(6aR,9R)-7-Isopropyl-4,6,6a,7,8,9-hexahydro-indolo[4,3-fg]quinoline-9-carboxylic acid diethylamide | 96930-86-8

• 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: (6aR,9R)-7-Isopropyl-4,6,6a,7,8,9-hexahydro-indolo[4,3-fg]quinoline-9-carboxylic acid diethylamide
• 英文别名: (6aR,9R)-N,N-diethyl-7-propan-2-yl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
• CAS: 96930-86-8
• 化学式: C₂₂H₂₉N₃O
• 分子量: 351.492
• InChiKey: GLNOSFGSNDKLOC-OXQOHEQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  39.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  麦角乙二胺 在 potassium carbonate 、 锌 作用下， 以 四氯化碳 、 氯仿 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 154.0h， 生成 (6aR,9R)-7-Isopropyl-4,6,6a,7,8,9-hexahydro-indolo[4,3-fg]quinoline-9-carboxylic acid diethylamide
  参考文献：
  名称：

  Synthesis and LSD-like discriminative stimulus properties in a series of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives

  摘要：

  A convenient method for the synthesis of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives was developed. A series of these compounds was synthesized and tested for substitution in the two-lever drug discrimination assay, in rats trained to discriminate injections of d-LSD tartrate (185.5 nmol/kg, ip) from saline. A dose-response curve for each of the compounds in the series was generated. Structure-activity relationships were developed, based on comparison of the estimated ED50 values from these curves. Of the compounds that substituted for LSD, the N(6)-ethyl and -allyl were approximately 2-3 times more potent than LSD itself. The N(6)-propyl was equipotent to LSD, while the isopropyl derivative was half as active. The n-butyl compound was 1 order of magnitude less potent than LSD, suggesting a similarity to the SAR of certain serotonin and dopamine agonists. By contrast, no generalization occurred to norlysergic acid N,N-diethylamide and the N(6)-2-phenethyl derivative.

  DOI：

  10.1021/jm00147a022

文献信息

• [EN] NOVEL ERGOLINES AND METHODS OF TREATING MOOD DISORDERS<br/>[FR] NOUVELLES ERGOLINES ET PROCÉDÉS DE TRAITEMENT DE TROUBLES DE L'HUMEUR
  申请人：[en]GILGAMESH PHARMACEUTICALS, INC.

  公开号：WO2022226408A1

  公开（公告）日：2022-10-27

  The present disclosure provides ergoline compounds and their use in treating mood disorders. Pharmaceutical compositions and methods of making various ergoline compounds are provided.
• Synthesis and LSD-like discriminative stimulus properties in a series of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives
  作者：Andrew J. Hoffman、David E. Nichols

  DOI：10.1021/jm00147a022

  日期：1985.9

  A convenient method for the synthesis of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives was developed. A series of these compounds was synthesized and tested for substitution in the two-lever drug discrimination assay, in rats trained to discriminate injections of d-LSD tartrate (185.5 nmol/kg, ip) from saline. A dose-response curve for each of the compounds in the series was generated. Structure-activity relationships were developed, based on comparison of the estimated ED50 values from these curves. Of the compounds that substituted for LSD, the N(6)-ethyl and -allyl were approximately 2-3 times more potent than LSD itself. The N(6)-propyl was equipotent to LSD, while the isopropyl derivative was half as active. The n-butyl compound was 1 order of magnitude less potent than LSD, suggesting a similarity to the SAR of certain serotonin and dopamine agonists. By contrast, no generalization occurred to norlysergic acid N,N-diethylamide and the N(6)-2-phenethyl derivative.