N¹,N²-bis(7-chloroquinolin-4-yl)dodecane-1,12-diamine | 140926-86-9

• 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: N¹,N²-bis(7-chloroquinolin-4-yl)dodecane-1,12-diamine
• 英文别名: N,N'-bis(7-chloroquinolin-4-yl)dodecane-1,12-diamine
• CAS: 140926-86-9
• 化学式: C₃₀H₃₆Cl₂N₄
• 分子量: 523.549
• InChiKey: FGEISUJUAGRHKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.1
• 重原子数：
  36
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  49.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4,7-二氯喹啉 、 1,12-二氨基十二烷 在 sodium iodide 作用下， 以 苯酚 为溶剂， 生成 N¹,N²-bis(7-chloroquinolin-4-yl)dodecane-1,12-diamine
  参考文献：
  名称：

  Structure–Activity Relationship Studies of 9-Alkylamino-1,2,3,4-tetrahydroacridines against Leishmania (Leishmania) infantum Promastigotes

  摘要：

  利什曼病是现代最被忽视的疾病之一，主要影响热带、亚热带和地中海盆地的发展中国家人群，约有3.5亿人可能患上该病。由于预防和治疗措施的失败，人类利什曼病的发病率在过去几十年中增加了，目前没有疫苗和化疗，这是一个问题。吖啶衍生物是一类氮杂环化合物，与众多生物活性相关，尤其是它们的抗利什曼病潜力。本研究基于对寄生虫酶S-腺苷甲硫氨酸脱羧酶（AdoMet DC）的计算研究，发现多种1,2,3,4-四氢-吖啶可能是潜在的抑制剂，表明该支架是新型抗利什曼病药物的有前途的构建块。因此，合成了多种1,2,3,4-四氢吖啶衍生物，评估了它们对利什曼原虫（利什曼原虫）幼虫的活性，并根据所得结果开展了结构-活性关系（SAR）研究。尽管大多数评估的1,2,3,4-四氢吖啶衍生物表现出高毒性，但本研究收集的结构信息使其可以与另一个支架（喹啉）结合使用，导致获得N1，N12-双（7-氯喹啉-4-基）十二烷基-1,12-二胺（12）作为有前途的新型抗利什曼病药物（IC50 = 0.60±0.11μM，EC50 = 11.69±3.96μM和TI = 19.48）。

  DOI：

  10.3390/pharmaceutics15020669

文献信息

• Bisquinolines. 1. N,N-bis(7-chloroquinolin-4-yl)alkanediamines with potential against chloroquine-resistant malaria
  作者：Jonathan L. Vennerstrom、William Y. Ellis、Arba L. Ager、Steven L. Andersen、Lucia Gerena、Wilbur K. Milhous

  DOI：10.1021/jm00089a025

  日期：1992.5

  On the basis of observations that several bisquinolines such as piperaquine possess notable activity against chloroquine-resistant malaria, 13 N,N-bis-(7-chloroquinolin-4-yl)alkanediamines were synthesized and screened against Plasmodium falciparum in vitro and Plasmodium berghei in vivo. Twelve of the thirteen bisquinolines had a significantly lower resistance index than did chloroquine; the resistance index was apparently unrelated to either in vitro or in vivo activity. Except for two compounds, there was a reasonable correlation between in vitro and in vivo activities. Seven of the thirteen bisquinolines had IC50's of less than 6 nM against both chloroquine-sensitive (D-6) and -resistant (W-2) clones of P. falciparum and were curative against P. berghei at doses of 640 mg/kg. In contrast to chloroquine, these bisquinolines did not show any toxic deaths at curative dose levels. Four bisquinolines, however, caused skin lesions at the site of injection. Maximum activity was seen in bisquinolines with a connecting bridge of two carbon atoms where decreased conformational mobility seemed to increase activity. Bisquinoline 3 ((+/-)-trans-N1,N2-bis(7-chloroquinolin-4-yl)cyclohexane-1,2-diamine was not only the most potent bisquinoline in vitro, but was clearly unique in its in vivo activity-80% and 100% cure rates were achieved at doses of 160 and 320 mg/kg, respectively. In summary, these preliminary results support the premise that bisquinolines may be useful agents against chloroquine-resistant malaria.