23210-56-2

Usage

Originator

Vadilex,Carriere,France,1972

Uses

Different sources of media describe the Uses of 23210-56-2 differently. You can refer to the following data:
1. Ifenprodil is a NMDA receptor antagonist.
2. vasodilator

Manufacturing Process

The initial steps involve reacting benzyl chloride with 4- hydroxypropiophenone. The benzyloxypropiophene thus obtained is first brominated and then reacted with 4-benzylpiperidine to give 1-(pbenzyloxyphenyl)-2-(4-benzyl-piperidino)propan-1-one. The neutral tartrate may be prepared directly by reduction of 1-(pbenzyloxyphenyl)-2-(4-benzyl-piperidino)propan-1-one. For the reduction, a mixture of 175 g of ketone (0.425 mol) and 32 g of tartaric acid (0.213 mol) is hydrogenated at 50°C under pressure of 50 kg/cm2 in 440 ml of methanol in the presence of 12 g of palladium on charcoal. The catalyst is filtered off at elevated temperature, and the filtrate is concentrated by evaporation under reduced pressure to a volume of 300 ml and added in a thin stream to 2.5 liters of diethyl ether with mechanical agitation. The precipitate is separated, washed with diethyl ether and dried in vacuo at 80° to 85°C for several hours. 325 g (96% yield) of the neutral tartrate of 1-(p-hydroxyphenyl)-2-(4-benzyl-piperidino)propan-1-ol are obtained.

Therapeutic Function

Vasodilator

Biological Activity

NMDA receptor antagonist, acting at the polyamine site. Also an α -adrenergic vasodilator. σ 2 ligand displaying about 3-fold selectivity over σ 1 sites.

InChI:InChI=1/2C21H27NO2.C4H6O6/c2*1-16(21(24)19-7-9-20(23)10-8-19)22-13-11-18(12-14-22)15-17-5-3-2-4-6-17;5-1(3(7)8)2(6)4(9)10/h2*2-10,16,18,21,23-24H,11-15H2,1H3;1-2,5-6H,(H,7,8)(H,9,10)

Upstream product

• 2116-65-6 4-benzyl pyridine 
• 70-70-2 4-hydroxypropiophenone 
• 31252-42-3 4-benzylpyperidine 
• 74991-32-5 (RS)-2-(4-benzylpiperidin-1-yl)-1-(4-hydroxyphenyl)propan-1-one 
• 108-95-2 phenol 
• 53946-87-5 2-bromo-(4'-hydroxyphenyl)-propan-1-one 
• 35081-45-9 1-<4-(benzyloxy)phenyl>-2-bromo-1-propanone 
• 35133-39-2 1-(4-(benzyloxy)phenyl)-2-(4-benzylpiperidin-1-yl)propan-1-one 
• 74991-35-8 (1R,2S)-1-(4-Benzyloxy-phenyl)-2-(4-benzyl-piperidin-1-yl)-propan-1-ol 
• 74991-35-8 (1R,2R)-1-(4-(benzyloxy)phenyl)-2-(4-benzylpiperidin-1-yl)propan-1-ol 

Downstream Products

• 35133-55-2 2-(4-benzyl-piperidin-1-yl)-1-(4-methoxy-phenyl)-propan-1-ol 

Relevant academic research and scientific papers

Ifenprodil Stereoisomers: Synthesis, Absolute Configuration, and Correlation with Biological Activity

Ifenprodil (1) is a potent GluN2B-selective N-methyl-d-aspartate (NMDA) receptor antagonist that is used as a cerebral vasodilator and has been examined in clinical trials for the treatment of drug addiction, idiopathic pulmonary fibrosis, and 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 α, σ, and 5-HT receptors were evaluated. (1R,2R)-Ifenprodil ((1R,2R)-1c) showed the highest affinity toward GluN2B-NMDA receptors (Ki = 5.8 nM) and high inhibition of ion flux in two-electrode voltage clamp experiments (IC50 = 223 nM). Whereas the configuration did not influence considerably the GluN2B-NMDA receptor binding, (1R)-configuration is crucial for elevated inhibitory activity. (1R,2R)-Configured ifenprodil (1R,2R)-1c exhibited high selectivity for GluN2B-NMDA receptors over adrenergic, serotonergic, and σ1 receptors.

Method for preventing dyskinesias

Dyskinesias in humans are prevented by administering a therapeutically effective dose of a NR1A/2B site-selective NMDA receptor antagonist compound to a human.

Method for treating diseased-related or drug-induced dyskinesias

Dyskinesias in humans are treated by administering a therapeutically effective dose of an NR1A/2B site-selective NMDA receptor antagonist compound to a human suffering therefrom.

Separation of α1 Adrenergic and N-Methyl-D-aspartate Antagonist Activity in a Series of Ifenprodil Compounds

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 α1 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 α1 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 α1 adrenergic receptors.

Process for the preparation of 1-(4-hydroxyphenyl)-2-(4-benzylpiperidino)-1-propanol and acid-addition salts thereof

A process for the preparation of 1-(4-hydroxyphenyl)-2-(4-benzylpiperidino)-1-propanol (i.e. ifenprodil) and acid-addition salts thereof, characterized by brominating 4'-hydroxypropiophenone in a single or mixed solvent selected from the group consisting of methanol, ethanol and a saturated aliphatic ether, removing hydrogen bromide formed in the course of the bromination, adding 4-benzylpyridine to the reaction mixture, heating the reaction mixture under reflux in a single or mixed solvent selected from the group consisting of methanol and ethanol, and then subjecting the resultant reaction mixture to catalytic reduction to form 1-(4-hydroxyphenyl)-2-(4-benzylpiperidino)-1-propanol hydrobromide in the reaction mixture. The end product (i.e. ifenprodil) can be obtained according to this process in a high yield of about 80% within 14 hours from the starting material in a single reaction container throughout the process, without introducing a protective benzyl group into the starting material prior to the bromination.

THE STEREOSELECTIVE REDUCTION OF α-AMINOPROPIOPHENONE DERIVATIVES WITH SODIUM BOROHYDRIDE

The ratio of erythro and threo products from the sodium borohydride reduction of the hydrochlorides, and other acid salts, of α-aminopropiophenone derivatives was determined.It was found that this procedure resulted in stereoselective formation of erythro-2-amino-1-phenylpropanols in contrast to sodium borohydride reduction of the corresponding free bases.The method was successfully applied to the synthesis of dl-erythro-2-(4-benzylpiperidino)-1-(4-hydroxyphenyl)propanol which has been used as a vasodilator.