8-benzyl-2,4-diamino-1-phenyl-1,3,5,8-tetraazaspiro[5.5]undeca-2,4-diene hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 8-benzyl-2,4-diamino-1-phenyl-1,3,5,8-tetraazaspiro[5.5]undeca-2,4-diene hydrochloride
• 英文别名: 8-Benzyl-5-phenyl-1,3,5,8-tetrazaspiro[5.5]undeca-1,3-diene-2,4-diamine;hydrochloride；8-benzyl-5-phenyl-1,3,5,8-tetrazaspiro[5.5]undeca-1,3-diene-2,4-diamine;hydrochloride
• 化学式: C₂₀H₂₄N₆*ClH
• 分子量: 384.912
• InChiKey: YQAGRYCOVVPOBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.55
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  83.2
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-苄基-3-哌啶酮盐酸盐 、 苯胺 、 二聚氰胺 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 7.0h， 以53%的产率得到8-benzyl-2,4-diamino-1-phenyl-1,3,5,8-tetraazaspiro[5.5]undeca-2,4-diene hydrochloride
  参考文献：
  名称：

  Synthesis, biological evaluation and molecular modeling of novel azaspiro dihydrotriazines as influenza virus inhibitors targeting the host factor dihydrofolate reductase (DHFR)

  摘要：

  Recently we identified cycloguanil-like dihydrotriazine derivatives, which provided host-factor directed antiviral activity against influenza viruses and respiratory syncytial virus (RSV), by targeting the human dihydrofolate reductase (hDHFR) enzyme. In this context we deemed interesting to further investigate the structure activity relationship (SAR) of our first series of cycloguanil-like dihydrotriazines, designing two novel azaspiro dihydrotriazine scaffolds. The present study allowed the exploration of the potential chemical space, around these new scaffolds, that are well tolerated for maintaining the antiviral effect by means of interaction with the hDHFR enzyme. The new derivatives confirmed their inhibitory profile against influenza viruses, especially type B. In particular, the two best compounds shared potent antiviral activity (4: EC50 = 0.29 mu M; 6: EC50 = 0.19 mu M), which was comparable to that of zanamivir (EC50 = 0.14 mu M), and better than that of ribavirin (EC50 = 3.2 mu M). In addition, these two compounds proved to be also effective against RSV (4: EC50 = 0.40 mu M, SI > 250; 6: EC50 = 1.8 mu M, SI > 56), surpassing the potency and selectivity index (SI) of ribavirin (EC50 = 5.8 mu M, SI >43). By a perspective of these results, the above adequately substituted azaspiro dihydrotriazines may represent valuable hit compounds worthy of further structural optimization to develop improved host DHFR-directed antiviral agents. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.05.059

文献信息

• Synthesis, biological evaluation and molecular modeling of novel azaspiro dihydrotriazines as influenza virus inhibitors targeting the host factor dihydrofolate reductase (DHFR)
  作者：Valeria Francesconi、Luca Giovannini、Matteo Santucci、Elena Cichero、Maria Paola Costi、Lieve Naesens、Fabrizio Giordanetto、Michele Tonelli

  DOI：10.1016/j.ejmech.2018.05.059

  日期：2018.7

  Recently we identified cycloguanil-like dihydrotriazine derivatives, which provided host-factor directed antiviral activity against influenza viruses and respiratory syncytial virus (RSV), by targeting the human dihydrofolate reductase (hDHFR) enzyme. In this context we deemed interesting to further investigate the structure activity relationship (SAR) of our first series of cycloguanil-like dihydrotriazines, designing two novel azaspiro dihydrotriazine scaffolds. The present study allowed the exploration of the potential chemical space, around these new scaffolds, that are well tolerated for maintaining the antiviral effect by means of interaction with the hDHFR enzyme. The new derivatives confirmed their inhibitory profile against influenza viruses, especially type B. In particular, the two best compounds shared potent antiviral activity (4: EC50 = 0.29 mu M; 6: EC50 = 0.19 mu M), which was comparable to that of zanamivir (EC50 = 0.14 mu M), and better than that of ribavirin (EC50 = 3.2 mu M). In addition, these two compounds proved to be also effective against RSV (4: EC50 = 0.40 mu M, SI > 250; 6: EC50 = 1.8 mu M, SI > 56), surpassing the potency and selectivity index (SI) of ribavirin (EC50 = 5.8 mu M, SI >43). By a perspective of these results, the above adequately substituted azaspiro dihydrotriazines may represent valuable hit compounds worthy of further structural optimization to develop improved host DHFR-directed antiviral agents. (C) 2018 Elsevier Masson SAS. All rights reserved.