1-(5-(2-phenyl-4-chlorophenyl)furan-2-yl)-N-(piperidin-4-ylmethyl)methanamine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(5-(2-phenyl-4-chlorophenyl)furan-2-yl)-N-(piperidin-4-ylmethyl)methanamine
• 英文别名: N-[[5-(4-chloro-2-phenylphenyl)furan-2-yl]methyl]-1-piperidin-4-ylmethanamine
• 化学式: C₂₃H₂₅ClN₂O
• 分子量: 380.917
• InChiKey: BGGHSRZVZYUMIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  37.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-BOC-4-甲磺酰基氧甲基哌啶 在 甲醇 、 sodium tetrahydroborate 、 sodium azide 、 palladium 10% on activated carbon 、 氢气 、 乙酰氯 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 90.0 ℃ 、101.33 kPa 条件下， 反应 32.0h， 生成 1-(5-(2-phenyl-4-chlorophenyl)furan-2-yl)-N-(piperidin-4-ylmethyl)methanamine
  参考文献：
  名称：

  Antimalarial agents against both sexual and asexual parasites stages: structure-activity relationships and biological studies of the Malaria Box compound 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine (MMV019918) and analogues

  摘要：

  Therapies addressing multiple stages of Plasmodium falciparum life cycle are highly desirable for implementing malaria elimination strategies. MMV019918 (1, 1-[5-(4-bromo-2-chlorophenyl)furan-2yl]-N-[(piperidin-4-yl)methyl]methanamine) was selected from the MMV Malaria Box for its dual activity against both asexual stages and gametocytes. In-depth structure-activity relationship studies and cytotoxicity evaluation led to the selection of 25 for further biological investigation. The potential transmission blocking activity of 25 versus P. falciparum was confirmed through the standard membrane feeding assay. Both 1 and 25 significantly prolonged atrioventricular conduction time in Langendorff-isolated rat hearts, and showed inhibitory activity of Ba2+ current through Ca(v)1.2 channels. An in silico target-fishing study suggested the enzyme phosphoethanolamine methyltransferase (PfPMT) as a potential target. However, compound activity against PfPMT did not track with the antiplasmodial activity, suggesting the latter activity relies on a different molecular target. Nevertheless, 25 showed interesting activity against PfPMT, which could be an important starting point for the identification of more potent inhibitors active against both sexual and asexual stages of the parasite. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.03.024

文献信息

• Antimalarial agents against both sexual and asexual parasites stages: structure-activity relationships and biological studies of the Malaria Box compound 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine (MMV019918) and analogues
  作者：Alessandra Vallone、Sarah D'Alessandro、Simone Brogi、Margherita Brindisi、Giulia Chemi、Gloria Alfano、Stefania Lamponi、Soon Goo Lee、Joseph M. Jez、Karin J.M. Koolen、Koen J. Dechering、Simona Saponara、Fabio Fusi、Beatrice Gorelli、Donatella Taramelli、Silvia Parapini、Reto Caldelari、Giuseppe Campiani、Sandra Gemma、Stefania Butini

  DOI：10.1016/j.ejmech.2018.03.024

  日期：2018.4

  Therapies addressing multiple stages of Plasmodium falciparum life cycle are highly desirable for implementing malaria elimination strategies. MMV019918 (1, 1-[5-(4-bromo-2-chlorophenyl)furan-2yl]-N-[(piperidin-4-yl)methyl]methanamine) was selected from the MMV Malaria Box for its dual activity against both asexual stages and gametocytes. In-depth structure-activity relationship studies and cytotoxicity evaluation led to the selection of 25 for further biological investigation. The potential transmission blocking activity of 25 versus P. falciparum was confirmed through the standard membrane feeding assay. Both 1 and 25 significantly prolonged atrioventricular conduction time in Langendorff-isolated rat hearts, and showed inhibitory activity of Ba2+ current through Ca(v)1.2 channels. An in silico target-fishing study suggested the enzyme phosphoethanolamine methyltransferase (PfPMT) as a potential target. However, compound activity against PfPMT did not track with the antiplasmodial activity, suggesting the latter activity relies on a different molecular target. Nevertheless, 25 showed interesting activity against PfPMT, which could be an important starting point for the identification of more potent inhibitors active against both sexual and asexual stages of the parasite. (C) 2018 Elsevier Masson SAS. All rights reserved.