1-(4-aminobutyl)-3-(benzyloxy)-2-methylpyridin-4(1H)-one | 1132878-61-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-aminobutyl)-3-(benzyloxy)-2-methylpyridin-4(1H)-one
• 英文别名: 1-(4-Aminobutyl)-2-methyl-3-phenylmethoxypyridin-4-one；1-(4-aminobutyl)-2-methyl-3-phenylmethoxypyridin-4-one
• CAS: 1132878-61-5
• 化学式: C₁₇H₂₂N₂O₂
• 分子量: 286.374
• InChiKey: VCGLYTZWHIGIHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-aminobutyl)-3-(benzyloxy)-2-methylpyridin-4(1H)-one 在 硫酸 、 palladium 10% on activated carbon 、 N,N'-羰基二咪唑 、 锌 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 17.0h， 生成 2-(3-benzoylphenyl)-N-(4-(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)butyl)propanamide
  参考文献：
  名称：

  一系列铁和铜螯合去铁酮衍生物作为抗白色念珠菌的新药剂的设计、合成和生物学评价

  摘要：

  白色念珠菌在特定条件下会导致严重的侵袭性系统性念珠菌病，这与其在生物和人造表面产生生物膜的能力有关。许多研究报告了铁在真菌生长和毒力中的作用以及金属螯合剂干扰白色念珠菌代谢、毒力和生物膜形成的能力。 在这里，我们报告了 3-羟基-1,2-二甲基-4(1 H )-吡啶酮（去铁酮）衍生物对白色念珠菌浮游细胞和生物膜的活性。一些研究的化合物（2b和3b）能够螯合 Fe(III) 和 Cu(II)，并对浮游细胞（MIC 50 分别为 32 μg/mL 和 16 μg/mL）和生物膜显示出有趣的活性在培养的 ATCC 10231白色念珠菌中形成（BMIC 50 分别为 32 μg/mL 和 16 μg/mL）；通过向培养基中添加 Fe(III) 和 Cu(II)，这种活性以浓度依赖的方式降低。此外，活性最强的化合物3b对Galleria mellonella幼虫。

  DOI：

  10.1016/j.bmcl.2021.128087
• 作为产物：
  描述：

  麦芽醇 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 24.0h， 生成 1-(4-aminobutyl)-3-(benzyloxy)-2-methylpyridin-4(1H)-one
  参考文献：
  名称：

  一系列铁和铜螯合去铁酮衍生物作为抗白色念珠菌的新药剂的设计、合成和生物学评价

  摘要：

  白色念珠菌在特定条件下会导致严重的侵袭性系统性念珠菌病，这与其在生物和人造表面产生生物膜的能力有关。许多研究报告了铁在真菌生长和毒力中的作用以及金属螯合剂干扰白色念珠菌代谢、毒力和生物膜形成的能力。 在这里，我们报告了 3-羟基-1,2-二甲基-4(1 H )-吡啶酮（去铁酮）衍生物对白色念珠菌浮游细胞和生物膜的活性。一些研究的化合物（2b和3b）能够螯合 Fe(III) 和 Cu(II)，并对浮游细胞（MIC 50 分别为 32 μg/mL 和 16 μg/mL）和生物膜显示出有趣的活性在培养的 ATCC 10231白色念珠菌中形成（BMIC 50 分别为 32 μg/mL 和 16 μg/mL）；通过向培养基中添加 Fe(III) 和 Cu(II)，这种活性以浓度依赖的方式降低。此外，活性最强的化合物3b对Galleria mellonella幼虫。

  DOI：

  10.1016/j.bmcl.2021.128087

文献信息

• New deferiprone derivatives as multi-functional cholinesterase inhibitors: design, synthesis and in vitro evaluation
  作者：Martina Bortolami、Fabiana Pandolfi、Daniela De Vita、Camilla Carafa、Antonella Messore、Roberto Di Santo、Marta Feroci、Roberta Costi、Isabella Chiarotto、Donatella Bagetta、Stefano Alcaro、Marisa Colone、Annarita Stringaro、Luigi Scipione

  DOI：10.1016/j.ejmech.2020.112350

  日期：2020.7

  for Alzheimer's disease, a series of deferiprone derivatives has been synthesized and evaluated in vitro with the hypothesis that they can restore the cholinergic tone and attenuate the dyshomeostasis of the metals mainly involved in the pathology. These compounds were designed as dual binding site AChE inhibitors: they possess an arylalkylamine moiety connected via an alkyl chain to a 3-hydroxy-4-pyridone

  为了获得用于阿尔茨海默氏病的多功能分子，已经合成了一系列去铁酮衍生物，并在体外进行了评估，其假设是它们可以恢复胆碱能的基调并减轻主要参与病理学的金属的动态平衡。这些化合物被设计为双结合位点AChE抑制剂：它们具有通过烷基链连接至3-羟基-4-吡啶酮片段的芳基烷基胺部分，以允许与催化活性位点（CAS）和外围阴离子位点（PAS）同时相互作用）的酶。将去铁酮部分和2-氨基吡啶，2-氨基嘧啶或2,4-二氨基嘧啶基团掺入这些化合物中，为了获得潜在的能够螯合在Aβ斑块中共存并参与自由基种类生成的生物金属的分子。使用Ellman方法通过对EeAChE和eqBChE的酶抑制研究来测试合成的化合物。最有效的EeAChE抑制剂是化合物5a，Ki为788±51 nM，而最有效的eqBChE抑制剂是化合物12和19，Ki值分别为182±18 nM和258±25 nM。在最有效的胆碱酯酶抑制剂中，选定的化合物能够与
• Salmonella Typhimurium and Pseudomonas aeruginosa Respond Differently to the Fe Chelator Deferiprone and to Some Novel Deferiprone Derivatives
  作者：Serena Ammendola、Valerio Secli、Francesca Pacello、Martina Bortolami、Fabiana Pandolfi、Antonella Messore、Roberto Di Santo、Luigi Scipione、Andrea Battistoni

