N⁶-(4-methoxybenzyl)quinazoline-2,4,6-triamine | 13919-69-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N⁶-(4-methoxybenzyl)quinazoline-2,4,6-triamine
• 英文别名: N⁶-(4-methoxy-benzyl)-quinazoline-2,4,6-triamine；6-N-[(4-methoxyphenyl)methyl]quinazoline-2,4,6-triamine
• CAS: 13919-69-2
• 化学式: C₁₆H₁₇N₅O
• 分子量: 295.344
• InChiKey: RQSBJSIIKPEFOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  对三氟甲氧基苯甲醛 、 N⁶-(4-methoxybenzyl)quinazoline-2,4,6-triamine 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 乙腈 为溶剂， 反应 168.0h， 以63%的产率得到N⁶-(4-methoxybenzyl)-N⁶-(4-trifluoromethoxybenzyl)quinazoline-2,4,6-triamine
  参考文献：
  名称：

  Design, synthesis and biological evaluation of quinazoline derivatives as anti-trypanosomatid and anti-plasmodial agents

  摘要：

  In this paper, the design, synthesis and biological evaluation of a set of quinazoline-2,4,6-triamine derivatives (1-9) as trypanocidal, antileishmanial and antiplasmodial agents are explained. The compounds were rationalized basing on docking studies of the dihydrofolate reductase (DHFR from Trypanosoma cruzi, Leishmania major and Plasmodium vivax) and pteridin reductase (PTR from T. cruzi and L major) structures. All compounds were in vitro screened against both bloodstream trypomastigotes of T cruzi (NINOA and INC-5 strains) and prornatigotes of Leishmania mexicana (MHOM/BZ/61/M379 strain), and also for cytotoxicity using Vero cell line. Against T. cruzi, three compounds (5, 6 and 8) were the most effective showing a better activity profile than nifurtimox and benznidazole (reference drugs). Against L. mexicana, four compounds (5, 6, 8, and 9) exhibited the highest activity, even than glucantime (reference drug). In the cytotoxicity assay, protozoa were more susceptible than Vero cells. In vivo Plasmodium berghei assay (ANKA strain), the compounds 1, 5, 6 and 8 showed a more comparable activity than chloroquine and pyrimethamine (reference drugs) when they were administrated by the oral route. The antiprotozoal activity of these substances, endowed with redox properties, represented a good starting point for a medicinal chemistry program aiming for chemotherapy of Chagas' disease, leishmaniosis and malaria. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.04.028
• 作为产物：
  描述：

  2-氰基-4-硝基苯胺 在 sodium hydroxide 作用下， 以 甲醇 、 乙醇 为溶剂， 100.0 ℃ 、413.7 kPa 条件下， 反应 127.33h， 生成 N⁶-(4-methoxybenzyl)quinazoline-2,4,6-triamine
  参考文献：
  名称：

  Antileishmanial activity of quinazoline derivatives: Synthesis, docking screens, molecular dynamic simulations and electrochemical studies

  摘要：

  A series of quinazoline-2,4,6-triamine were synthesized and evaluated in vitro against Leishmania mexicana. Among them, N-6-(ferrocenmethyl)quinazolin-2,4,6-triamine (II2) showed activity on promastigotes and intracellular amastigotes, as well as low cytotoxicity in mammalian cells. Docking and electrochemical studies showed the importance of both the ferrocene and the heterocyclic nucleus to the observed activity. 142 is readily oxidized electrochemically, indicating that the mechanism of action probably involves redox reactions. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.051

文献信息

• Antileishmanial activity of quinazoline derivatives: Synthesis, docking screens, molecular dynamic simulations and electrochemical studies
  作者：Cesar Mendoza-Martínez、Norma Galindo-Sevilla、José Correa-Basurto、Victor Manuel Ugalde-Saldivar、Rosa Georgina Rodríguez-Delgado、Jessica Hernández-Pineda、Cecilia Padierna-Mota、Marcos Flores-Alamo、Francisco Hernández-Luis

  DOI：10.1016/j.ejmech.2014.12.051

  日期：2015.3

  A series of quinazoline-2,4,6-triamine were synthesized and evaluated in vitro against Leishmania mexicana. Among them, N-6-(ferrocenmethyl)quinazolin-2,4,6-triamine (II2) showed activity on promastigotes and intracellular amastigotes, as well as low cytotoxicity in mammalian cells. Docking and electrochemical studies showed the importance of both the ferrocene and the heterocyclic nucleus to the observed activity. 142 is readily oxidized electrochemically, indicating that the mechanism of action probably involves redox reactions. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Design, synthesis and biological evaluation of quinazoline derivatives as anti-trypanosomatid and anti-plasmodial agents
  作者：César Mendoza-Martínez、José Correa-Basurto、Rocío Nieto-Meneses、Adrián Márquez-Navarro、Rocío Aguilar-Suárez、Miriam Dinora Montero-Cortes、Benjamín Nogueda-Torres、Erick Suárez-Contreras、Norma Galindo-Sevilla、Ángela Rojas-Rojas、Alejandro Rodriguez-Lezama、Francisco Hernández-Luis

  DOI：10.1016/j.ejmech.2015.04.028

  日期：2015.5

  In this paper, the design, synthesis and biological evaluation of a set of quinazoline-2,4,6-triamine derivatives (1-9) as trypanocidal, antileishmanial and antiplasmodial agents are explained. The compounds were rationalized basing on docking studies of the dihydrofolate reductase (DHFR from Trypanosoma cruzi, Leishmania major and Plasmodium vivax) and pteridin reductase (PTR from T. cruzi and L major) structures. All compounds were in vitro screened against both bloodstream trypomastigotes of T cruzi (NINOA and INC-5 strains) and prornatigotes of Leishmania mexicana (MHOM/BZ/61/M379 strain), and also for cytotoxicity using Vero cell line. Against T. cruzi, three compounds (5, 6 and 8) were the most effective showing a better activity profile than nifurtimox and benznidazole (reference drugs). Against L. mexicana, four compounds (5, 6, 8, and 9) exhibited the highest activity, even than glucantime (reference drug). In the cytotoxicity assay, protozoa were more susceptible than Vero cells. In vivo Plasmodium berghei assay (ANKA strain), the compounds 1, 5, 6 and 8 showed a more comparable activity than chloroquine and pyrimethamine (reference drugs) when they were administrated by the oral route. The antiprotozoal activity of these substances, endowed with redox properties, represented a good starting point for a medicinal chemistry program aiming for chemotherapy of Chagas' disease, leishmaniosis and malaria. (C) 2015 Elsevier Masson SAS. All rights reserved.