ifenprodil | 74991-36-9

• 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: ifenprodil
• 英文别名: (+/-)-Erythro-Ifenprodil；4-[(1R,2S)-2-(4-benzylpiperidin-1-yl)-1-hydroxypropyl]phenol
• CAS: 74991-36-9
• 化学式: C₂₁H₂₇NO₂
• 分子量: 325.451
• InChiKey: UYNVMODNBIQBMV-KKSFZXQISA-N

物化性质

• 熔点：
  197-199 °C (decomp)
• 沸点：
  493.5±30.0 °C(Predicted)
• 密度：
  1.140±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

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：

  4'-苯甲氧基-2-溴苯丙酮 在 palladium on activated charcoal 钾硼氢 、 氢气 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 为溶剂， 生成 ifenprodil
  参考文献：
  名称：

  Separation of .alpha.1-adrenergic and N-methyl-D-aspartate antagonist activity in a series of ifenprodil compounds

  摘要：

  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.

  DOI：

  10.1021/jm00114a018

文献信息

• [EN] 3,3-DIFLUOROPIPERIDINE CARBAMATE HETEROCYCLIC COMPOUNDS AS NR2B NMDA RECEPTOR ANTAGONISTS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES 3,3-DIFLUOROPIPÉRIDINE CARBAMATE UTILISÉS EN TANT QU'ANTAGONISTES DES RÉCEPTEURS NMDA NR2B
  申请人：RUGEN HOLDINGS (CAYMAN) LTD

  公开号：WO2016196513A1

  公开（公告）日：2016-12-08

  Disclosed are chemical entities of Formula (I), wherein R1 and Z are defined herein, as NR2B subtype selective receptor antagonists. Also disclosed are pharmaceutical compositions comprising a chemical entity of Formula (I), and methods of treating various diseases and disorders associated with NR2B antagonism, e.g., diseases and disorders of the CNS, such as depression, by administering a chemical entity of Formula (I).

  本文披露了化学实体的化学式（I），其中R1和Z如本文所定义，作为NR2B亚型选择性受体拮抗剂。还披露了包括化学实体的化学式（I）的药物组合物，以及通过给予化学实体的化学式（I）来治疗与NR2B拮抗作用相关的各种疾病和疾病的方法，例如中枢神经系统疾病和疾病，如抑郁症。
• [EN] DIFLUOROETHYLPYRIDINE DERIVATIVES AS NR2B NMDA RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS DE DIFLUOROÉTHYLPYRIDINE EN TANT QU'ANTAGONISTES DES RÉCEPTEURS NMDA SÉLECTIFS DU SITE NR2B
  申请人：RUGEN HOLDINGS CAYMAN LTD

  公开号：WO2015187845A1

  公开（公告）日：2015-12-10

  Disclosed are chemical entities of formula (I) wherein X, Y, Z, R1, R3, R4, R5 and R6 are defined herein, as NR2B subtype selective receptor antagonists. Also disclosed are pharmaceutical compositions comprising a chemical entity of formula (I), and methods of treating various diseases and disorders associated with NR2B antagonism, e.g., diseases and disorders of the CNS, such as depression, by administering a chemical entity of formula I.

  本文披露了化学实体的结构式（I），其中X、Y、Z、R1、R3、R4、R5和R6的定义如本文所述，作为NR2B亚型选择性受体拮抗剂。还披露了包括结构式（I）的化学实体的药物组合物，以及通过给予结构式I的化学实体治疗与NR2B拮抗作用相关的各种疾病和障碍的方法，例如中枢神经系统的疾病和障碍，如抑郁症。
• [EN] 3,3-DIFLUORO-PIPERIDINE DERIVATIVES AS NR2B NMDA RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS 3,3-DIFLUORO-PIPÉRIDINE EN TANT QU'ANTAGONISTES DES RÉCEPTEURS NMDA NR2B
  申请人：RUGEN HOLDINGS CAYMAN LTD

  公开号：WO2016126869A1

  公开（公告）日：2016-08-11

  Disclosed are chemical entities of Formula (I): wherein X, Y, Z, R1, R3, R4 and R5 are defined herein, as NR2B subtype selective receptor antagonists. Also disclosed are pharmaceutical compositions comprising a chemical entity of Formula (I), and methods of treating various diseases and disorders associated with NR2B antagonism, e.g., diseases and disorders of the CNS, such as depression, by administering a chemical entity of Formula (I).

  公开了化学实体的化学式（I）：其中X、Y、Z、R1、R3、R4和R5如本文所定义，作为NR2B亚型选择性受体拮抗剂。还公开了包括化学实体的化学式（I）的药物组合物，以及通过给予化学实体的化学式（I）来治疗与NR2B拮抗作用相关的各种疾病和疾病的方法，例如中枢神经系统的疾病和疾病，如抑郁症。
• 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
• PYRROLOPYRIMIDINE DERIVATIVES AS NR2B NMDA RECEPTOR ANTAGONISTS
  申请人：Rugen Holdings (Cayman) Limited

  公开号：US20160075713A1

  公开（公告）日：2016-03-17

  Disclosed are chemical entities of formula I: wherein X, Y, Z, R 1 , R 3 , R 4 , R 5 and R 6 are defined herein, as NR2B subtype selective receptor antagonists. Also disclosed are pharmaceutical compositions comprising a chemical entity of formula I, and methods of treating various diseases and disorders associated with NR2B antagonism, e.g., diseases and disorders of the CNS, such as depression, by administering a chemical entity of formula I.

  本文揭示了化学实体的公式I：其中X、Y、Z、R1、R3、R4、R5和R6在此定义为NR2B亚型选择性受体拮抗剂。还揭示了包含化学实体的公式I的药物组合物，并通过给予公式I的化学实体来治疗与NR2B拮抗有关的各种疾病和障碍，例如中枢神经系统的疾病和障碍，如抑郁症。