1,2-dimethyl-3-hydroxy-4(1H)-pyridinone hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone hydrochloride
• 英文别名: 1,2-Dimethyl-3-hydroxypyridin-4-one hydrochloride；3-hydroxy-1,2-dimethylpyridin-4-one;hydrochloride
• 化学式: C₇H₉NO₂*ClH
• 分子量: 175.615
• InChiKey: QJOJFHDKSGPDBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.82
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  麦芽醇 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 92.0~105.0 ℃ 、400.01 kPa 条件下， 反应 44.0h， 生成 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone hydrochloride
  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

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。
• 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).