Cyclohexanecarbothioic acid {2-[4-(2-methoxy-phenyl)-piperazin-1-yl]-ethyl}-amide | 184951-42-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: Cyclohexanecarbothioic acid {2-[4-(2-methoxy-phenyl)-piperazin-1-yl]-ethyl}-amide
• 英文别名: N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl]-cyclohexanecarbothioamide；N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]cyclohexanecarbothioamide
• CAS: 184951-42-6
• 化学式: C₂₀H₃₁N₃OS
• 分子量: 361.552
• InChiKey: MYBOXBVEOOITSF-UHFFFAOYSA-N

物化性质

• 沸点：
  510.2±60.0 °C(Predicted)
• 密度：
  1.116±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  59.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  Rec 0/0249 在 tetraphosphorus decasulfide 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以1.9 g的产率得到Cyclohexanecarbothioic acid {2-[4-(2-methoxy-phenyl)-piperazin-1-yl]-ethyl}-amide
  参考文献：
  名称：

  5-HT_1A- versus D₂-Receptor Selectivity of Flesinoxan and Analogous N ⁴-Substituted N ¹-Arylpiperazines

  摘要：

  We investigated the structural requirements for high 5-HT1A affinity of the agonist flesinoxan and its selectivity versus D-2 receptors. For this purpose a series of arylpiperazine congeners of flesinoxan were synthesized and evaluated for their ability to displace [H-3]-8-OH-DPAT and [H-3]spiperone from their specific binding sites in rat frontal cortex homogenates and rat striatum, respectively. Variations were made in the N-4-substituent and the arylpiperazine region. Effects of N-4-substitution in the investigated compounds appeared to be quite similar for 5-HT1A- and D-2-receptor affinity. Lipophilicity at a distance of four carbon atoms from the piperazine N-4 atom seems to be the main contributing factor to affinity for both receptors. Our data show that the amide group in the flesinoxan N-4-substituent is unlikely to interact with the 5-HT1A receptor but, instead, acts as a spacer. In contrast to the structure-affinity relationships (SARs) of the N-4-substituents, selectivity for 5-HT1A versus D-2 receptors was gained by the arylpiperazine substitution pattern of flesinoxan. Restriction of flexibility of the N-4-(benzoylamino)ethyl substituent and its effect on 5-HT1A-receptor affinity and activity were also studied. Our data show that in the bioactive conformation, the N-4-[(p-fluorobenzoyl)amino]ethyl substituent is probably directed anti-periplanar relative to the H-N4 atom. These results were used to dock flesinoxan (1) and two of its congeners (27 and 33) into a model of the 5-HT1A receptor that we previously reported. Amino acid residues surrounding the N-4-[(p-fluorobenzoyl)amino]ethyl substituent of flesinoxan and its congeners are also present in D-2 receptors. In contrast, several residues that contact the benzodioxane moiety differ from those in D-2 receptors. These observations from the 3D model agree with the 5-HT1A SAR data and probably account for the selectivity of flesinoxan versus D-2 receptors.

  DOI：

  10.1021/jm960496o