6-(4-methoxyphenyl)-7H-indeno[2,1-c][1,5]naphthyridine

• 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: 6-(4-methoxyphenyl)-7H-indeno[2,1-c][1,5]naphthyridine
• 化学式: C₂₂H₁₆N₂O
• 分子量: 324.382
• InChiKey: GYLXPNFTLQHCQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-氨基吡啶 在 三氟化硼乙醚 作用下， 以 氯仿 为溶剂， 反应 32.0h， 生成 6-(4-methoxyphenyl)-7H-indeno[2,1-c][1,5]naphthyridine
  参考文献：
  名称：

  Antileishmanial effect of new indeno-1,5-naphthyridines, selective inhibitors of Leishmania infantum type IB DNA topoisomerase

  摘要：

  Visceral leishmaniasis is a neglected disease of poor and developing countries. The current therapeutic approach is based on pentavalent antimonial (Sb-V) drugs and amphotericin B, both nephrotoxic and parenterally administered drugs. Therefore, there is a real need of new antileishmanial drugs. Eukaryotic type I DNA topoisomerases (TopIB) have been identified as druggable targets against leishmaniasis. These enzymes are involved in solving topological problems generated during replication, transcription and recombination of DNA. Leishmanial TopIB is a unique heterodimeric protein structurally different than that found in the mammalian host, thus making it an interesting target for drug discovery. Tetrahydro indeno-1,5-naphthyridines 5 and indeno[1,5]naphthyridines 6 were synthesized. The inhibition of Leishmania and human TopIB of these polycyclic heterocycles were studied and their antileishmanial activity on promastigotes and amastigote-infected splenocytes of Leishmania infantum were evaluated. In this regard, it is noteworthy that some of the prepared heterocycles, as compounds 6b, 6i and 5 h, showed selective inhibition of LtopIB while no inhibition of hToplB was observed at evaluated conditions. In addition, the cytotoxic effects of newly synthesized compounds were assessed on host murine splenocytes in order to calculate the corresponding selective indexes (SI). Tetrahydro indeno-1,5-naphthyridines 5e and 5h showed good antileishmanial activity (IC50 values of 0.67 +/- 0.06 and 0.54 +/- 0.17 mu M) with similar activity than the standard drug amphotericin B (0.32 +/- 0.05 mu M) and even tetrahydro indeno-1,5-naphthyridine 5h showed higher (SI) towards L. Infantum amastigotes. Likewise, in the family of indeno-[1,5]-naphthyridines 6, compound 6b showed good antileishmanial activity (IC50 value 0.74 +/- 0.08 mu M) and higher selective index (SI) towards L Infantum amastigotes than amphotericin B. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.09.017

文献信息

• Antileishmanial effect of new indeno-1,5-naphthyridines, selective inhibitors of Leishmania infantum type IB DNA topoisomerase
  作者：Ana Tejería、Yolanda Pérez-Pertejo、Rosa M. Reguera、Rafael Balaña-Fouce、Concepción Alonso、María Fuertes、María González、Gloria Rubiales、Francisco Palacios

  DOI：10.1016/j.ejmech.2016.09.017

  日期：2016.11

  Visceral leishmaniasis is a neglected disease of poor and developing countries. The current therapeutic approach is based on pentavalent antimonial (Sb-V) drugs and amphotericin B, both nephrotoxic and parenterally administered drugs. Therefore, there is a real need of new antileishmanial drugs. Eukaryotic type I DNA topoisomerases (TopIB) have been identified as druggable targets against leishmaniasis. These enzymes are involved in solving topological problems generated during replication, transcription and recombination of DNA. Leishmanial TopIB is a unique heterodimeric protein structurally different than that found in the mammalian host, thus making it an interesting target for drug discovery. Tetrahydro indeno-1,5-naphthyridines 5 and indeno[1,5]naphthyridines 6 were synthesized. The inhibition of Leishmania and human TopIB of these polycyclic heterocycles were studied and their antileishmanial activity on promastigotes and amastigote-infected splenocytes of Leishmania infantum were evaluated. In this regard, it is noteworthy that some of the prepared heterocycles, as compounds 6b, 6i and 5 h, showed selective inhibition of LtopIB while no inhibition of hToplB was observed at evaluated conditions. In addition, the cytotoxic effects of newly synthesized compounds were assessed on host murine splenocytes in order to calculate the corresponding selective indexes (SI). Tetrahydro indeno-1,5-naphthyridines 5e and 5h showed good antileishmanial activity (IC50 values of 0.67 +/- 0.06 and 0.54 +/- 0.17 mu M) with similar activity than the standard drug amphotericin B (0.32 +/- 0.05 mu M) and even tetrahydro indeno-1,5-naphthyridine 5h showed higher (SI) towards L. Infantum amastigotes. Likewise, in the family of indeno-[1,5]-naphthyridines 6, compound 6b showed good antileishmanial activity (IC50 value 0.74 +/- 0.08 mu M) and higher selective index (SI) towards L Infantum amastigotes than amphotericin B. (C) 2016 Elsevier Masson SAS. All rights reserved.