O-Cyclopropanoyl-lysergol | 85892-96-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: O-Cyclopropanoyl-lysergol
• 英文别名: [(6aR,9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]methyl cyclopropanecarboxylate
• CAS: 85892-96-2
• 化学式: C₂₀H₂₂N₂O₂
• 分子量: 322.407
• InChiKey: FENFMNWXCOWGNY-KZULUSFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  45.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-碘代丙烷 、 O-Cyclopropanoyl-lysergol 在 氢氧化钾 、 18-冠醚-6 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 Cyclopropanecarboxylic acid (6aR,9R)-4-isopropyl-7-methyl-4,6,6a,7,8,9-hexahydro-indolo[4,3-fg]quinolin-9-ylmethyl ester
  参考文献：
  名称：

  Cycloalkanecarboxylic Esters Derived from Lysergol, Dihydrolysergol-I, and Elymoclavine as Partial Agonists and Antagonists at Rat 5-HT_2A Receptors:  Pharmacological Evidence that the Indolo[4,3-fg]quinoline System of the Ergolines Is Responsible for High 5-HT_2A Receptor Affinity

  摘要：

  Three series of cycloalkanecarboxylic esters derived from the naturally occurring clavine alkaloids lysergol, dihydrolysergol-I, and elymoclavine were synthesized to study their interaction with 5-HT2A receptors and alpha(1)-adrenoceptors in rat tail artery and aorta, respectively. Especially cycloalkanecarboxylic esters derived from lysergol showed complex behavior as partial agonists and antagonists of the contractile effect of 5-HT. Within this group, partial 5-HT2A receptor agonist activity was most potent for cyclopropane carboxylic ester 6a (pK(p) = 7.67, alpha = 0.21) and decreased as the volume requirement of the alicyclic ring increased. This tendency was echoed in experiments where the compounds were used as antagonists of the contractile effect of 5-HT. From the structure-activity study, the N-1-isopropyl homologue of 6a, compound 6b, emerged as the ligand with the highest affinity for rat 5-HT2A receptors (pA(2) = 8.74). For cycloalkanecarboxylic esters derived from dihydrolysergol-I and elymoclavine, no clear structure-affinity relationship could be deduced, although those compounds that had smaller cycloalkyl rings in the acyl portion and an isopropyl substituent at N-1 showed the highest 5-HT2A receptor affinity. On the other hand, cycloalkanecarboxylic esters derived from lysergol, dihydrolysergol-I, and elymoclavine displayed low or marginal affinity at alpha(1)-adrenoceptors, A further aim of the study was to examine to what extent the complete removal of the acyl portion of the esters would affect 5-HT2A receptor affinity. The parent alcohols of the three series of N-1-isopropyl homologues, 1-isopropyllysergol (1b), 1-isopropyldihydrolysergol-I (2b), and 1-isopropylelymoclavine (3b), displayed higher affinity for 5-HT2A receptors (pA(2) = 9.15, 8.50, 9.14) than the corresponding esters. Compounds 1b-3b had no contractile effects by themselves and displayed low affinity at guinea-pig 5-HT1B receptors and rat alpha(1)-adrenoceptors. The high affinity for rat 5-HT2A receptors was retained when clavines even more simple in structure than 1b-3b, compounds 4b and 5b, were examined as 5-HT2A receptor antagonists. The nanomolar antagonist activity of simple clavines (1b-5b) in the rat suggests that the indolo[4,3-wfg]quinoline system of the ergolines is the molecular fragment that is responsible for 5-HT2A receptor affinity, and not the substituent at position C-8.

  DOI：

  10.1021/jm981092u
• 作为产物：
  描述：

  环丙基甲酰氯 、 麦角醇 在 吡啶 作用下， 生成 O-Cyclopropanoyl-lysergol
  参考文献：
  名称：

  从 clavine 生物碱部分合成新的麦角碱衍生物，第 2 版。1) O-acyl-8-hydroxymethyl-6-methylergol-8-enes 和 -ergol-9-enes

  摘要：

  标题化合物可以通过用酰氯酰化草甘膦 (1) 或麦角醇 (2) 来制备，在 2 的酯的情况下，也可以通过 O-酰基-1 与活化的 Al2O3 异构化来制备。相反，在某些情况下，2 的酰化会导致 1 和 2 的 O-酰基衍生物的混合物自发形成。

