4-hydroxyquinoline-2-carboxylic acid [2-(3,4-dihydroxy-5-oxo-2,5-dihydrofuran-2(R)-yl)-2(S)-hydroxyethyl] ester

• 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: 4-hydroxyquinoline-2-carboxylic acid [2-(3,4-dihydroxy-5-oxo-2,5-dihydrofuran-2(R)-yl)-2(S)-hydroxyethyl] ester
• 英文别名: [(2S)-2-[(2R)-3,4-dihydroxy-5-oxo-2H-furan-2-yl]-2-hydroxyethyl] 4-oxo-1H-quinoline-2-carboxylate
• 化学式: C₁₆H₁₃NO₈
• 分子量: 347.281
• InChiKey: QREHQUOSLRHNKG-SMDDNHRTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  142
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  犬尿喹酸 在 palladium on activated charcoal 4-二甲氨基吡啶 、 sodium hydroxide 、 硫酸 、 氢气 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 4-hydroxyquinoline-2-carboxylic acid [2-(3,4-dihydroxy-5-oxo-2,5-dihydrofuran-2(R)-yl)-2(S)-hydroxyethyl] ester
  参考文献：
  名称：

  Design, synthesis and in vitro evaluation on HRPE cells of ascorbic and 6-bromoascorbic acid conjugates with neuroactive molecules

  摘要：

  Preliminary investigations allowed us to anticipate that conjugation of nipecotic acid with L-ascorbate (AA) gave a prodrug endowed with anticonvulsant activity in mice. In view of these results, and in order to get deepen insight into the molecular aspects at the base of the transport mechanism, a second generation of compounds, based on 6-bromo-6-deoxy-L-ascorbic acid (BrAA) as the carrier molecule was designed and synthesized. Effects of the chirality of the transported drug was also investigated on R- and S-nipecotic acid. Interaction and uptake modalities were evaluated in our in vitro model based on human retinal pigment epithelium cells (HRPE), which expresses the membrane L-ascorbic acid (AA) SVCT2 transporters. A remarkable increase on SVCT2 affinity was found going from AA to BrAA conjugates, that is, 11 (K-i = 1187 +/- 78 muM) versus 19 (K-i = 193 +/- 14 muM) and 12 (K-i = 39.8 +/- 3.2 muM) versus 20, (K-i = 7.4 +/- 0.8 muM). Taken together, these data are in agreement with our initial hypothesis on the possibility to achieve better affinities by conjugation with AA analogs, and also consent to hypothesize the presence of accessory interactions that may improve transporters recognition. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.07.043

文献信息

• Design, Synthesis and Activity of Ascorbic Acid Prodrugs of Nipecotic, Kynurenic and Diclophenamic Acids, Liable to Increase Neurotropic Activity
  作者：Stefano Manfredini、Barbara Pavan、Silvia Vertuani、Martina Scaglianti、Donatello Compagnone、Carla Biondi、Angelo Scatturin、Sergio Tanganelli、Luca Ferraro、Puttur Prasad、Alessandro Dalpiaz

  DOI：10.1021/jm015556r

  日期：2002.1.1

  To improve the entry of certain drugs into brain, ascorbic acid (AA) conjugates of these drugs were synthesized and their capacity to interact with SVCT2 ascorbate transporters was explored. Kinetic studies clearly indicate that all of the conjugates were able to competitively inhibit ascorbate transport in human retinal pigment epithelial cells (HRPE). In vivo studies, in a mouse model system, demonstrate that conjugate 3 is better absorbed compared to the nonconjugated parent drug.
• Design, synthesis and in vitro evaluation on HRPE cells of ascorbic and 6-bromoascorbic acid conjugates with neuroactive molecules
  作者：Stefano Manfredini、Silvia Vertuani、Barbara Pavan、Federica Vitali、Martina Scaglianti、Fabrizio Bortolotti、Carla Biondi、Angelo Scatturin、Puttur Prasad、Alessandro Dalpiaz

  DOI：10.1016/j.bmc.2004.07.043

  日期：2004.10

  Preliminary investigations allowed us to anticipate that conjugation of nipecotic acid with L-ascorbate (AA) gave a prodrug endowed with anticonvulsant activity in mice. In view of these results, and in order to get deepen insight into the molecular aspects at the base of the transport mechanism, a second generation of compounds, based on 6-bromo-6-deoxy-L-ascorbic acid (BrAA) as the carrier molecule was designed and synthesized. Effects of the chirality of the transported drug was also investigated on R- and S-nipecotic acid. Interaction and uptake modalities were evaluated in our in vitro model based on human retinal pigment epithelium cells (HRPE), which expresses the membrane L-ascorbic acid (AA) SVCT2 transporters. A remarkable increase on SVCT2 affinity was found going from AA to BrAA conjugates, that is, 11 (K-i = 1187 +/- 78 muM) versus 19 (K-i = 193 +/- 14 muM) and 12 (K-i = 39.8 +/- 3.2 muM) versus 20, (K-i = 7.4 +/- 0.8 muM). Taken together, these data are in agreement with our initial hypothesis on the possibility to achieve better affinities by conjugation with AA analogs, and also consent to hypothesize the presence of accessory interactions that may improve transporters recognition. (C) 2004 Elsevier Ltd. All rights reserved.