3-benzyloxy-1-n-hexyl-2-methyl-4-pyridone | 82756-32-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-benzyloxy-1-n-hexyl-2-methyl-4-pyridone
• 英文别名: 3-(benzyloxy)-1-hexyl-2-methylpyridin-4(1H)-one；1-Hexyl-2-methyl-3-phenylmethoxypyridin-4-one
• CAS: 82756-32-9
• 化学式: C₁₉H₂₅NO₂
• 分子量: 299.413
• InChiKey: MIYGKIIWZMZPAD-UHFFFAOYSA-N

物化性质

• 沸点：
  441.3±45.0 °C(Predicted)
• 密度：
  1.06±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-benzyloxy-1-n-hexyl-2-methyl-4-pyridone 在 氢溴酸 作用下， 以 溶剂黄146 为溶剂， 反应 0.5h， 以70%的产率得到1-己基-3-羟基-2-甲基吡啶-4-酮
  参考文献：
  名称：

  Bartulin, J.; Belmar, J.; Gallardo, H., Journal of Heterocyclic Chemistry, 1992, vol. 29, # 4, p. 1017 - 1019

  摘要：

  DOI：
• 作为产物：
  描述：

  麦芽醇 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 2.5h， 生成 3-benzyloxy-1-n-hexyl-2-methyl-4-pyridone
  参考文献：
  名称：

  设计和合成用于光动力疗法的5-氨基松油酸/ 3-羟基吡啶酮共轭物：增加原卟啉IX的产生和肿瘤细胞的光毒性† ‡

  摘要：

  5-氨基戊酸（ALA）及其衍生物已在光动力疗法（PDT）中广泛用作光敏剂，原卟啉IX（PpIX）的皮肤病学和泌尿科疾病的前体。然而，由于ALA的低生物利用度限制了ALA-PDT，这是由于ALA由于其在生理pH下的两性离子性质而难以被细胞吸收。为了提高治疗效果并诱导更高水平的PpIX，通过ALA与氨基酸结合的ALA与3-羟基吡啶-4-酮（HPO）铁螯合剂的结合，合成了一系列ALA前药。酰胺键。药代动力学研究表明，与单独使用ALA或同时使用ALA和CP94（1,2-二乙基-3-羟基吡啶-4-酮）相比，一种ALA-HPO共轭物可显着增强一系列肿瘤细胞系中PpIX的产生。细胞内的卟啉荧光水平与光照射后的细胞光毒性显示出良好的相关性，表明ALA-HPO偶联物在光动力疗法中的潜在应用。

  DOI：

  10.1039/c6md00040a

文献信息

• Synthesis, physicochemical properties, and biological evaluation of N-substituted 2-alkyl-3-hydroxy-4(1H)-pyridinones: orally active iron chelators with clinical potential
  作者：Paul S. Dobbin、Robert C. Hider、Adrian D. Hall、Paul D. Taylor、Patience Sarpong、John B. Porter、Gaoyi Xiao、Dick van der Helm

  DOI：10.1021/jm00069a002

  日期：1993.8

  The synthesis of a range of novel bidentate ligands containing the chelating moiety 3-hydroxy-4(1H)-pyridinone is described. The pKa values of the ligands and the stability constants of their iron(III) complexes have been determined. The crystal structures of one of the ligands and one of the iron(III) complexes are presented. The distribution coefficients of the ligands are reported and are related

  描述了一系列包含螯合部分3-羟基-4（1H）-吡啶酮的新型双齿配体的合成。已经确定了配体的pKa值及其铁（III）配合物的稳定性常数。给出了一种配体和一种铁（III）配合物的晶体结构。报告了配体的分布系数，并且与配体从肝细胞中去除铁的能力有关。描述了3-羟基-4（1H）-吡啶酮对细胞氧化损伤的影响。与目前的铁螯合剂去铁胺-B相比，本研究中描述的许多双齿配体在铁超载小鼠中具有口服活性。
• Inhibitor development for 4-hydroxyphenylpyruvate dioxygenase, employing tyrosinemia 1 as a model for human diseases mediated by 2-oxoacid utilizing dioxygenases
  申请人：Hanauske-Abel M. Hartmut

