3,9-dimethyl-N,N'-bis(2-pyrrolidin-1-ylethyl)quino[8,7-h]quinoline-1,7-diamine tetrahydrochloride

• 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: 3,9-dimethyl-N,N'-bis(2-pyrrolidin-1-ylethyl)quino[8,7-h]quinoline-1,7-diamine tetrahydrochloride
• 英文别名: 3,9-dimethyl-1-N,7-N-bis(2-pyrrolidin-1-ylethyl)quinolino[8,7-h]quinoline-1,7-diamine;hydrochloride
• 化学式: C₃₀H₃₈N₆*4ClH
• 分子量: 628.516
• InChiKey: AFZZLRINBBQNKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.99
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  56.3
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1,5-萘二胺 在 甲烷磺酸 、 四磷十氧化物 、 对甲苯磺酸 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 125.0h， 生成 3,9-dimethyl-N,N'-bis(2-pyrrolidin-1-ylethyl)quino[8,7-h]quinoline-1,7-diamine tetrahydrochloride
  参考文献：
  名称：

  A Chemotype That Inhibits Three Unrelated Pathogenic Targets: The Botulinum Neurotoxin Serotype A Light Chain, P. falciparum Malaria, and the Ebola Filovirus

  摘要：

  A 1,7-bis(alkylamino)diazachrysene-based small molecule was previously identified as an inhibitor of the botulinum neurotoxin serotype A light chain metalloprotease. Subsequently, a variety of derivatives of this chemotype were synthesized to develop structure activity relationships, and all are inhibitors of the BoNT/A LC. Three-dimensional analyses indicated that half of the originally discovered 1,7-DAAC structure superimposed well with 4-amino-7-chloroquinolinebased antimalarial agents. This observation led to the discovery that several of the 1,7-DAAC derivatives are potent in vitro inhibitors of Plasmodium falciparum and, in general, are more efficacious against CQ-resistant strains than against CQ-susceptible strains. In addition, by inhibiting beta-hematin formation, the most efficacious 1,7-DAAC-based antimalarials employ a mechanism of action analogous to that of 4,7-ACQ-based antimalarials and are well tolerated by normal cells. One candidate was also effective when administered orally in a rodent-based malaria model. Finally, the 1,7-DAAC-based derivatives were examined for Ebola filovirus inhibition in an assay employing Vero76 cells, and three provided promising antiviral activities and acceptably low toxicities.

  DOI：

  10.1021/jm100938u

文献信息

• A Chemotype That Inhibits Three Unrelated Pathogenic Targets: The Botulinum Neurotoxin Serotype A Light Chain, <i>P. falciparum</i> Malaria, and the Ebola Filovirus
  作者：Igor Opsenica、James C. Burnett、Rick Gussio、Dejan Opsenica、Nina Todorović、Charlotte A. Lanteri、Richard J. Sciotti、Montip Gettayacamin、Nicoletta Basilico、Donatella Taramelli、Jonathan E. Nuss、Laura Wanner、Rekha G. Panchal、Bogdan A. Šolaja、Sina Bavari

  DOI：10.1021/jm100938u

  日期：2011.3.10

  A 1,7-bis(alkylamino)diazachrysene-based small molecule was previously identified as an inhibitor of the botulinum neurotoxin serotype A light chain metalloprotease. Subsequently, a variety of derivatives of this chemotype were synthesized to develop structure activity relationships, and all are inhibitors of the BoNT/A LC. Three-dimensional analyses indicated that half of the originally discovered 1,7-DAAC structure superimposed well with 4-amino-7-chloroquinolinebased antimalarial agents. This observation led to the discovery that several of the 1,7-DAAC derivatives are potent in vitro inhibitors of Plasmodium falciparum and, in general, are more efficacious against CQ-resistant strains than against CQ-susceptible strains. In addition, by inhibiting beta-hematin formation, the most efficacious 1,7-DAAC-based antimalarials employ a mechanism of action analogous to that of 4,7-ACQ-based antimalarials and are well tolerated by normal cells. One candidate was also effective when administered orally in a rodent-based malaria model. Finally, the 1,7-DAAC-based derivatives were examined for Ebola filovirus inhibition in an assay employing Vero76 cells, and three provided promising antiviral activities and acceptably low toxicities.