N-(7-chloro-4-quinolyl)-N′-ferrocenyl-butane-1,4-diamine | 907587-81-9

• 英文名称: N-(7-chloro-4-quinolyl)-N′-ferrocenyl-butane-1,4-diamine
• 英文别名: {4-[(7-chloroquinolin-4-yl)amino]butyl}(ferrocenylmethyl)amine
• CAS: 907587-81-9
• 化学式: C₂₄H₂₆ClFeN₃
• 分子量: 447.791
• InChiKey: ZDUULQQEBYIWEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
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• 重原子数：
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• 可旋转键数：
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• 环数：
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• sp3杂化的碳原子比例：
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• 拓扑面积：
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• 氢给体数：
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• 氢受体数：
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反应信息

• 作为产物：
  描述：

  在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 N-(7-chloro-4-quinolyl)-N′-ferrocenyl-butane-1,4-diamine
  参考文献：
  名称：

  Synthesis, in vitro antiplasmodial and antiproliferative activities of a series of quinoline–ferrocene hybrids

  摘要：

  Series of quinoline-ferrocene hybrids containing various linkers were synthesized and evaluated for antimalarial and anticancer activities as well as cytotoxicity. The hybrids with rigid linkers were found to be inactive, while those with flexible spacers showed activity against both the D10 and Dd2 strains of Plasmodium falciparum, and demonstrated a good selectivity towards these parasitic cells in comparison with emetine. The hybrid 16, featuring 3-aminopropyl methylamine linker, was the most antimalarial active compound, exhibiting a significantly better potency than chloroquine against the Dd2 strain (IC50 = 0.008 vs. 0.148 mu M; 19-fold), and was also found to be significantly more active than the equimolar chloroquine-ferrocene combination (IC50 = 3.7 vs. 41 ng/ml, tenfold) against the Dd2 strain. Anticancer activity screening showed that all the antimalarial active hybrids also exhibited potent cytostatic (GI(50) = 0.6-3.3 mu M) and had good cytotoxic effects (LC50 = 6-8 mu M) against all three cancer cell lines. The hybrid 11 possessing 1,4-butanediamine linker was distinctively the most antiproliferative of all. It was found to be more cytostatic (GI(50): 0.7 vs. 5.9 mu M, eightfold) and (LC50: 6.4 vs. 92.6 mu M, 14-fold) more cytotoxic than etoposide against the TK10 (renal) cell line.

  DOI：

  10.1007/s00044-013-0748-4

文献信息

• Structural Characteristics of Chloroquine-Bridged Ferrocenophane Analogues of Ferroquine May Obviate Malaria Drug-Resistance Mechanisms
  作者：Paloma F. Salas、Christoph Herrmann、Jacqueline F. Cawthray、Corinna Nimphius、Alexander Kenkel、Jessie Chen、Carmen de Kock、Peter J. Smith、Brian O. Patrick、Michael J. Adam、Chris Orvig

  DOI：10.1021/jm301422h

  日期：2013.2.28

  Five compounds displaying an unprecedented binding mode of chloroquine to ferrocene through the bridging of the cyclopentadienyl rings were studied alongside their monosubstituted ferrocene analogues and organic fragments. The antiplasmodial activity was evaluated against strains of the malaria parasite (Plasmodium falciparum). While the chloroquine-bridged ferrocenyl derivatives were less active than their five monosubstituted ferrocenyl analogues, they retained activity in the drug-resistant strains. The biological and physical properties were correlated to antiplasmodial activity. Intramolecular hydrogen bonding was associated with increased antiplasmodial action, but it is not the determining factor. Instead, balance between lipophilicity and hydrophilicity had a greater influence. It was found that calculated partition coefficient (log P) values of 4.5-5.0 and topological polar surfaces area (tPSA) values of similar to 26.0 angstrom(2) give the best balance. The particular conformation, compact size, and lipophilicity/hydrophilicity balance observed in the bridged compounds provide them with the structural characteristics needed to escape the mechanisms responsible for resistance.