Rec 0/0249 | 100640-32-2

• 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: Rec 0/0249
• 英文别名: N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]cyclohexanecarboxamide
• CAS: 100640-32-2
• 化学式: C₂₀H₃₁N₃O₂
• 分子量: 345.485
• InChiKey: HJFABTUBWNFTBH-UHFFFAOYSA-N

物化性质

• 沸点：
  557.0±50.0 °C(Predicted)
• 密度：
  1.093±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 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：
  44.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  [4-(2-methoxyphenyl)piperazin-1-yl]acetonitrile 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 生成 Rec 0/0249
  参考文献：
  名称：

  Wilson, Alan A.; DaSilva, Jean N.; Inaba, T., Journal of labelled compounds and radiopharmaceuticals, 1997, vol. 40, p. 531 - 533

  摘要：

  DOI：

文献信息

• Structure-Activity Relationship Studies of CNS Agents, Part 26 4-[2-(Cycloalkanecarboxamido)ethyl]-1-(2-methoxyphenyl)-piperazines: High-Affinity 5-HT1A Agonists
  作者：Jerzy L. Mokrosz、Maria H. Paluchowska、Aleksandra Klodzińska、Sijka Charakchieva-Minol、Ewa Chojnacka-Wójcik

  DOI：10.1002/ardp.19953281108

  日期：——

  Cycloalkanecarboxamido)ethyl‐1‐(2‐methoxyphenyl)piperazin es 8a–c, 8e, and 8h were obtained by acylation of 4‐(2‐aminoethyl)‐1‐(2‐methoxyphenyl)piperazine, and their 5‐HT1A, 5‐HT1A, 5‐HT2A and α receptor affinities were determined. It was found that the terminal cycloalkane moiety strongly stabilizes both the 5‐HT1A and 5‐HT2A receptor‐ligand complexes. It was demonstrated that the most active 5‐HT1A

  环烷甲酰胺基)乙基-1-(2-甲氧基苯基)哌嗪es 8a-c、8e和8h是通过4-(2-氨基乙基)-1-(2-甲氧基苯基)哌嗪和它们的5-HT1A,5酰化得到的测定了-HT1A、5-HT2A和α受体亲和力。发现末端环烷烃部分强烈稳定 5-HT1A 和 5-HT2A 受体-配体复合物。结果表明，最活跃的 5-HT1A 配体 8e 和 8h（分别为 Ki = 2.1 和 0.21 nM）充当这些受体的有效激动剂，即这两种衍生物在下唇收缩 (LLR) 模型中都模拟了 8-OH-DPAT并且该作用易于被合理剂量的选择性 5-HT1A 受体拮抗剂 (S)-WAY-100135 阻断。
• NAGANO, XIROYUKI;TAKAGI, MITIO;KUBODEHRA, NOBORU;MATSUNAGA, ISAO;NABATA, +
  作者：NAGANO, XIROYUKI、TAKAGI, MITIO、KUBODEHRA, NOBORU、MATSUNAGA, ISAO、NABATA, +

  DOI：——

  日期：——
• 5-HT_1A- versus D₂-Receptor Selectivity of Flesinoxan and Analogous <i>N</i> ⁴-Substituted <i>N</i> ¹-Arylpiperazines
  作者：Wilma Kuipers、Chris G. Kruse、Ineke van Wijngaarden、Piet J. Standaar、Martin Th. M. Tulp、Nora Veldman、Anthony L. Spek、Adriaan P. IJzerman

  DOI：10.1021/jm960496o

  日期：1997.1.1

  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.
• Wilson, Alan A.; DaSilva, Jean N.; Inaba, T., Journal of labelled compounds and radiopharmaceuticals, 1997, vol. 40, p. 531 - 533
  作者：Wilson, Alan A.、DaSilva, Jean N.、Inaba, T.、Fischer, N.、Houle, S.

  DOI：——

  日期：——