4-Isobutyl-7-methyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline-9-carboxylic acid | 109839-85-2

• 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: 4-Isobutyl-7-methyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline-9-carboxylic acid
• CAS: 109839-85-2
• 化学式: C₂₀H₂₆N₂O₂
• 分子量: 326.439
• InChiKey: AEGZTHZOMVWMSM-QGPMSJSTSA-N

物化性质

• 沸点：
  530.1±50.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.34
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  45.47
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (2R,3R)-(-)-2,3-丁二醇 、 4-Isobutyl-7-methyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline-9-carboxylic acid 在 对甲苯磺酸 作用下， 生成 (6aR,9R,10aR)-4-Isobutyl-7-methyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline-9-carboxylic acid (1R,2R)-2-hydroxy-1-methyl-propyl ester
  参考文献：
  名称：

  6-Methylergoline-8-carboxylic acid esters as serotonin antagonists: N1-substituent effects on 5HT2 receptor affinity

  摘要：

  Three series of 6-methylergoline-8-carboxylic acid esters with various alkyl substituents in the N1-position were prepared and their 5HT2 receptor affinities measured. Some overlap occurred in the 5HT2 receptor affinities of the different ester series, indicating that both the ester side chain and the indole substituent influenced 5HT2 receptor affinity. While 5HT2 receptor affinity was affected by the structure of the ester side chain, the N1-substituent played a more crucial role in determining 5HT2 receptor affinity. When the ester side chain was held constant, maximal 5HT2 receptor affinity for that series of esters was obtained when the N1-substituent was isopropyl. Smaller substituents in the N1-position resulted in reduced 5HT2 receptor affinity. Groups C4 or larger in the N1-position resulted in a further decline in 5HT2 receptor affinity. The importance of the N1-substituent in determining 5HT2 receptor affinity was further substantiated when several 2-methyl-3-ethyl-5-(dimethylamino)indoles with various N1-substituents were tested. Again, maximal 5HT2 receptor affinity was obtained when the N1-substituent was isopropyl.

  DOI：

  10.1021/jm00393a024
• 作为产物：
  描述：

  邻甲苯磺酸异丁酯 、 9,10-二氢麦角酸 在 氢氧化钾 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 生成 4-Isobutyl-7-methyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline-9-carboxylic acid
  参考文献：
  名称：

  6-Methylergoline-8-carboxylic acid esters as serotonin antagonists: N1-substituent effects on 5HT2 receptor affinity

  摘要：

  Three series of 6-methylergoline-8-carboxylic acid esters with various alkyl substituents in the N1-position were prepared and their 5HT2 receptor affinities measured. Some overlap occurred in the 5HT2 receptor affinities of the different ester series, indicating that both the ester side chain and the indole substituent influenced 5HT2 receptor affinity. While 5HT2 receptor affinity was affected by the structure of the ester side chain, the N1-substituent played a more crucial role in determining 5HT2 receptor affinity. When the ester side chain was held constant, maximal 5HT2 receptor affinity for that series of esters was obtained when the N1-substituent was isopropyl. Smaller substituents in the N1-position resulted in reduced 5HT2 receptor affinity. Groups C4 or larger in the N1-position resulted in a further decline in 5HT2 receptor affinity. The importance of the N1-substituent in determining 5HT2 receptor affinity was further substantiated when several 2-methyl-3-ethyl-5-(dimethylamino)indoles with various N1-substituents were tested. Again, maximal 5HT2 receptor affinity was obtained when the N1-substituent was isopropyl.

  DOI：

  10.1021/jm00393a024

文献信息

• (8.beta.)-6-Methylergoline amide derivatives as serotonin antagonists: N1-substituent effects on vascular 5HT2 receptor activity
  作者：Jerry W. Misner、William L. Garbrecht、Gifford Marzoni、Kathleen R. Whitten、Marlene L. Cohen

  DOI：10.1021/jm00164a029

  日期：1990.2

  A series of (8 beta)-6-methylergoline amide derivatives was synthesized with various alkyl substituents in the N1-position in order to evaluate their effectiveness in blocking vascular 5HT2 receptors. The influence of both the N1 substituent and amide derivative proved to be of great importance on binding affinities to vascular 5HT2 receptors. Within each series of amides, however, maximum affinity was achieved with an N1-isopropyl substituent (14, 18, 26, 38, and 41; all with 2.7-50 times greater affinity than their N1-H analogues), with the exception of two cases (22 and 37) in the cyclohexylamide derivatives wherein N1-methyl equalled the isopropyl in potency. Other than these exceptions, affinities followed the pattern of H less than Me less than Et less than iPr, with potencies falling off with larger alkyl substituents.