3-(benzyloxy)-1-(2-(7-chloroquinolin-4-ylamino)ethyl)-2-methylpyridin-4(1H)-one | 1420870-74-1

• 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: 3-(benzyloxy)-1-(2-(7-chloroquinolin-4-ylamino)ethyl)-2-methylpyridin-4(1H)-one
• 英文别名: 1-[2-[(7-Chloroquinolin-4-yl)amino]ethyl]-2-methyl-3-phenylmethoxypyridin-4-one；1-[2-[(7-chloroquinolin-4-yl)amino]ethyl]-2-methyl-3-phenylmethoxypyridin-4-one
• CAS: 1420870-74-1
• 化学式: C₂₄H₂₂ClN₃O₂
• 分子量: 419.911
• InChiKey: XRZRKCCRWOKGBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  30
• 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：
  54.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(benzyloxy)-1-(2-(7-chloroquinolin-4-ylamino)ethyl)-2-methylpyridin-4(1H)-one 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 1-[2-[(7-Chloroquinolin-4-yl)amino]ethyl]-3-hydroxy-2-methylpyridin-4-one
  参考文献：
  名称：

  Synthesis, Antiplasmodial Activity, and β-Hematin Inhibition of Hydroxypyridone–Chloroquine Hybrids

  摘要：

  A series of noncytotoxic 4-aminoquinoline-3-hydroxypyridin-4-one hybrids were synthesized on the basis of a synergistic in vitro combination of a precursor N-alkyl-3-hydroxypyridin-4-one with chloroquine (CQ) and tested in vitro against CO resistant (K1 and W2). an sensitive (3D7) strains of Plasmodium falciparum. In vitro antiplasmodial activity of the precursors was negated by blocking the chelator moiety Via complexation with gallium(III) or benzyl protection. None of the precursors inhibited beta-hematin formation. Most hybrids were more potent inhibitors of beta-hematin formation than CQ and a correlation between antiplasmodial activity and inhibition of beta-hematin formation was observed. Potent hybrids against K1, 3D7, and W2, respectively, were 8c (0.13, 0.004, and 0.1 mu M); 8d (0.08, 0.01, and 0.02 mu M); and 7g (0.07, 0.03, and 0.08 mu M).

  DOI：

  10.1021/ml4001084
• 作为产物：
  描述：

  麦芽醇 在 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 18.0h， 生成 3-(benzyloxy)-1-(2-(7-chloroquinolin-4-ylamino)ethyl)-2-methylpyridin-4(1H)-one
  参考文献：
  名称：

  Conjugation to 4-aminoquinoline improves the anti-trypanosomal activity of Deferiprone-type iron chelators

  摘要：

  Iron is an essential growth component in all living organisms and plays a central role in numerous biochemical processes due to its redox potential and high affinity for oxygen. The use of iron chelators has been suggested as a novel therapeutic approach towards parasitic infections, such as malaria, sleeping sickness and leishmaniasis. Known iron chelating agents such as Deferoxamine and the 3-hydroxypyridin-4-one (HPO) Deferiprone possess anti-parasitic activity but suffer from mammalian toxicity, relatively modest potency, and/or poor oral availability. In this study, we have developed novel derivatives of Deferiprone with increased anti-parasitic activity and reduced cytotoxicity against human cell lines. Of particular interest are several new derivatives in which the HPO scaffold has been conjugated, via a linker, to the 4-aminoquinoline ring system present in the known anti-malaria drug Chloroquine. We report the inhibitory activity of these novel analogues against four parasitic protozoa, Trypanosoma brucei, Trypanosoma cruzi, Leishmania infantum and Plasmodium falciparum, and, for direct comparison, against human cells lines. We also present data, which support the hypothesis that iron starvation is the major cause of growth inhibition of these new Deferiprone-Chloroquine conjugates in T. brucei. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.009

文献信息

• Conjugation to 4-aminoquinoline improves the anti-trypanosomal activity of Deferiprone-type iron chelators
  作者：Sebastian S. Gehrke、Erika G. Pinto、Dietmar Steverding、Karin Pleban、Andre G. Tempone、Robert C. Hider、Gerd K. Wagner

  DOI：10.1016/j.bmc.2012.11.009

  日期：2013.2

  Iron is an essential growth component in all living organisms and plays a central role in numerous biochemical processes due to its redox potential and high affinity for oxygen. The use of iron chelators has been suggested as a novel therapeutic approach towards parasitic infections, such as malaria, sleeping sickness and leishmaniasis. Known iron chelating agents such as Deferoxamine and the 3-hydroxypyridin-4-one (HPO) Deferiprone possess anti-parasitic activity but suffer from mammalian toxicity, relatively modest potency, and/or poor oral availability. In this study, we have developed novel derivatives of Deferiprone with increased anti-parasitic activity and reduced cytotoxicity against human cell lines. Of particular interest are several new derivatives in which the HPO scaffold has been conjugated, via a linker, to the 4-aminoquinoline ring system present in the known anti-malaria drug Chloroquine. We report the inhibitory activity of these novel analogues against four parasitic protozoa, Trypanosoma brucei, Trypanosoma cruzi, Leishmania infantum and Plasmodium falciparum, and, for direct comparison, against human cells lines. We also present data, which support the hypothesis that iron starvation is the major cause of growth inhibition of these new Deferiprone-Chloroquine conjugates in T. brucei. (C) 2012 Elsevier Ltd. All rights reserved.
• Synthesis, Antiplasmodial Activity, and β-Hematin Inhibition of Hydroxypyridone–Chloroquine Hybrids
  作者：Warren A. Andayi、Timothy J. Egan、Jiri Gut、Philip J. Rosenthal、Kelly Chibale

  DOI：10.1021/ml4001084

  日期：2013.7.11

  A series of noncytotoxic 4-aminoquinoline-3-hydroxypyridin-4-one hybrids were synthesized on the basis of a synergistic in vitro combination of a precursor N-alkyl-3-hydroxypyridin-4-one with chloroquine (CQ) and tested in vitro against CO resistant (K1 and W2). an sensitive (3D7) strains of Plasmodium falciparum. In vitro antiplasmodial activity of the precursors was negated by blocking the chelator moiety Via complexation with gallium(III) or benzyl protection. None of the precursors inhibited beta-hematin formation. Most hybrids were more potent inhibitors of beta-hematin formation than CQ and a correlation between antiplasmodial activity and inhibition of beta-hematin formation was observed. Potent hybrids against K1, 3D7, and W2, respectively, were 8c (0.13, 0.004, and 0.1 mu M); 8d (0.08, 0.01, and 0.02 mu M); and 7g (0.07, 0.03, and 0.08 mu M).