N-(7-chloro-4-quinolyl)-N'-ethyl-1,4-diaminobutane | 1033132-01-2

• 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'-ethyl-1,4-diaminobutane
• 英文别名: N'-(7-chloroquinolin-4-yl)-N-ethylbutane-1,4-diamine
• CAS: 1033132-01-2
• 化学式: C₁₅H₂₀ClN₃
• 分子量: 277.797
• InChiKey: AFQBCKMNPWLDPU-UHFFFAOYSA-N

物化性质

• 沸点：
  446.4±40.0 °C(Predicted)
• 密度：
  1.159±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  37
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(7-chloro-4-quinolyl)-N'-ethyl-1,4-diaminobutane 、 2-(5-dimethylaminonaphthalene-1-sulfonamido)ethyl methanesulfonate 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以75%的产率得到N-[2-{N'-4-(7-chloro-4-quinolyl)aminobutyl-N''-ethyl}aminoethyl]-5-dimethylaminonaphthalene-1-sulfonamide
  参考文献：
  名称：

  新型 4-氨基-7-氯喹啉酰胺、磺胺、尿素和硫脲的合成和抗疟活性

  摘要：

  我们报告了 50 多种 7-氯-4-氨基喹啉衍生的磺酰胺3 – 8和11 – 26、尿素19 – 22、硫脲23 – 26和酰胺27 – 54的合成和体外抗疟活性。许多为本研究制备的 CQ 类似物显示出亚微摩尔级抗疟活性，而 HB3（对氯喹敏感）和 Dd2（恶性疟原虫的氯喹抗性菌株）) 和低电阻指数在大多数情况下获得。侧链长度的系统变化和氟化脂肪族和芳香族末端的引入揭示了克服 CQ 抗性的有希望的线索。特别是，磺酰胺3具有短侧链和末端丹磺酰部分，结合了高抗疟原虫效力和低抗性指数，对 HB3 和 Dd2 寄生虫的IC 50 s 分别为 17.5 和 22.7 nM。

  DOI：

  10.1016/j.bmc.2008.11.009
• 作为产物：
  描述：

  溴乙烷 、 4-(4-氨基丁基)氨基-7-氯喹啉 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 以20%的产率得到N⁴-(7-chloro-4-quinolinyl)-N¹,N¹-diethyl-1,4-butanediamine
  参考文献：
  名称：

  4-N-, 4-S-, and 4-O-Chloroquine Analogues: Influence of Side Chain Length and Quinolyl Nitrogen pK_a on Activity vs Chloroquine Resistant Malaria

  摘要：

  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.

  DOI：

  10.1021/jm701478a

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。
• [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：WO2009148659A3

  公开（公告）日：2010-02-25
• SYNTHESIS AND USE OF FLUOROPHORE-TAGGED ANTIMALARIALS
  申请人：National University of Singapore

  公开号：EP2448574A1

  公开（公告）日：2012-05-09
• Synthesis And Use Of Fluorophore-Tagged Antimalarials
  申请人：Lear Martin James

  公开号：US20120100555A1

  公开（公告）日：2012-04-26

  This invention includes a fluorophore-tagged antimalarial represented by the following structural formula (1) or a salt thereof. This invention relates to the synthesis of fluorophore-tagged antimalarials and describes the synthesis of a fluorophore-tagged antimalarial. These fluorophore-tagged antimalarials can be used to image live cells to determine the location of the antimalarial in the cell, identify drug resistance and growth related pathways in Plasmodium isolates, identify new drug targets and chemo-sensitizers to reverse drug resistance.
• [EN] SYNTHESIS AND USE OF FLUOROPHORE-TAGGED ANTIMALARIALS<br/>[FR] SYNTHÈSE ET UTILISATION D'ANTIPALUDÉENS MARQUÉS PAR FLUOROPHORE
  申请人：UNIV SINGAPORE

  公开号：WO2011002415A1

  公开（公告）日：2011-01-06

  This invention includes a fluorophore-tagged antimalarial represented by the following structural formula (1) or a salt thereof. This invention relates to the synthesis of fluorophore-tagged antimalarials and describes the synthesis of a fluorophore-tagged antimalarial. These fluorophore-tagged antimalarials can be used to image live cells to determine the location of the antimalarial in the cell, identify drug resistance and growth related pathways in Plasmodium isolates, identify new drug targets and chemo-sensitizers to reverse drug resistance.