(+/-)-Threo-Ifenprodil

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (+/-)-Threo-Ifenprodil
• 英文别名: rac-threo-2-(4-benzylpiperidin-1-yl)-1-(4-hydroxyphenyl)propan-1-ol；(1RS,2RS)-4-[2-(4-benzylpiperidin-1-yl)-1-hydroxypropyl]phenol；ifenprodil；rac-threo-ifenprodil；4-[(1S,2S)-2-(4-Benzyl-piperidin-1-yl)-1-hydroxy-propyl]-phenol；4-[(1S,2S)-2-(4-benzylpiperidin-1-yl)-1-hydroxypropyl]phenol
• 化学式: C₂₁H₂₇NO₂
• 分子量: 325.451
• InChiKey: UYNVMODNBIQBMV-HRAATJIYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  43.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  苯酚 在 lithium aluminium tetrahydride 、 三氟甲磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.25h， 生成 (+/-)-Threo-Ifenprodil
  参考文献：
  名称：

  Ifenprodil立体异构体：合成，绝对构型以及与生物活性的相关性

  摘要：

  艾芬地尔（1）是一种强效GluN2B选择性Ñ甲基d被用作血管舒张剂脑和临床试验已经研究了用于药物成瘾，特发性肺纤维化，和COVID-治疗天冬氨酸（NMDA）受体拮抗剂19 为了使生物学数据与构型相关联，通过非对映选择性还原并随后通过手性HPLC分离对映异构体来制备所有四种艾芬地尔立体异构体。的立体异构体艾芬地尔的绝对构型由（1 X射线晶体结构分析来确定- [R，2小号- ）1A和（1小号，2小号） - 1D。评估了GluN2B亲和力，离子通道抑制活性以及对α，σ和5-HT受体的选择性。（1 - [R，2 - [R）-Ifenprodil（（1 - [R，2 - [R ）- 1C），发现其朝GluN2B-NMDA受体具有最高的亲和力（ķ我= 5.8纳米）和高抑制离子通量的在双电极电压钳实验（ IC 50 = 223 nM）。尽管该构型不会显着影响GluN2B-NMDA受体的结合，但是（1R）-构型对于提高抑制活性至关重要。（1

  DOI：

  10.1021/acs.jmedchem.0c01912

文献信息

• An Easy Entry to (1S, 2S) and (1R, 2R)-<i>Threo</i>-Ifenprodil
  作者：Sergio Mantegani、Emanuele Arlandini、Enzo Brambilla、Paolo Cremonesi、Mario Varasi

  DOI：10.1080/00397910008087268

  日期：2000.10

  Abstract A facile and practical synthesis of enantiomerically pure (L) or (D)-threo-Ifenprodil was accomplished from (1S, 2S)- and (1R, 2R)-threo-1-(p-nitrophenyl)-2-amino-propan-1, 3-diol via 3-phenylthio derivatives followed by Raney nickel reduction and conversion of the aromatic amine into phenol.

  摘要 从 (1S, 2S)- 和 (1R, 2R)-threo-1-(p-nitrophenyl)-2-amino- 完成对映体纯 (L) 或 (D)-threo-Ifenprodil 的简便实用的合成。 propan-1, 3-diol 通过 3-phenylthio 衍生物，然后 Raney 镍还原和芳香胺转化为苯酚。
• Separation of .alpha.1-adrenergic and N-methyl-D-aspartate antagonist activity in a series of ifenprodil compounds
  作者：B. L. Chenard、I. A. Shalaby、B. K. Koe、R. T. Ronau、T. W. Butler、M. A. Prochniak、A. W. Schmidt、C. B. Fox

  DOI：10.1021/jm00114a018

  日期：1991.10

  Ifenprodil (1) represents a new class of N-methyl-D-aspartate (NMDA) antagonist. This drug also possesses potent activity at several other brain receptors (most notably alpha-1 adrenergic receptors). We have prepared the enantiomers and diastereomers of ifenprodil along with a series of partial structures in order to explore the basic structure activity relations within this class of compounds. From this study, it is clear that alpha-1 adrenergic and NMDA receptor activities may be separated by selection of the threo relative stereochemistry. Examination of the optical isomers of threo-ifenprodil (2) reveals that no further improvement in receptor selectivity is gained from either antipode. Individual removal of most of the structural fragments from the ifenprodil molecule generally results in less active compounds although fluorinated derivative 9 with threo relative stereochemistry is somewhat more potent and substantially more selective for the NMDA receptor. Finally a minimum structure for activity in this series (14) has been identified. This stripped-down version of ifenprodil possesses nearly equivalent affinity for the NMDA receptor with no selectivity over alpha-1 adrenergic receptors.
• KEHGASAVA, KADZUO;XIRAGIKI, MINEHDZI;ADZUMA, NAGATOSI;KOXAGISAVA, TOSITAK+
  作者：KEHGASAVA, KADZUO、XIRAGIKI, MINEHDZI、ADZUMA, NAGATOSI、KOXAGISAVA, TOSITAK+

  DOI：——

  日期：——
• Ifenprodil Stereoisomers: Synthesis, Absolute Configuration, and Correlation with Biological Activity
  作者：Elena Bechthold、Julian A. Schreiber、Kirstin Lehmkuhl、Bastian Frehland、Dirk Schepmann、Freddy A. Bernal、Constantin Daniliuc、Inés Álvarez、Cristina Val Garcia、Thomas J. Schmidt、Guiscard Seebohm、Bernhard Wünsch

  DOI：10.1021/acs.jmedchem.0c01912

  日期：2021.1.28

  COVID-19. To correlate biological data with configuration, all four ifenprodil stereoisomers were prepared by diastereoselective reduction and subsequent separation of enantiomers by chiral HPLC. The absolute configuration of ifenprodil stereoisomers was determined by X-ray crystal structure analysis of (1R,2S)-1a and (1S,2S)-1d. GluN2B affinity, ion channel inhibitory activity, and selectivity over

  艾芬地尔（1）是一种强效GluN2B选择性Ñ甲基d被用作血管舒张剂脑和临床试验已经研究了用于药物成瘾，特发性肺纤维化，和COVID-治疗天冬氨酸（NMDA）受体拮抗剂19 为了使生物学数据与构型相关联，通过非对映选择性还原并随后通过手性HPLC分离对映异构体来制备所有四种艾芬地尔立体异构体。的立体异构体艾芬地尔的绝对构型由（1 X射线晶体结构分析来确定- [R，2小号- ）1A和（1小号，2小号） - 1D。评估了GluN2B亲和力，离子通道抑制活性以及对α，σ和5-HT受体的选择性。（1 - [R，2 - [R）-Ifenprodil（（1 - [R，2 - [R ）- 1C），发现其朝GluN2B-NMDA受体具有最高的亲和力（ķ我= 5.8纳米）和高抑制离子通量的在双电极电压钳实验（ IC 50 = 223 nM）。尽管该构型不会显着影响GluN2B-NMDA受体的结合，但是（1R）-构型对于提高抑制活性至关重要。（1