tert-butyl 1-(3-chlorophenyl)-2,4-diamino-1,3,5,9-tetraazaspiro[5.5]undeca-2,4-diene-9-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: tert-butyl 1-(3-chlorophenyl)-2,4-diamino-1,3,5,9-tetraazaspiro[5.5]undeca-2,4-diene-9-carboxylate
• 英文别名: Tert-butyl 2,4-diamino-5-(3-chlorophenyl)-1,3,5,9-tetrazaspiro[5.5]undeca-1,3-diene-9-carboxylate；tert-butyl 2,4-diamino-5-(3-chlorophenyl)-1,3,5,9-tetrazaspiro[5.5]undeca-1,3-diene-9-carboxylate
• 化学式: C₁₈H₂₅ClN₆O₂
• 分子量: 392.888
• InChiKey: FKLLPPRRMCOWRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 1-(3-chlorophenyl)-2,4-diamino-1,3,5,9-tetraazaspiro[5.5]undeca-2,4-diene-9-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以89%的产率得到1-(3-chlorophenyl)-2,4-diamino-1,3,5,9-tetraazaspiro[5.5]undeca-2,4-diene
  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
• 作为产物：
  描述：

  N-叔丁氧羰基-4-哌啶酮 、 二聚氰胺 、 3-氯苯胺 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 17.0h， 以37%的产率得到tert-butyl 1-(3-chlorophenyl)-2,4-diamino-1,3,5,9-tetraazaspiro[5.5]undeca-2,4-diene-9-carboxylate
  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