N⁴-(5-(2-fluorophenoxy)-6-methoxy-4-methylquinolin-8-yl)pentane-1,4-diamine | 1361025-59-3

• 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: N⁴-(5-(2-fluorophenoxy)-6-methoxy-4-methylquinolin-8-yl)pentane-1,4-diamine
• 英文别名: 4-N-[5-(2-fluorophenoxy)-6-methoxy-4-methylquinolin-8-yl]pentane-1,4-diamine
• CAS: 1361025-59-3
• 化学式: C₂₂H₂₆FN₃O₂
• 分子量: 383.466
• InChiKey: WPKXVUVSLAOMDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  69.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  丁二酸 、 N⁴-(5-(2-fluorophenoxy)-6-methoxy-4-methylquinolin-8-yl)pentane-1,4-diamine 以 乙醇 为溶剂， 生成 N4-(5-(2-fluorophenoxy)-6-methoxy-4-methylquinolin-8-yl)pentane-1,4-diamine succinate
  参考文献：
  名称：

  Inhibition of human monoamine oxidase A and B by 5-phenoxy 8-aminoquinoline analogs

  摘要：

  8-Aminoquinolines (8-AQs) are important class of anti-infective therapeutics. 5-Phenoxy 8-aminoquinoline analogs have shown improved metabolic stability compared to primaquine. In view or predictive role of monoamine oxidases (MAO) in metabolism of 8-aminoquinolines the 5-phenoxy analogs were evaluated in vitro for the inhibition of recombinant human MAO-A and MAO-B. The analogs were several folds more potent inhibitors of MAO-A and MAO-B compared to primaquine, the parent drug, with selectivity for MAO-B. 5-(4-Trifluoromethylphenoxy)-4-methylprimaquine (6) Inhibited MAO-B with IC50 value of 150 nM (626-fold more potent than primaquine). These results will have important implications in optimizing metabolic stability of 8-AQs to improve therapeutic value and also indicate scope for development of 8-AQs as selective MAO inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.108
• 作为产物：
  描述：

  N-(5-氯-4-甲氧基-2-硝基苯基)乙酰胺 在 盐酸 、 sodium tetrahydroborate 、 磷酸 、 palladium on activated charcoal 、 水 、 一水合肼 、 溶剂黄146 、 potassium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 N⁴-(5-(2-fluorophenoxy)-6-methoxy-4-methylquinolin-8-yl)pentane-1,4-diamine
  参考文献：
  名称：

  Inhibition of human monoamine oxidase A and B by 5-phenoxy 8-aminoquinoline analogs

  摘要：

  8-Aminoquinolines (8-AQs) are important class of anti-infective therapeutics. 5-Phenoxy 8-aminoquinoline analogs have shown improved metabolic stability compared to primaquine. In view or predictive role of monoamine oxidases (MAO) in metabolism of 8-aminoquinolines the 5-phenoxy analogs were evaluated in vitro for the inhibition of recombinant human MAO-A and MAO-B. The analogs were several folds more potent inhibitors of MAO-A and MAO-B compared to primaquine, the parent drug, with selectivity for MAO-B. 5-(4-Trifluoromethylphenoxy)-4-methylprimaquine (6) Inhibited MAO-B with IC50 value of 150 nM (626-fold more potent than primaquine). These results will have important implications in optimizing metabolic stability of 8-AQs to improve therapeutic value and also indicate scope for development of 8-AQs as selective MAO inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.108

文献信息

• 10.1016/j.bioorg.2024.107472
  作者：Manen-Freixa, Leticia、Moliner-Cubel, Sonia、Gamo, Francisco-Javier、Crespo, Benigno、Borrell, José I.、Teixidó, Jordi、Estrada-Tejedor, Roger

  DOI：10.1016/j.bioorg.2024.107472

  日期：——

  to illustrate the process. Through the deep exploration of the Tafenoquine chemical space, seven compounds with potential antimalarial activity have been rationally identified and synthesized. This small set is representative of the chemical diversity unexplored by the 58 analogs reported to date. After biological assessment, results evidence that our approach for rational design has proven to be a

  专利倾向于定义由马库什结构的组合性质描述的巨大化学空间。然而，新主要活性成分的优化通常是由简单的 Free Wilson 方法驱动的。这一过程导致对命中化合物附近的化学空间进行高度集中的研究，留下许多可能存在高度生物活性储层的未探索区域。这项研究旨在证明，这种公开的化学空间可以隐藏具有值得研究的有趣潜在生物活性的化合物。这强调了拓宽传统策略之外的方法的价值和必要性。因此，我们主张采用一种在早期药物发现阶段可能更有效的替代方法。我们选择2018年FDA批准的单剂量根治疟疾药物他非诺喹的案例来说明这一过程。通过对他非诺喹化学空间的深入探索，合理鉴定并合成了七种具有潜在抗疟活性的化合物。这一小组代表了迄今为止报道的 58 种类似物尚未探索的化学多样性。经过生物学评估，结果证明我们的合理设计方法已被证明是一种非常有效的探索性方法，适合早期药物发现阶段。
• Inhibition of human monoamine oxidase A and B by 5-phenoxy 8-aminoquinoline analogs
  作者：Narayan D. Chaurasiya、Shobana Ganesan、N.P. Dhammika Nanayakkara、Luiza R.S. Dias、Larry A. Walker、Babu L. Tekwani

  DOI：10.1016/j.bmcl.2011.12.108

  日期：2012.2

  8-Aminoquinolines (8-AQs) are important class of anti-infective therapeutics. 5-Phenoxy 8-aminoquinoline analogs have shown improved metabolic stability compared to primaquine. In view or predictive role of monoamine oxidases (MAO) in metabolism of 8-aminoquinolines the 5-phenoxy analogs were evaluated in vitro for the inhibition of recombinant human MAO-A and MAO-B. The analogs were several folds more potent inhibitors of MAO-A and MAO-B compared to primaquine, the parent drug, with selectivity for MAO-B. 5-(4-Trifluoromethylphenoxy)-4-methylprimaquine (6) Inhibited MAO-B with IC50 value of 150 nM (626-fold more potent than primaquine). These results will have important implications in optimizing metabolic stability of 8-AQs to improve therapeutic value and also indicate scope for development of 8-AQs as selective MAO inhibitors. (C) 2012 Elsevier Ltd. All rights reserved.