N-(7-chloro-4-quinolyl)-N′-ferrocenyl-propane-1,3-diamine | 907587-79-5

• 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: N-(7-chloro-4-quinolyl)-N′-ferrocenyl-propane-1,3-diamine
• 英文别名: {3-[(7-chloroquinolin-4-yl)amino]propyl}(ferrocenylmethyl)amine；N1-(7-chloro-4-quinolyl)-N2-ferrocenyl 1,3-propanediamine；N1-(7-chloro-4-quinolyl)-N2-ferrocenyl-1,3-propanediamine；N'-(7-chloroquinolin-4-yl)-N-(cyclopenta-2,4-dien-1-ylmethyl)propane-1,3-diamine;cyclopenta-1,3-diene;iron(2+)
• CAS: 907587-79-5
• 化学式: C₂₃H₂₄ClFeN₃
• 分子量: 433.764
• InChiKey: SDYCMMSHVGXSQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  37
• 氢给体数：
  2
• 氢受体数：
  5

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-propane-1,3-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

• 1,2-Disubstituted ferrocenyl carbohydrate chloroquine conjugates as potential antimalarial agents
  作者：Christoph Herrmann、Paloma F. Salas、Brian O. Patrick、Carmen de Kock、Peter J. Smith、Michael J. Adam、Chris Orvig

  DOI：10.1039/c2dt12050j

  日期：——

  This work presents a new family of organometallic antimalarial compounds consisting of ferrocene bearing a chloroquine-derived moiety as well as a 1,2;3,5-diisopropylidene glucofuranose moiety at a cyclopentadienyl scaffold in a 1,2-substitution pattern. The synthetic route proceeds via a stereoselective functionalization of ferrocene carboxaldehyde to the 1,2-disubstituted conjugates. After complete

  这项工作提出了一个新的有机金属抗疟化合物家族，包括 二茂铁在环戊二烯基支架上以1，2-取代方式带有氯喹衍生的部分以及1,2; 3,5-二异亚丙基葡糖呋喃糖部分。合成途径是通过将二茂铁羧醛立体选择性官能化为1,2-二取代的共轭物而进行的。在对这些新的三功能结合物进行完全表征后，检查了它们在两种癌细胞系（MDA-MB-435S和Caco2）和一种非癌细胞系（MCF-10A）中的细胞毒性，表明可以观察到增加的细胞毒性与它们的碳水化合物取代的前体相比，氯喹二茂铁基共轭物具有更大的可比性。结合物在恶性疟原虫氯喹敏感菌株中的抗血浆活性（D10）和抗氯喹菌株（Dd2）被确定。单取代的缀合物13，14和15显示出降低的活性随二茂铁和喹啉部分之间的烷基链长度，双功能偶联物16，17，18示出恒定的活性，进行优于氯喹 在Dd2株中。
• 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.