  公开号：US20050288187A1

  公开（公告）日：2005-12-29

  The present invention is directed to a method of inhibiting 4-hydroxyphenylpyruvate dioxygenase in a living system by administering to the living system an effective amount of a compound of formulas I or II or III or derivatives thereof as follows: R 1 , R 2 , R 3 , and R 4 each individually represent a hydrogen, an alkyl, alkenyl, or alkoxy group containing 1 to about 8 carbon atoms, an aryl, aralkyl, or cycloalkyl group containing about 5 to 12 carbon atoms, or a carboalkoxy or carbamyl group containing up to 8 carbon atoms, or a peptide or peptidomimetic moiety containing 10 to about 30 carbon atoms under conditions effective to inhibit 4-hydroxyphenylpyruvate dioxygenase in the living system. These compounds are also useful in carrying out a method of treating a patient and a method of regulating plant growth.

  本发明涉及通过向生物体内投与式I或II或III或其衍生物的有效量来抑制生物体内4-羟基苯丙酮酸双氧酶的方法，其中：R1，R2，R3和R4分别表示氢，含1至约8个碳原子的烷基，烯基或烷氧基，含约5至12个碳原子的芳基，芳基烷基或环烷基，含多达8个碳原子的羧基烷氧基或氨基甲酰基，或含有10至约30个碳原子的肽或类肽基团，在有效条件下抑制生物体内的4-羟基苯丙酮酸双氧酶。这些化合物还可用于进行治疗患者的方法和调节植物生长的方法。
• Design, Synthesis, and Antimicrobial Evaluation of Hexadentate Hydroxypyridinones with High Iron(III) Affinity
  作者：Ming-Xia Zhang、Chun-Feng Zhu、Ying-Jun Zhou、Xiao-Le Kong、Robert C Hider、Tao Zhou

  DOI：10.1111/cbdd.12358

  日期：2014.12

  A range of hexadentate 3‐hydroxypyridin‐4‐ones (HPOs) with high affinity for iron(III) has been synthesized. The log stability constants of two HPO–iron complexes (logK1) were determined to be over 34, and pFe values of the two HPOs were determined to be over 31. Antimicrobial assay indicated that they are able to markedly inhibit the growth of both Gram‐positive and Gram‐negative bacteria. Compounds 14a and 14e were found to exhibit the strongest inhibitory activity against Staphyloccocus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli, with MIC values of 8, 8, 16, and 8 μg/mL, respectively. These results indicate that hexadentate 3‐hydroxypyridin‐4‐ones have potential application as antimicrobial agents, especially in the treatment of wound infection.
• Bartulin, J.; Belmar, J.; Gallardo, H., Journal of Heterocyclic Chemistry, 1992, vol. 29, # 4, p. 1017 - 1019
  作者：Bartulin, J.、Belmar, J.、Gallardo, H.、Leon, G.

  DOI：——

  日期：——
• Design, synthesis and biological evaluation of 5-aminolaevulinic acid/3-hydroxypyridinone conjugates as potential photodynamic therapeutical agents
  作者：Chun-Feng Zhu、Sinan Battah、Xiaole Kong、Brandon J. Reeder、Robert C. Hider、Tao Zhou

  DOI：10.1016/j.bmcl.2014.12.018

  日期：2015.2

  5-Aminolaevulinic acid (ALA) prodrugs have been widely used in photodynamic therapy (PDT) as precursors to the natural photosensitizer, protoporphyrin IX (PpIX). The main disadvantage of this therapy is that ALA is poorly absorbed by cells due to its high hydrophilicity. In order to improve the therapeutical effect and induce higher yields of PpIX, a range of prodrugs of ALA conjugated to 3-hydroxypyridin4-ones (HPO) were synthesized. Pharmacokinetic studies indicated that some of the ALA-HPO conjugates are more efficient than ALA for PpIX production in the human breast adenocarcinoma cell line (MDA-MB-468). The intracellular porphyrin fluorescence levels showed good correlation with cellular phototoxicity following light exposure, suggesting the potential application of the ALA-HPO conjugates in photodynamic therapy. (C) 2014 Elsevier Ltd. All rights reserved.