yl]-3β-(substituted phenyl)tropanes

  摘要：

  A series of 2 beta-[3'-(substituted benzyl)isoxazol-5-yl]- and 2 beta-[3'-methyl-4'-(substituted phenyl)isoxazol-5- yl]-3 beta-(substituted phenyl)tropanes were prepared and evaluated for affinities at dopamine, serotonin, and norepinephrine transporters using competitive radioligand binding assays. The 2 beta-[3'-(substituted benzyl)isoxazol-5-yl]-3 beta-(substituted phenyl)tropanes (3a-h) showed high binding affinities for the dopamine transporter (DAT). The IC50 values ranged from 5.9 to 22 nM. On the other hand, the 2 beta-[3'-methyl- 4'-(substituted phenyl)isoxazol-5-yl]-3 beta-(substituted phenyl)tropanes (4a-h), with IC50 values ranging from 65 to 173 nM, were approximately 3- to 25-fold less potent than the corresponding 2 beta-[ 3'-(substituted benzyl)isoxazol] tropanes. All tested compounds were selective for the DAT relative to the norepinephrine transporter (NET) and serotonin transporter (5-HTT). 3 beta-(4-Methylphenyl)-2 beta-[3'-(4-fluorobenzyl)isoxazol-5-yl] tropane (3b) with IC50 of 5.9 nM at the DAT and K(i)s of 454 and 113 nM at the NET and 5-HTT, respectively, was the most potent and DAT-selective analog. Molecular modeling studies suggested that the rigid conformation of the isoxazole side chain in 4a-h might play an important role on their low DAT binding affinities. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.073