  DOI：10.3390/ijms221910217

  日期：——

  The ability to obtain Fe is critical for pathogens to multiply in their host. For this reason, there is significant interest in the identification of compounds that might interfere with Fe management in bacteria. Here we have tested the response of two Gram-negative pathogens, Salmonella enterica serovar Typhimurium (STM) and Pseudomonas aeruginosa (PAO1), to deferiprone (DFP), a chelating agent already in use for the treatment of thalassemia, and to some DFP derivatives designed to increase its lipophilicity. Our results indicate that DFP effectively inhibits the growth of PAO1, but not STM. Similarly, Fe-dependent genes of the two microorganisms respond differently to this agent. DFP is, however, capable of inhibiting an STM strain unable to synthesize enterochelin, while its effect on PAO1 is not related to the capability to produce siderophores. Using a fluorescent derivative of DFP we have shown that this chelator can penetrate very quickly into PAO1, but not into STM, suggesting that a selective receptor exists in Pseudomonas. Some of the tested derivatives have shown a greater ability to interfere with Fe homeostasis in STM compared to DFP, whereas most, although not all, were less active than DFP against PAO1, possibly due to interference of the added chemical tails with the receptor-mediated recognition process. The results reported in this work indicate that DFP can have different effects on distinct microorganisms, but that it is possible to obtain derivatives with a broader antimicrobial action.

  获得铁元素对于病原体在宿主体内繁殖至关重要。因此，人们对于寻找可能干扰细菌铁元素管理的化合物具有重大兴趣。在此，我们测试了两种革兰氏阴性病原菌沙门氏菌鼠伤寒沙门氏菌（STM）和铜绿假单胞菌（PAO1）对于去铁酮（DFP）（一种已经用于治疗地中海贫血的螯合剂）及其一些增加亲脂性的衍生物的反应。我们的结果表明，DFP有效抑制PAO1的生长，但不抑制STM的生长。同样，这种药剂对于这两种微生物的铁依赖基因的反应也不同。然而，DFP可以抑制无法合成肠铁素的STM菌株，而其对PAO1的影响与产生铁载体的能力无关。我们使用DFP的荧光衍生物表明，这种螯合剂可以迅速进入PAO1，但不能进入STM，这表明铜绿假单胞菌中存在选择性受体。一些测试的衍生物在干扰STM中的铁元素稳态方面比DFP表现出更强的能力，而大多数（尽管不是全部）对PAO1的活性都低于DFP，可能是由于添加的化学尾与受体介导的识别过程干扰。本研究报告的结果表明，DFP对不同的微生物可能具有不同的影响，但可以获得具有更广泛抗微生物作用的衍生物。
• 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.
• Design, synthesis and biological evaluation of a series of iron and copper chelating deferiprone derivatives as new agents active against Candida albicans
  作者：Martina Bortolami、Fabiana Pandolfi、Antonella Messore、Daniele Rocco、Marta Feroci、Roberto Di Santo、Daniela De Vita、Roberta Costi、Paola Cascarino、Giovanna Simonetti、Luigi Scipione

  DOI：10.1016/j.bmcl.2021.128087

  日期：2021.6

  candidiasis that are related to its ability to produce biofilm on biological and artificial surfaces. Many studies reported the role of iron in fungal growth and virulence and the ability of metal chelating agents to interfere with C. albicans metabolism, virulence and biofilm formation. Here we report the activity of 3-hydroxy-1,2-dimethyl-4(1H)-pyridinone (deferiprone) derivatives against C. albicans planktonic

  白色念珠菌在特定条件下会导致严重的侵袭性系统性念珠菌病，这与其在生物和人造表面产生生物膜的能力有关。许多研究报告了铁在真菌生长和毒力中的作用以及金属螯合剂干扰白色念珠菌代谢、毒力和生物膜形成的能力。 在这里，我们报告了 3-羟基-1,2-二甲基-4(1 H )-吡啶酮（去铁酮）衍生物对白色念珠菌浮游细胞和生物膜的活性。一些研究的化合物（2b和3b）能够螯合 Fe(III) 和 Cu(II)，并对浮游细胞（MIC 50 分别为 32 μg/mL 和 16 μg/mL）和生物膜显示出有趣的活性在培养的 ATCC 10231白色念珠菌中形成（BMIC 50 分别为 32 μg/mL 和 16 μg/mL）；通过向培养基中添加 Fe(III) 和 Cu(II)，这种活性以浓度依赖的方式降低。此外，活性最强的化合物3b对Galleria mellonella幼虫。