N-(8-(furan-2-ylmethyl)-8-azabicyclo[3.2.1]oct-3β-yl)-3,4,5-trimethoxybenzamide | 1335036-45-7

• 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: N-(8-(furan-2-ylmethyl)-8-azabicyclo[3.2.1]oct-3β-yl)-3,4,5-trimethoxybenzamide
• CAS: 1335036-45-7
• 化学式: C₂₂H₂₈N₂O₅
• 分子量: 400.475
• InChiKey: MYJZXJWVQVVYHK-OSYLJGHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.23
• 重原子数：
  29.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  73.17
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  8-(furan-2-ylmethyl)-8-azabicyclo[3.2.1]octan-3-one 在 盐酸羟胺 、 sodium 、 氯甲酸乙酯 、 碳酸氢钠 、 三乙胺 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 N-(8-(furan-2-ylmethyl)-8-azabicyclo[3.2.1]oct-3β-yl)-3,4,5-trimethoxybenzamide
  参考文献：
  名称：

  Synthesis and biological investigation of potential atypical antipsychotics with a tropane core. Part 1

  摘要：

  The synthesis, structure, in vitro and in vivo pharmacological activities of 3 beta-acylamine derivatives of tropane (4a-n, 5a-g, 6a,b, 8a-c) are described.Among the investigated compounds, several displayed very high (in nM) affinity for the monoamine receptors 5-HT1A, 5-HT2A, and D-2.The most interesting agent 6b revealed very high affinity for the 5-HT2A and D-2 receptors and high affinity for the 5-HT1A receptor. The in vivo head twitch model was used to demonstrate antagonism of the 5-HT2A receptor subtype by this compound. In another test, 6b caused hypothermia in mice, which was not attenuated by WAY 100635. In the climbing test, the compound did not significantly modify climbing behaviour following apomorphine administration. Moreover, 6b significantly reduced locomotor activity in mice.Molecular docking studies using a homology model of the 5-HT1A receptor revealed a significant role of the N-8 atom of the tropane core in stabilising the ligand receptor complex due to strong hydrogen bonding with Asp116 located in the TMH 3 helix. Analogically, in a homology model of the 5-HT2A receptor, the N-8 atom formed a hydrogen bond with Gly369. In another homology model of the D-2 receptor, strong hydrogen bonding of the amide moiety in the 3 beta position of the tropane nucleus with Asp85 was observed. Compound 6b displayed a favourable Meltzer index (1.21) which is a feature of atypical antipsychotic agents. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.07.022