piperidine-3-carboxylic acid [1(S)-(3,4-dibenzyloxy-5-oxo-2,5-dihydrofuran-2(R)-yl)-2-bromoethyl] ester | 798576-80-4

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: piperidine-3-carboxylic acid [1(S)-(3,4-dibenzyloxy-5-oxo-2,5-dihydrofuran-2(R)-yl)-2-bromoethyl] ester
• CAS: 798576-80-4
• 化学式: C₂₆H₂₈BrNO₆
• 分子量: 530.415
• InChiKey: AMSSPPGHXNDBTL-JTGIGXABSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.86
• 重原子数：
  34.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  83.09
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  piperidine-3-carboxylic acid [1(S)-(3,4-dibenzyloxy-5-oxo-2,5-dihydrofuran-2(R)-yl)-2-bromoethyl] ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 以30%的产率得到piperidine-(3R,S)-carboxylic acid-3-[(2R)-2-(3,4-dihydroxy-5-oxo-2,5-dihydrofuran-2-yl)-(2S)-2-bromo-ethyl] 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
• 作为产物：
  描述：

  6-bromo-2,3-di-O-benzyl-L-ascorbic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 piperidine-3-carboxylic acid [1(S)-(3,4-dibenzyloxy-5-oxo-2,5-dihydrofuran-2(R)-yl)-2-bromoethyl] 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