N-(7-chloro-4-quinolyl)-N',N'-diethyl-1,5-diaminopentane

• 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',N'-diethyl-1,5-diaminopentane
• 英文别名: N-(7-chloroquinolin-4-yl)-N',N'-diethylpentane-1,5-diamine
• 化学式: C₁₈H₂₆ClN₃
• 分子量: 319.878
• InChiKey: KASRWENZOKSTKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  28.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  7-氯-4-羟基喹啉 在 sodium tetrahydroborate 、 三氯氧磷 作用下， 反应 23.0h， 生成 N-(7-chloro-4-quinolyl)-N',N'-diethyl-1,5-diaminopentane
  参考文献：
  名称：

  抗疟药：合成4-氨基喹啉类药物，可在疟疾寄生虫中规避耐药性†

  摘要：

  此处描述的策略已允许合成一系列4-氨基喹啉抗疟药。对先前合成方法的实质性改进包括用纯胺而不是苯酚进行亲核取代，区域选择性还原烷基化以将二氨基烷烃侧链上的末端伯胺（12a-20a）转化为二乙氨基，以及通过使用碱性氧化铝的柱色谱法进行纯化。用硼氘化钠（与硼氢化钠相比）进行区域选择性还原烷基化后获得的1 H nmr光谱表明，该还原烷基化是通过形成并随后原位还原相应的二酰胺而进行的。

  DOI：

  10.1002/jhet.5570340149

文献信息

• Antimalarial Quinolines and Methods of Use Thereof
  申请人：Wolf Christian

  公开号：US20110045100A1

  公开（公告）日：2011-02-24

  One aspect of the invention relates to substitute quinolines with antimalarial activity, and compositions and kits comprising at least one of them. Another aspect of the invention relates to methods for the treatment or prevention or both of malaria comprising administering to a subject a therapeutically effective amount of such a compound. Importantly, a number of the compounds show excellent potency against both chloroquine-sensitive and chloroquine-resistant strains.

  本发明的一个方面涉及具有抗疟活性的替代喹啉，以及包含至少其中之一的组合物和试剂盒。另一个方面涉及用这种化合物向受试者施用治疗有效量的方法，以治疗或预防疟疾。重要的是，其中一些化合物对氯喹敏感和氯喹耐药菌株都表现出极高的效力。
• 4-<i>N</i>-, 4-<i>S</i>-, and 4-<i>O</i>-Chloroquine Analogues: Influence of Side Chain Length and Quinolyl Nitrogen p<i>K</i>_a on Activity vs Chloroquine Resistant Malaria
  作者：Jayakumar K. Natarajan、John N. Alumasa、Kimberly Yearick、Kekeli A. Ekoue-Kovi、Leah B. Casabianca、Angel C. de Dios、Christian Wolf、Paul D. Roepe

  DOI：10.1021/jm701478a

  日期：2008.6.1

  Using predictions from heme-quinoline antimalarial complex structures, previous modifications of chloroquine (CQ), and hypotheses for chloroquine resistance (CQR), we synthesize and assay CQ analogues that test structure-function principles. We vary side chain length for both monoethyl and diethyl 4-N CQ derivatives. We alter the pK(a) of the quinolyl N by introducing alkylthio or alkoxy substituents into the 4 position and vary side chain length for these analogues. We introduce an additional titratable amino group to the side chain of 4-O analogues with promising CQR strain selectivity and increase activity while retaining selectivity. We solve atomic resolution structures for complexes formed between representative 4-N, 4-S, and 4-O derivatives vs mu-oxo dimeric heme, measure binding constants for monomeric vs dimeric heme, and quantify hemozoin (Hz) formation inhibition in vitro. The data provide additional insight for the design of CQ analogues with improved activity vs CQR malaria.
• [EN] ANTIMALARIAL QUINOLINES AND METHODS OF USE THEREOF<br/>[FR] QUINOLÉINES ANTIPALUDIQUES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV GEORGETOWN

  公开号：WO2009148659A2

  公开（公告）日：2009-12-10

  One aspect of the invention relates to substitute quinolines with antimalarial activity, and compositions and kits comprising at least one of them. Another aspect of the invention relates to methods for the treatment or prevention or both of malaria comprising administering to a subject a therapeutically effective amount of such a compound. Importantly, a number of the compounds show excellent potency against both chloroquine-sensitive and chloroquine-resistant strains.
• Antimalarials: Synthesis of 4-aminoquinolines that circumvent drug resistance in malaria parasites
  作者：Dibyendu De、Larry D. Byers、Donald J. Krogstad

  DOI：10.1002/jhet.5570340149

  日期：1997.1

  substitution with neat amine rather than in phenol, regioselective reductive alkylation to convert the terminal primary amine (12a–20a) on the diaminoalkane side chain to a diethylamino group, and purification by column chromatography with basic alumina. The 1H nmr spectra obtained after regioselective reductive alkylation with sodium borodeuteride (in comparison with sodium borohydride) demonstrated that

  此处描述的策略已允许合成一系列4-氨基喹啉抗疟药。对先前合成方法的实质性改进包括用纯胺而不是苯酚进行亲核取代，区域选择性还原烷基化以将二氨基烷烃侧链上的末端伯胺（12a-20a）转化为二乙氨基，以及通过使用碱性氧化铝的柱色谱法进行纯化。用硼氘化钠（与硼氢化钠相比）进行区域选择性还原烷基化后获得的1 H nmr光谱表明，该还原烷基化是通过形成并随后原位还原相应的二酰胺而进行的。