  DOI：

  10.1002/ardp.19833160404

文献信息

• Partialsynthese neuer Ergolinderivate aus Clavinalkaloiden, 2. Mitt.1) O-Acyl-8-hydroxymethyl-6-methylergol-8-ene und -ergol-9-ene
  作者：Eckart Eich

  DOI：10.1002/ardp.19833160404

  日期：——

  Die Titelverbindungen sind durch Acylierung von Elymoclavin (1) bzw. Lysergol (2) mit Säurechloriden, im Fall der Ester von 2 auch durch Isomerisierung von O‐Acyl‐1 mit aktiviertem Al2O3 darstellbar. Umgekehrt führt die Acylierung von 2 in bestimmten Fällen spontan zur Bildung eines Gemisches der O‐Acylderivate von 1 und 2..

  标题化合物可以通过用酰氯酰化草甘膦 (1) 或麦角醇 (2) 来制备，在 2 的酯的情况下，也可以通过 O-酰基-1 与活化的 Al2O3 异构化来制备。相反，在某些情况下，2 的酰化会导致 1 和 2 的 O-酰基衍生物的混合物自发形成。
• Cycloalkanecarboxylic Esters Derived from Lysergol, Dihydrolysergol-I, and Elymoclavine as Partial Agonists and Antagonists at Rat 5-HT_2A Receptors:  Pharmacological Evidence that the Indolo[4,3-<i>fg</i>]quinoline System of the Ergolines Is Responsible for High 5-HT_2A Receptor Affinity
  作者：Heinz H. Pertz、H.-Christian Milhahn、Eckart Eich

  DOI：10.1021/jm981092u

  日期：1999.2.1

  Three series of cycloalkanecarboxylic esters derived from the naturally occurring clavine alkaloids lysergol, dihydrolysergol-I, and elymoclavine were synthesized to study their interaction with 5-HT2A receptors and alpha(1)-adrenoceptors in rat tail artery and aorta, respectively. Especially cycloalkanecarboxylic esters derived from lysergol showed complex behavior as partial agonists and antagonists of the contractile effect of 5-HT. Within this group, partial 5-HT2A receptor agonist activity was most potent for cyclopropane carboxylic ester 6a (pK(p) = 7.67, alpha = 0.21) and decreased as the volume requirement of the alicyclic ring increased. This tendency was echoed in experiments where the compounds were used as antagonists of the contractile effect of 5-HT. From the structure-activity study, the N-1-isopropyl homologue of 6a, compound 6b, emerged as the ligand with the highest affinity for rat 5-HT2A receptors (pA(2) = 8.74). For cycloalkanecarboxylic esters derived from dihydrolysergol-I and elymoclavine, no clear structure-affinity relationship could be deduced, although those compounds that had smaller cycloalkyl rings in the acyl portion and an isopropyl substituent at N-1 showed the highest 5-HT2A receptor affinity. On the other hand, cycloalkanecarboxylic esters derived from lysergol, dihydrolysergol-I, and elymoclavine displayed low or marginal affinity at alpha(1)-adrenoceptors, A further aim of the study was to examine to what extent the complete removal of the acyl portion of the esters would affect 5-HT2A receptor affinity. The parent alcohols of the three series of N-1-isopropyl homologues, 1-isopropyllysergol (1b), 1-isopropyldihydrolysergol-I (2b), and 1-isopropylelymoclavine (3b), displayed higher affinity for 5-HT2A receptors (pA(2) = 9.15, 8.50, 9.14) than the corresponding esters. Compounds 1b-3b had no contractile effects by themselves and displayed low affinity at guinea-pig 5-HT1B receptors and rat alpha(1)-adrenoceptors. The high affinity for rat 5-HT2A receptors was retained when clavines even more simple in structure than 1b-3b, compounds 4b and 5b, were examined as 5-HT2A receptor antagonists. The nanomolar antagonist activity of simple clavines (1b-5b) in the rat suggests that the indolo[4,3-wfg]quinoline system of the ergolines is the molecular fragment that is responsible for 5-HT2A receptor affinity, and not the substituent at position C-8.