6-methoxy-8-nitro-5-phenyl-quinoline | 855760-31-5

• 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: 6-methoxy-8-nitro-5-phenyl-quinoline
• 英文别名: 6-Methoxy-8-nitro-5-phenyl-chinolin
• CAS: 855760-31-5
• 化学式: C₁₆H₁₂N₂O₃
• 分子量: 280.283
• InChiKey: UTZVFAMJGXJSJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.82
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  65.26
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  6-methoxy-8-nitro-5-phenyl-quinoline 在 盐酸 、 tin 、 一水合肼 、 三乙胺 、 tin(ll) chloride 作用下， 以 乙醇 、 水 为溶剂， 反应 27.0h， 生成
  参考文献：
  名称：

  Endoperoxide-8-aminoquinoline hybrids as dual-stage antimalarial agents with enhanced metabolic stability

  摘要：

  Hybrid compounds may play a critical role in the context of the malaria eradication agenda, which will benefit from therapeutic tools active against the symptomatic erythrocytic stage of Plasmodium infection, and also capable of eliminating liver stage parasites, To address the need for efficient multistage antiplasmodial compounds, a small library of 1,2,4,5-tetraoxane-8-aminoquinoline hybrids, with the metabolically labile C-5 position of the 8-aminoquinoline moiety blocked with aryl groups, was synthesized and screened for antiplasmodial activity and metabolic stability. The hybrid compounds inhibited development of intra-erythrocytic forms of the multidrug-resistant Plasmodium falciparum W2 strain, with EC50 values in the nM range, and with low cytotoxicity against mammalian cells. The compounds also inhibited the development of P. berghei liver stage parasites, with the most potent compounds displaying EC50 values in the low mu M range. SAR analysis revealed that unbranched linkers between the endoperoxide and 8-aminoquinoline pharmacophores are most beneficial for dual antiplasmodial activity. Importantly, hybrids were significantly more potent than a 1:1 mixture of 8-aminoquinoline-tetraoxane, highlighting the superiority of the hybrid approach over the combination therapy. Furthermore, aryl substituents at C-5 of the 8-aminoquinoline moiety improve the compounds' metabolic stability when compared with their primaquine (i.e. C-5 unsubstituted) counterparts. Overall, this study reveals that blocking the quinoline C-5 position does not result in loss of dual-stage antimalarial activity, and that tetraoxane-8-aminoquinoline hybrids are an attractive approach to achieve elimination of exo- and intraerythrocytic parasites, thus with the potential to be used in malaria eradication campaigns. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.02.048
• 作为产物：
  描述：

  N-Acetyl-2-methoxy-5-aminobiphenyl 在 arsenic(V) oxide 、 硫酸 、 水 、 硝酸 、 溶剂黄146 、 甘油 作用下， 生成 6-methoxy-8-nitro-5-phenyl-quinoline
  参考文献：
  名称：

  8-（3'二乙基氨基丙基氨基）-6-甲氧基-5-苯基-喹啉的合成。

  摘要：

  DOI：

  10.1021/ja01212a047