N-((S)-1-methylpropyl)-9,10-didehydro-6-methylergoline-8β-carboxamide | 137765-84-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 麦角林及其衍生物
• 英文名称: N-((S)-1-methylpropyl)-9,10-didehydro-6-methylergoline-8β-carboxamide
• 英文别名: (S)-2-butylsergamide；(6aR,9R)-N-[(2S)-butan-2-yl]-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
• CAS: 137765-84-5
• 化学式: C₂₀H₂₅N₃O
• 分子量: 323.438
• InChiKey: NYFSQPDQLFFBRA-WPKBUWHJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  48.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (S)-(+)-2-氨基丁烷 、 麦角酸 在 三氯氧磷 作用下， 以 氯仿 为溶剂， 反应 0.08h， 以91.7%的产率得到N-((S)-1-methylpropyl)-9,10-didehydro-6-methylergoline-8β-carboxamide
  参考文献：
  名称：

  Stereoselective LSD-like activity in d-lysergic acid amides of R- and S-2-aminobutane

  摘要：

  The (R)- and (S)-2-butylamides of d-lysergic acid were prepared and evaluated in behavioral and biochemical assays of 5-HT2 agonist activity. In rats trained to discriminate 0.08 mg/kg LSD tartrate from saline, both isomers completely substituted for the training stimulus. Similarly, both isomers were found to possess very high affinity in displacing [I-125]-(R)-DOI ([I-125]-(R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) from rat cortical homogenate 5-HT2 receptors and in displacing [H-3]-8-OH-DPAT ([H-3]-8-hydroxy-2-(di-n-propylamino)tetralin) from rat hippocampal 5-HT1A receptors. The difference in activity between the two isomeric amides was significant in both the behavioral and binding assays, with the R isomer possessing greater potency. Molecular mechanics were used to predict the active geometries of the subject compounds. It was found that the (R)-2-butylamide has a conformation quite similar to LSD, while the (S)-2-butylamide does not. These results suggest that stereochemical properties of the amide substituent of hallucinogenic lysergamide may exert a critical influence on activity. It is concluded that the conformation of the amide function may directly affect binding through stereoselective interactions with a hydrophobic region on the receptor, indirectly by inducing conformational changes elsewhere in the molecule, or by a combination of these two mechanisms.

  DOI：

  10.1021/jm00080a001

文献信息

• Stereoselective LSD-like activity in d-lysergic acid amides of R- and S-2-aminobutane
  作者：Robert Oberlender、Robert C. Pfaff、Michael P. Johnson、Xuemei Huang、David E. Nichols

  DOI：10.1021/jm00080a001

  日期：1992.1

  The (R)- and (S)-2-butylamides of d-lysergic acid were prepared and evaluated in behavioral and biochemical assays of 5-HT2 agonist activity. In rats trained to discriminate 0.08 mg/kg LSD tartrate from saline, both isomers completely substituted for the training stimulus. Similarly, both isomers were found to possess very high affinity in displacing [I-125]-(R)-DOI ([I-125]-(R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) from rat cortical homogenate 5-HT2 receptors and in displacing [H-3]-8-OH-DPAT ([H-3]-8-hydroxy-2-(di-n-propylamino)tetralin) from rat hippocampal 5-HT1A receptors. The difference in activity between the two isomeric amides was significant in both the behavioral and binding assays, with the R isomer possessing greater potency. Molecular mechanics were used to predict the active geometries of the subject compounds. It was found that the (R)-2-butylamide has a conformation quite similar to LSD, while the (S)-2-butylamide does not. These results suggest that stereochemical properties of the amide substituent of hallucinogenic lysergamide may exert a critical influence on activity. It is concluded that the conformation of the amide function may directly affect binding through stereoselective interactions with a hydrophobic region on the receptor, indirectly by inducing conformational changes elsewhere in the molecule, or by a combination of these two mechanisms.