1,3,5-tri[(6',8'β-dimethylergolin-1'-yl)methyl]-2,4,6-trimethylbenzene

• 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: 1,3,5-tri[(6',8'β-dimethylergolin-1'-yl)methyl]-2,4,6-trimethylbenzene
• 英文别名: (6aR,9R,10aR)-4-[[3,5-bis[[(6aR,9R,10aR)-7,9-dimethyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinolin-4-yl]methyl]-2,4,6-trimethylphenyl]methyl]-7,9-dimethyl-6,6a,8,9,10,10a-hexahydroindolo[4,3-fg]quinoline
• 化学式: C₆₀H₇₂N₆
• 分子量: 877.272
• InChiKey: VWPUWBORTDOCGW-ZCSROONKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.4
• 重原子数：
  66
• 可旋转键数：
  6
• 环数：
  13.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  24.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,4,6-三溴甲基三甲基苯 、 6,8beta-二甲基麦角灵 在 氢氧化钾 作用下， 以 二甲基亚砜 为溶剂， 反应 3.0h， 以48%的产率得到1,3,5-tri[(6',8'β-dimethylergolin-1'-yl)methyl]-2,4,6-trimethylbenzene
  参考文献：
  名称：

  In vitro antiplasmodial activities of semisynthetic N,N′-spacer-linked oligomeric ergolines

  摘要：

  Starting from three monomeric ergolines (terguride 1, festuclavine 2, pergolide 3) N,N'-spacer-linked oligomeric derivatives were prepared using different aliphatic or arylalkyl spacers. The compounds have been evaluated for their in vitro anti-plasmodial activity against the chloroquine-sensitive strain poW and the chloroquine-resistant clone Dd2 of Plasmodium falciparum. Additionally, the cytotoxic effects against mouse fibroblasts (NIH 3T3) in vitro, and human hepatocytes were evaluated. All monomers displayed only a weak antiplasmodial effect, but N-1,N-1'-spacer-linked dimerization substantially enhanced their antiplasmodial activity. The best activities were observed for compounds showing a distance of six carbon atoms between two monomers, which can be obtained by aliphatic or p-xylene linkers. The N-6,N-6'-spacer-linked depropylpergolide dimer 3i exhibited the highest antiplasmodial activity of all compounds tested (IC50 values: 0.14 and 0.13 muM against poW and Dd2, respectively). Unfortunately, it displayed toxic effects against the mouse fibroblast cell line NIH 3T3 (IC50: 0.1+/-0.09 muM) and also against human hepatocytes at 100 muM (LDH-leakage: 15.58+/-0.87 mukat/L; GSH-level: 8.15+/-0.78 nmol/10(6) cells). However, the N-1,N-1'-spacer-linked trimer of festuclavine (2f), and also the N-1,N-1-spacer-linked tetramer of terguride (1g) possessed remarkable antiplasmodial activities (IC50: 0.54 and 1.53 muM, respectively, against Dd2) lacking cytotoxicity. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.10.035

文献信息

• In vitro antiplasmodial activities of semisynthetic N,N′-spacer-linked oligomeric ergolines
  作者：Kristina Jenett-Siems、Inga Köhler、Carola Kraft、Heinz H Pertz、Vladimı́r Křen、Anna Fišerová、Marek Kuzma、Jitka Ulrichová、Ulrich Bienzle、Eckart Eich

  DOI：10.1016/j.bmc.2003.10.035

  日期：2004.2

  Starting from three monomeric ergolines (terguride 1, festuclavine 2, pergolide 3) N,N'-spacer-linked oligomeric derivatives were prepared using different aliphatic or arylalkyl spacers. The compounds have been evaluated for their in vitro anti-plasmodial activity against the chloroquine-sensitive strain poW and the chloroquine-resistant clone Dd2 of Plasmodium falciparum. Additionally, the cytotoxic effects against mouse fibroblasts (NIH 3T3) in vitro, and human hepatocytes were evaluated. All monomers displayed only a weak antiplasmodial effect, but N-1,N-1'-spacer-linked dimerization substantially enhanced their antiplasmodial activity. The best activities were observed for compounds showing a distance of six carbon atoms between two monomers, which can be obtained by aliphatic or p-xylene linkers. The N-6,N-6'-spacer-linked depropylpergolide dimer 3i exhibited the highest antiplasmodial activity of all compounds tested (IC50 values: 0.14 and 0.13 muM against poW and Dd2, respectively). Unfortunately, it displayed toxic effects against the mouse fibroblast cell line NIH 3T3 (IC50: 0.1+/-0.09 muM) and also against human hepatocytes at 100 muM (LDH-leakage: 15.58+/-0.87 mukat/L; GSH-level: 8.15+/-0.78 nmol/10(6) cells). However, the N-1,N-1'-spacer-linked trimer of festuclavine (2f), and also the N-1,N-1-spacer-linked tetramer of terguride (1g) possessed remarkable antiplasmodial activities (IC50: 0.54 and 1.53 muM, respectively, against Dd2) lacking cytotoxicity. (C) 2003 Elsevier Ltd. All rights reserved.